Investigation of solubilising effects of bile salts on an active pharmaceutical ingredient with unusual pH dependent solubility by NMR spectroscopy

Applications of NMR diffusion methods with emphasis on ion pairing in inorganic chemistry: a mini‐review

“…The most popular applications involving NMR diffusion methods concern themselves with directly estimating a molecular weight (MW) frequently with the help of model compounds, as indicated in Fig. .…”

“…The published applications concerned with D‐values and MWs cover a wide range of topics including the analysis of various polymer mixtures, muddy sediments and starches . Further, the methods have been used in the quantification of small molecules in saliva/dentifrice slurries, the recognition of self‐assembled hexameric metallomacrocycles, ligand–protein exchange, the solubilizing effects of bile salts on an active pharmaceutical ingredient, the diffusion of cyclic peptides and studies on liquid electrolytes among many others.…”

Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids: Structural Analysis by Flow Field–Flow Fractionation/Multiangle Laser Light Scattering

“…In contrast, a distinct UV/VIS peak is clearly seen around 12-15 min though, with no detectable light scattering signal. This might be explained by the presence of pure cholate micelles (~2 nm diameter 13,31,32 ), which only scatter light to a very minor extent but exhibit a significant UV/VIS absorption at 205 nm. To further investigate, dispersions of sodium taurocholate, 3 and 6 mM, respectively, in phosphate buffer, were fractionated in the same manner as for FaSSIF-V1 (injection volume ¼ 50 mL corresponding to approximately 80.7 and 161.4 mg injected lipid mass, respectively) and one single UV/VIS peak was observed at the same retention time as seen in Figure 5 and there was no light scattering signal (data not shown).…”

“…Model studies have demonstrated that mixed micelles transit into phospholipid vesicles on dilution. 12 Vogtherr et al 13 reported the coexistence of both, mixed lecithinetaurocholate micelles and pure taurocholate micelles in FaSSIF, which, interestingly, displayed differences in solubilizing capacity/affinity toward the specific amphiphilic drug investigated. The aim of the present study thus was to establish an approach to separate different colloidal species present in intestinal fluids from each other according to their sizes in an analytical to small preparative manner.…”

“…Previous attempts to characterize the colloidal structures in artificial intestinal fluids (SIF) have been carried out using a combination of cryogenic transmission electron microscopy (Cryo-TEM) and photon correlation spectroscopy (PCS) 11,14 and recently with diffusion ordered spectroscopy (DOSY) NMR. 13 Kloefer et al applied Cryo-TEM imaging and reported rather monodisperse small colloids in FeSSIF, which were hypothesized to represent small mixed taurocholate/phospholipid micelles. For FaSSIF, they showed the copresence of 2 types of structures, likely mixed micelles and small vesicles/liposomes.…”