¹⁴N–¹H HMQC solid-state NMR as a powerful tool to study amorphous formulations – an exemplary study of paclitaxel loaded polymer micelles

Abstract

14N–1H HMQC experiments are powerful experiments to characterize amorphous drug–polymer formulations of paclitaxel yielding well-separated signals in the 14N dimension as well as information on the symmetry of 14N and 14N–1H interactions.

Drug–Polymer Interactions in Acetaminophen/Hydroxypropylmethylcellulose Acetyl Succinate Amorphous Solid Dispersions Revealed by Multidimensional Multinuclear Solid-State NMR Spectroscopy

“…They enable fast characterization of pharmaceutical compounds and formulation by probing API–polymer interaction, allowing NMR crystallography approaches and understanding of low drug-loaded formulation . The 14 N– 1 H heteronuclear multiple-quantum coherence (HMQC) experiment carried out at the high magnetic field and at ultrafast MAS conditions under direct 1 H signal detection has been robustly employed to probe interactions in crystalline systems , and recently to highlight molecular association and interactions in amorphous dispersions. , 14 N– 1 H HMQC spectra were used to identify hydrogen bonding interaction in a nicotinamide palmitic acid cocrystal and acetaminophen–PVP amorphous dispersion . The versatility of this experiment was demonstrated by providing information on the symmetry of the nitrogen environment and through-space proximities in paclitaxel-loaded polymer micelles amorphous formulations .…”

“…The 14 N– 1 H heteronuclear multiple-quantum coherence (HMQC) experiment carried out at the high magnetic field and at ultrafast MAS conditions under direct 1 H signal detection has been robustly employed to probe interactions in crystalline systems , and recently to highlight molecular association and interactions in amorphous dispersions. , 14 N– 1 H HMQC spectra were used to identify hydrogen bonding interaction in a nicotinamide palmitic acid cocrystal and acetaminophen–PVP amorphous dispersion . The versatility of this experiment was demonstrated by providing information on the symmetry of the nitrogen environment and through-space proximities in paclitaxel-loaded polymer micelles amorphous formulations . The 14 N– 1 H HMQC experiment has however, to the best of our knowledge, not been used so far to investigate API–polymer interactions in HPMC-AS-based amorphous formulations.…”

Poly(2‐oxazoline)‐ and Poly(2‐oxazine)‐Based Self‐Assemblies, Polyplexes, and Drug Nanoformulations—An Update

“…Specifically, 14 N‐ 1 H heteronuclear multiple‐quantum correlation (HMQC) solid‐state NMR was employed to study the interactions of amide groups in polymer and drug molecules. [ 173 ] In comparison to neat polymer and PTX, the formulations exhibited decreasing in 14 N quadrupolar shift at negative values, which suggests a more symmetric nitrogen environment. The authors assigned these spectral changes to the tertiary amides of POx in a close proximity of PTX molecules serving as hydrogen bond acceptors, leading to the more symmetric nitrogen environment.…”

Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs

“…Worm-inhibiting drugs paclitaxel and vismodegib contain numerous electronegative and hydrogen bond-accepting groups that may strengthen their interaction with the poly(2-oxazoline). Notably, NMR spectra previously suggested that paclitaxel can interact with the amide bond motif of both poly(2-methyl-2-oxasoline) and poly(2-butyl-2-oxasoline) [11] . Therefore, such drugs can bind to the same binding sites that RD binds to and may result in the displacement of the dye if their binding affinity exceeds that of RD.…”