Construction of Drug–Polymer Thermodynamic Phase Diagrams Using Flory–Huggins Interaction Theory: Identifying the Relevance of Temperature and Drug Weight Fraction to Phase Separation within Solid Dispersions

Amorphous drug-polymer solid dispersions have the potential to enhance the dissolution performance and thus bioavailability of BCS class II drug compounds. The principle drawback of this approach is the limited physical stability of amorphous drug within the dispersion. Accurate determination of the solubility and miscibility of drug in the polymer matrix is the key to the successful design and development of such systems. In this paper, we propose a novel method, based on Flory-Huggins theory, to predict and compare the solubility and miscibility of drug in polymeric systems. The systems chosen for this study are (1) hydroxypropyl methylcellulose acetate succinate HF grade (HPMCAS-HF)-felodipine (FD) and (2) Soluplus (a graft copolymer of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol)-FD. Samples containing different drug compositions were mixed, ball milled, and then analyzed by differential scanning calorimetry (DSC). The value of the drug-polymer interaction parameter ? was calculated from the crystalline drug melting depression data and extrapolated to lower temperatures. The interaction parameter ? was also calculated at 25 °C for both systems using the van Krevelen solubility parameter method. The rank order of interaction parameters of the two systems obtained at this temperature was comparable. Diagrams of drug-polymer temperature-composition and free energy of mixing (?G mix) were constructed for both systems. The maximum crystalline drug solubility and amorphous drug miscibility may be predicted based on the phase diagrams. Hyper-DSC was used to assess the validity of constructed phase diagrams by annealing solid dispersions at specific drug loadings. Three different samples for each polymer were selected to represent different regions within the phase diagram

Essay - The role of ecological theory in microbial ecology

Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.

Atomic harmonic generation in time-dependent R-matrix theory

We have developed the capability to determine accurate harmonic spectra for multielectron atoms within time-dependent R-matrix (TDRM) theory. Harmonic spectra can be calculated using the expectation value of the dipole length, velocity, or acceleration operator. We assess the calculation of the harmonic spectrum from He irradiated by 390-nm laser light with intensities up to 4 x 10(14) W cm(-2) using each form, including the influence of the multielectron basis used in the TDRM code. The spectra are consistent between the different forms, although the dipole acceleration calculation breaks down at lower harmonics. The results obtained from TDRM theory are compared with results from the HELIUM code, finding good quantitative agreement between the methods. We find that bases which include pseudostates give the best comparison with the HELIUM code, but models comprising only physical orbitals also produce accurate results.

The electronic band structure of indium selenide:Photoemission and theory

The electronic band structure of vacuum cleaved single-crystal indium selenide has been investigated by X-ray and ultraviolet photoelectron spectroscopy. The valence band consists of three well separated groups, one derived from the Se 4s levels, and two derived from p-like wavefunctions. The band structure and valence band density of states has been calculated using a tight-binding single-layer approximation and all the major features in the experimental spectra are well accounted for. The spin-orbit splitting and electron loss structure associated with the In 4d core level is also reported.

Electronic properties of interfaces and defects from many-body perturbation theory: Recent developments and applications

We review some recent developments in many body perturbation theory (MBPT) calculations that have enabled the study of interfaces and defects. Starting from the theoretical basis of MBPT, Hedin's equations are presented, leading to the CW and CWI' approximations. We introduce the perturbative approach, that is the one most commonly used for obtaining quasiparticle (QP) energies. The practical strategy presented for dealing with the frequency dependence of the self energy operator is based on either plasmon-pole models (PPM) or the contour deformation technique, with the latter being more accurate. We also discuss the extrapolar method for reducing the number of unoccupied states which need to be included explicity in the calculations. The use of the PAW method in the framework of MBPT is also described. Finally, results which have been obtained using, MBPT for band offsets a interfaces and for defects presented, with companies on the main difficulties and cancels.

Schematic representation of the QP corrections (marked with ) to the band edges (E and E-v) and a defect level (F) for a Si/SiO2 interface (Si and O atoms are represented in blue and red, respectively, in the ball and stick model) with an oxygen vacancy leading to a Si-Si bond (the Si atoms involved in this bond are colored light blue).

