2,581 research outputs found
Impact of Endogenous Bile Salts on the Thermodynamics of Supersaturated Active Pharmaceutical Ingredient Solutions
A variety of formulation strategies have been developed to mitigate the inadequate aqueous solubility of certain therapeutic agents. Among these, achieving supersaturation in vivo is a promising approach to improve the extent of oral absorption. Because of the thermodynamic instability of supersaturated solutions, inhibitors are needed to kinetically hinder crystallization. In addition to commonly used polymeric additives, bile salts, naturally present in the gastrointestinal tract, have been shown to exhibit crystallization inhibition properties. However, the impact of bile salts on solution thermodynamics is not well understood, although this knowledge is essential in order to explore the mechanism of crystallization inhibition. To better describe solution thermodynamics in the presence of bile salts, a side-by-side diffusion cell was used to evaluate solute flux for solutions of telaprevir in the absence and presence of the six most abundant bile salts in human intestinal fluid at various solute concentrations; flux measurements provide information about the solute thermodynamic activity and hence can provide an improved measurement of supersaturation in complex solutions. Trihydroxy bile salts had minimal impact on solution phase boundaries as well as solute flux, while micellar dihydroxy bile salts solubilized telaprevir leading to reduced solute flux across the membrane. An inconsistency between the concentration-based supersaturation ratio and that based on solute thermodynamic activity (the fundamental driving force for crystallization) was noted, suggesting that the activity-based supersaturation should be determined to better interpret any modification in crystallization kinetics in the presence of these additives. These findings indicate that bile salts are not interchangeable from a thermodynamic perspective and provide a foundation for further studies evaluating the mechanism of crystallization inhibition
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Suppression of Zeeman Relaxation in Cold Collisions of Atoms
We present a combined experimental and theoretical study of angular momentum depolarization in cold collisions of atoms in the presence of an external magnetic field. We show that collision-induced Zeeman relaxation of Ga and In atoms in cold He gas is dramatically suppressed compared to atoms in states. Using rigorous quantum-scattering calculations based on ab initio interaction potentials, we demonstrate that Zeeman transitions in collisions of atoms in electronic states occur via couplings to the state induced by the anisotropy of the interaction potential. Our results suggest the feasibility of sympatheticthetic cooling and magnetic trapping of -state atoms, such as halogens, thereby opening up exciting areas of research in precision spectroscopy and cold-controlled chemistry.Physic
Modelling the transport of oil after a proposed oil spill accident in Barents Sea and its environmental impact on Alke species
OA Green publisher. Can archive pre-print and post-print or publisher's version/PDF.
Link to publisher's version: http://doi.org/10.1088/1755-1315/82/1/012010Accidental oil spills can have significant effect on the coastal and marine environment. As the oil extraction and exploration activities increase in the Barents Sea, it is of increasingly importance to investigate the potential oil spill incidents associated with these activities. In this study, the transport and fate of oil after a proposed oil spill incident in Barents Sea was modelled by oil spill contingency and response model OSCAR. The possibility that the spilled oil reach the open sea and the strand area was calculated respectively. The influence area of the incident was calculated by combining the results from 200 simulations. The possibility that the spilled oil reach Alke species, a vulnerable species and on the National Red List of birds in Barents Sea, was analyzed by combining oil spill modelling results and the Alke species distribution data. The results showed that oil is dominated with a probability of 70-100% in the open sea to reach an area in a radius of 20km from the release location after 14 days of release. The probability reduces with the increasing distances from the release location. It is higher possibility that the spilled oil will reach the Alke species in the strand area than in the open sea in the summer. The total influence area of the release is 11 429 km2 for the surface water and 1528 km2 for the coastal area
Integral equation method for the electromagnetic wave propagation in stratified anisotropic dielectric-magnetic materials
We investigate the propagation of electromagnetic waves in stratified
anisotropic dielectric-magnetic materials using the integral equation method
(IEM). Based on the superposition principle, we use Hertz vector formulations
of radiated fields to study the interaction of wave with matter. We derive in a
new way the dispersion relation, Snell's law and reflection/transmission
coefficients by self-consistent analyses. Moreover, we find two new forms of
the generalized extinction theorem. Applying the IEM, we investigate the wave
propagation through a slab and disclose the underlying physics which are
further verified by numerical simulations. The results lead to a unified
framework of the IEM for the propagation of wave incident either from a medium
or vacuum in stratified dielectric-magnetic materials.Comment: 14pages, 3figure
Maintaining Supersaturation of Active Pharmaceutical Ingredient Solutions with Biologically Relevant Bile Salts
