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  - Scheidel, Sebastian
A1  - Östreicher, Laurina
A1  - Mark, Isabelle
A1  - Pöppler, Ann-Christin
T1  - You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning
JF  - Magnetic Resonance in Chemistry
N2  - Although solid-state nuclear magnetic resonance (NMR) is a versatile analytical tool to study polymorphs and phase transitions of pharmaceutical molecules and products, this work summarizes examples of spontaneous and unexpected (and unwanted) structural rearrangements and phase transitions (amorphous-to-crystalline and crystalline-to-crystalline) under magic angle spinning (MAS) conditions, some of them clearly being due to the pressure experienced by the samples. It is widely known that such changes can often be detected by X-ray powder diffraction (XRPD); here, the capability of solid-state NMR experiments with a special focus on \(^{1}\)H-\(^{13}\)C frequency-switched Lee–Goldburg heteronuclear correlation (FSLG HETCOR)/MAS NMR experiments to detect even subtle changes on a molecular level not observable by conventional 1D NMR experiments or XRPD is presented. Furthermore, it is shown that a polymorphic impurity combined with MAS can induce a crystalline-to-crystalline phase transition. This showcases that solid-state NMR is not always noninvasive and such changes upon MAS should be considered in particular when compounds are studied over longer time spans.
KW  - \(^{1}\)H-\(^{13}\)C HETCOR
KW  - API
KW  - structural changes
KW  - XRPD
KW  - solid-state NMR
KW  - MAS
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318838
VL  - 60
IS  - 6
SP  - 572
EP  - 582
ER  - 
TY  - JOUR
A1  - Pöppler, Ann-Christin
A1  - Lübtow, Michael  M.
A1  - Schlauersbach, Jonas
A1  - Wiest, Johannes
A1  - Meinel, Lorenz
A1  - Luxenhofer, Robert
T1  - Loading dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid-State NMR Spectroscopy
JF  - Angewandte Chemie International Edition
N2  - Detailed insight into the internal structure of drug‐loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2‐oxazolines) and poly(2‐oxazines) results in poorer dissolution properties. Using solid‐state NMR spectroscopy and complementary tools we propose a loading‐dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross‐peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh‐loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems.
KW  - dissolution rates
KW  - micelles
KW  - polymers
KW  - short-range order
KW  - solid-state NMR spectroscopy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206705
VL  - 58
IS  - 51
ER  -