Solubilization of lipophilic drugs is essential for efficient uptake. We detail the solubilization of imatinib in simulated gastrointestinal fluids containing taurocholate (TC) and lecithin (L) and reflecting fasted versus fed states using NMR spectroscopy, X-ray diffractometry, transmission electron microscopy, and dynamic light scattering analysis. Imatinib concentration impacted colloidal geometries and molecular dynamics in a fasted state. At drug substance concentrations up to 250 μM, imatinib was mainly engulfed within the core of >110 nm in diameter vesicles. At higher drug concentrations, the colloids collapsed to <40 nm, and imatinib migrated into the shell of the micelles, mainly being associated with the lipophilic face of TC but not with L. Simulating the fed state resulted in the formation of small micelles independent of the drug concentration. Furthermore, a hydrogel was formed, effectively keeping the drug substance in an amorphous state even when stressed by drying. In conclusion, this study detailed the fascinating dynamics of colloidal structures and molecular assembly as a function of imatinib concentration in biorelevant conditions. This approach may provide a blueprint for the rational development of future pharmaceutical formulations, taking the molecular interactions with bile salts/phospholipids into account.

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.

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We present ¹⁴N-¹H HMQC MAS NMR experiments in the solid state as a promising tool to study amorphous formulations. Poly(2-oxazoline) based polymer micelles loaded with different amounts of the cancer drug paclitaxel serve to highlight the possibilities offered by these experiments: While the very similar ¹⁵N chemical shifts hamper a solid-state NMR characterization based on this nucleus, ¹⁴N is a very versatile alternative. ¹⁴N-¹H HMQC experiments yield well-separated signals, which are spread over a large ppm range, provide information on the symmetry of the nitrogen environment and probe ¹⁴N-¹H through-space proximities.

~~ and Ionic Diffusion in Lithium Thioborate Glasses 1313Conclusions It has been shown that deuteron NMR is well suited to obtain quantitative informations about the dynamics of the anisotropic reorientational as well as the site exchange motions of molecules specifically sorbed in the voids of zeolites. Intracrystalline diffusion constants can be obtained which compare very well with the data from proton pulsed field gradient measurements in single crystal zeolites (NaX). The 'H-NMR lineshape method applied presently allows to obtain intracrystalline diffusivities in zeolites in practical use, i.e. materials of sizes in the pm range (or even lower) and of rather high paramagnetic impurity levels.Financial support by the ,,Deutsche Forschungsgemeinschaft" and ,,Fonds der Chemischen Industrie" is gratefully acknowledged.'Li NMR spin-lattice relaxation rates at 16 MHz and 117 MHz have been measured at various temperatures for glasses in the non-oxide chalcogenide system B2S3-Li2S-LiX with X = C1, Br, I. As compared with the corresponding oxide glasses these materials are distinguished by a higher ionic conductivity, and the relaxation maxima are better accessible. The relaxation rates display anomalous temperature and frequency dependences. Attempts to interpret the non-BPP-type relaxation in terms of appropriate diffusion models are discussed.