Currently, it is of interest to improve the oral absorption of poorly water-soluble therapeutic agents using supersaturating formulations. Understanding crystallization kinetics of supersaturated drug solutions is central to the design and evaluation of such formulations. Bile salts have drawn increasing attention in this context as they serve important roles in biorelevant dissolution media, in vivo, and have been shown to slow down the crystallization of active pharmaceutical ingredients. The goal of this study was to evaluate the impact of bile salt monomers and micelles on the crystallization of telaprevir, a poorly water-soluble drug, from aqueous solution. To better describe the crystallization driving force in the presence of the bile salts, a side-by-side diffusion cell was used to evaluate telaprevir mass flow rate, and hence solute activity, in the absence and presence of different bile salts. The effectiveness of monomeric and miceller bile salts as crystallization inhibitors was then evaluated by performing crystallization induction time experiments at constant, activity-based supersaturation. The six most abundant biologically relevant bile salts were investigated (sodium taurocholate, sodium taurodeoxycholate, sodium taurochenodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium glycochenodeoxycholate). All six bile salts exhibited nucleation inhibition properties in both homogeneous supersaturated telaprevir solutions and highly supersaturated telaprevir solutions containing a second phase. The ability to retard telaprevir nucleation, however, varied among the bile salts and also depended on the aggregation state. Monomeric bile salts were found to be effective crystallization inhibitors. At higher bile salt concentrations, trihydroxy bile salts showed better inhibition compared to dihydroxy bile salts. These results highlight the importance of considering the composition of the test medium used to evaluate product performance, in particular in the context of evaluating crystallization kinetics
Supergravity Solutions for Harmonic, Static and Flux S-Branes
We seek S-brane solutions in D=11 supergravity which can be characterized by
a harmonic function H on the flat transverse space. It turns out that the
Einstein's equations force H to be a linear function of the transverse
coordinates. The codimension one H=0 hyperplane can be spacelike, timelike or
null and the spacelike case reduces to the previously obtained SM2 or SM5 brane
solutions. We then consider static S-brane configurations having smeared
timelike directions where the transverse Lorentzian symmetry group is broken
down to its maximal orthogonal subgroup. Assuming that the metric functions
depend on a radial spatial coordinate, we construct explicit solutions in D=11
supergravity which are non-supersymmetric and asymptotically flat. Finally, we
obtain spacelike fluxbrane backgrounds which have timelike electric or magnetic
fluxlines extending from past to future infinity.Comment: 22 pages, v2: references adde
Localized Intersections of Non-Extremal p-branes and S-branes
A class of solutions to Supergravity in 10 or 11 dimensions is presented
which extends the non-standard or semi-local intersections of Dp-branes to the
case of non-extremal p-branes. The type of non-extremal solutions involved in
the intersection is free and we provide two examples involving black-branes
and/or D-\bar{D} systems. After a rotation among the time coordinate and a
relatively transverse radial direction the solutions admit the interpretation
of an intersection among D-branes and S-branes. We speculate on the relevance
of these configurations both to study time dependent phenomena in the AdS/CFT
correspondence as well as to construct cosmological brane-world scenarios
within String Theory admitting accelerating expansion of the Universe.Comment: 31 pages, latex file; v2: typos corrected and references adde
Correlation and disorder-enhanced nematic spin response in superconductors with weakly broken rotational symmetry
Recent experimental and theoretical studies have highlighted the possible
role of a electronic nematic liquid in underdoped cuprate superconductors. We
calculate, within a model of d-wave superconductor with Hubbard correlations,
the spin susceptibility in the case of a small explicitly broken rotational
symmetry of the underlying lattice. We then exhibit how the induced spin
response asymmetry is strongly enhanced by correlations as one approaches the
instability to stripe order. In the disorder-induced stripe phase, impurities
become spin nematogens with a C_2 symmetric impurity resonance state, and the
disorder-averaged spin susceptibility remains only C_2 symmetric at low
energies, similar to recent data from neutron scattering experiments on
underdoped YBCO.Comment: 6 pages, 5 figure
Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient
Bile salts are endogenous surfactants present in the human gastrointestinal tract in the form of mixed micelles that also contain phospholipids. Due to the inevitable encounter of oral drug formulations with bile salts, it is important to understand the impact of bile salts on the crystallization tendency of poorly soluble compounds that form supersaturated solutions in vivo in order to maximize oral drug absorption. Although there has been an increasing number of studies focusing on the role of individual bile salts on drug crystallization, the effects of mixed micelles and biorelevant media composition on crystallization kinetics have only been studied to a limited extent. In this study, we evaluated the ability of binary and ternary bile salt combinations to maintain supersaturated aqueous solutions of telaprevir. Crystallization kinetics were also compared in more complex media that also contained the phospholipid, lecithin. These included fasted state simulated intestinal fluid (FaSSIF) (a widely used medium for formulation testing which contains a single bile salt, sodium taurocholate), and media that contained several endogenous bile salts. Finally, the combined effects of a polymer, hydroxypropyl methyl cellulose acetate succinate, and the testing media on crystallization kinetics were evaluated to provide insights into supersaturation formulation design. Solution bile salt composition was found to significantly influence crystallization kinetics. However, the presence of the polymer increased induction times sufficiently that differences between media were minimized. This study suggests that when evaluating the crystallization kinetics of systems with a propensity to undergo supersaturation in vivo, attention should be paid to selecting biorelevant media
Resonance Effects in the Nonadiabatic Nonlinear Quantum Dimer
The quantum nonlinear dimer consisting of an electron shuttling between the
two sites and in weak interaction with vibrations, is studied numerically under
the application of a DC electric field. A field-induced resonance phenomenon
between the vibrations and the electronic oscillations is found to influence
the electronic transport greatly. For initially delocalization of the electron,
the resonance has the effect of a dramatic increase in the transport. Nonlinear
frequency mixing is identified as the main mechanism that influences transport.
A characterization of the frequency spectrum is also presented.Comment: 7 pages, 6 figure
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