Water deuteron NMR spectra have been studied for the system dipalmitoyllecithin (DPL)-heavy water (D2O) at different compositions and temperatures. From an analysis of the spectra in terms of quadrupole splittings, a phase diagram has been constructed for the temperature range 25-60 degrees C and the composition range 4-15 mol of D2O/mol of DPL. Evidence is given that the "pretransition" observed by differential scanning calorimetry is caused by a crossing of a three-phase line. Strong support for a specific hydration of about 11 water molecules per lecithin molecule in the phase between the pretransition and main transition is also found.
The molecular organization in the hexagonal and lamellar phases of the ternary systems lecithin--sodium cholate--water has been investigated by using a variety of nuclear magnetic resonance techniques. The main findings and conclusions are the following: (i) When calculated on a mole fraction basis, the phase equilibria are insensitive to changes in the alkyl chains of the lecithin. (ii) When incorporated into a lecithin bilayer, cholate exerts a strong perturbation on the lecithin alkyl chain order, giving a large decrease of the order parameters. (iii) This decrease of the order occurs since the average cross-sectional area per alkyl chain increases probably as a result of cholate placing itself flat on the bilayer surface. (iv) The diffusion of lecithin molecules is approximately equally rapid in the lamellar and hexagonal phases. (v) The hexagonal phase is formed by rodlike aggregates with the polar groups at the surface of the rods and with a continuous hydrocarbon core. The rods are not formed by stacking disklike mixed micelles. (vi) With the interpretations of the molecular packing and the phase structures, the observed phase equilibria are in good agreement with current theories of the factors that govern phase behavior in amphiphile--water systems.
SUMMARYAims: To investigate the gastrointestinal pharmacokinetics of controlled-release (Entocort) and standard budesonide capsules. Methods: Six Crohn's disease patients and eight healthy controls were given controlled-release capsules containing budesonide and an inert 111 In label, following breakfast. In the patients, a standard capsule containing deuterium-labelled budesonide was given simultaneously. In the controls, on a separate occasion, the controlled-release capsules were given in the fasting state. Gastrointestinal transit was recorded by a gamma camera. Plasma budesonide and deuterium-labelled budesonide were used to estimate drug release, and urine cortisol was used to assess systemic effects.Results: Budesonide delivery to the ileo-colonic region was significantly greater after the intake of the controlled-release capsules [69%; 95% confidence interval (CI), 54-84] than after the standard capsules (30%; 95% CI, 15-45) (P ¼ 0.005). Fasting had little impact on uptake. The transit and pharmacokinetics of budesonide were similar in both subject groups, although systemic availability was higher in patients (21%; 95% CI, 13-33) than in controls (12%; 95% CI, 10-14) (P ¼ 0.009). Urinary cortisol was, however, similar in both groups. Conclusions: A major fraction of budesonide is released in the ileum and throughout the colon, the intended target for the controlled-release formulation. The prandial state has little effect on budesonide uptake.
Publicatlon costs assisted by the University of LundThe properties of viscoelastic dilute aqueous solutions containing the hexadecyltrimethylammonium cation (CTA+) are investigated by monitoring the proton magnetic resonance spectrum and the linear dichroism induced in a shear gradient. It is found that the viscoelastic behavior of the dilute solutions correlates with the formation of rod-shaped micellar aggregates. This correlation is manifested both with respect to changes in composition and in temperature. It is suggested that the behavior of the solutions is caused by the presence of a periodic colloidal structure formed due to the repulsive force between the aggregates.
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