Exchange-correlation energy and potential as approximate functionals of occupied and virtual Kohn-Sham orbitals: Application to dissociating H-2

The standard local density approximation and generalized gradient approximations fail to properly describe the dissociation of an electron pair bond, yielding large errors (on the order of 50 kcal/mol) at long bond distances. To remedy this failure, a self-consistent Kohn-Sham (KS) method is proposed with the exchange-correlation (xc) energy and potential depending on both occupied and virtual KS orbitals. The xc energy functional of Buijse and Baerends [Mol. Phys. 100, 401 (2002); Phys. Rev. Lett. 87, 133004 (2001)] is employed, which, based on an ansatz for the xc-hole amplitude, is able to reproduce the important dynamical and nondynamical effects of Coulomb correlation through the efficient use of virtual orbitals. Self-consistent calculations require the corresponding xc potential to be obtained, to which end the optimized effective potential (OEP) method is used within the common energy denominator approximation for the static orbital Green's function. The problem of the asymptotic divergence of the xc potential of the OEP when a finite number of virtual orbitals is used is addressed. The self-consistent calculations reproduce very well the entire H-2 potential curve, describing correctly the gradual buildup of strong left-right correlation in stretched H-2. (C) 2003 American Institute of Physics.

On the required shape corrections to the local density and generalized gradient approximations to the Kohn-Sham potentials for molecular response calculations of (hyper)polarizabilities and excitation energies

It is well known that shape corrections have to be applied to the local-density (LDA) and generalized gradient (GGA) approximations to the Kohn-Sham exchange-correlation potential in order to obtain reliable response properties in time dependent density functional theory calculations. Here we demonstrate that it is an oversimplified view that these shape corrections concern primarily the asymptotic part of the potential, and that they affect only Rydberg type transitions. The performance is assessed of two shape-corrected Kohn-Sham potentials, the gradient-regulated asymptotic connection procedure applied to the Becke-Perdew potential (BP-GRAC) and the statistical averaging of (model) orbital potentials (SAOP), versus LDA and GGA potentials, in molecular response calculations of the static average polarizability alpha, the Cauchy coefficient S-4, and the static average hyperpolarizability beta. The nature of the distortions of the LDA/GGA potentials is highlighted and it is shown that they introduce many spurious excited states at too low energy which may mix with valence excited states, resulting in wrong excited state compositions. They also lead to wrong oscillator strengths and thus to a wrong spectral structure of properties like the polarizability. LDA, Becke-Lee-Yang-Parr (BLYP), and Becke-Perdew (BP) characteristically underestimate contributions to alpha and S-4 from bound Rydberg-type states and overestimate those from the continuum. Cancellation of the errors in these contributions occasionally produces fortuitously good results. The distortions of the LDA, BLYP, and BP spectra are related to the deficiencies of the LDA/GGA potentials in both the bulk and outer molecular regions. In contrast, both SAOP and BP-GRAC potentials produce high quality polarizabilities for 21 molecules and also reliable Cauchy moments and hyperpolarizabilities for the selected molecules. The analysis for the N-2 molecule shows, that both SAOP and BP-GRAC yield reliable energies omega(i) and oscillator strengths f(i) of individual excitations, so that they reproduce well the spectral structure of alpha and S-4.(C) 2002 American Institute of Physics.

Exchange potential from the common energy denominator approximation for the Kohn-Sham Green's function: Application to (hyper)polarizabilities of molecular chains

An approximate Kohn-Sham (KS) exchange potential v(xsigma)(CEDA) is developed, based on the common energy denominator approximation (CEDA) for the static orbital Green's function, which preserves the essential structure of the density response function. v(xsigma)(CEDA) is an explicit functional of the occupied KS orbitals, which has the Slater v(Ssigma) and response v(respsigma)(CEDA) potentials as its components. The latter exhibits the characteristic step structure with "diagonal" contributions from the orbital densities \psi(isigma)\(2), as well as "off-diagonal" ones from the occupied-occupied orbital products psi(isigma)psi(j(not equal1)sigma). Comparison of the results of atomic and molecular ground-state CEDA calculations with those of the Krieger-Li-Iafrate (KLI), exact exchange (EXX), and Hartree-Fock (HF) methods show, that both KLI and CEDA potentials can be considered as very good analytical "closure approximations" to the exact KS exchange potential. The total CEDA and KLI energies nearly coincide with the EXX ones and the corresponding orbital energies epsilon(isigma) are rather close to each other for the light atoms and small molecules considered. The CEDA, KLI, EXX-epsilon(isigma) values provide the qualitatively correct order of ionizations and they give an estimate of VIPs comparable to that of the HF Koopmans' theorem. However, the additional off-diagonal orbital structure of v(xsigma)(CEDA) appears to be essential for the calculated response properties of molecular chains. KLI already considerably improves the calculated (hyper)polarizabilities of the prototype hydrogen chains H-n over local density approximation (LDA) and standard generalized gradient approximations (GGAs), while the CEDA results are definitely an improvement over the KLI ones. The reasons of this success are the specific orbital structures of the CEDA and KLI response potentials, which produce in an external field an ultranonlocal field-counteracting exchange potential. (C) 2002 American Institute of Physics.

Shape corrections to exchange-correlation potentials by gradient-regulated seamless connection of model potentials for inner and outer region

Shape corrections to the standard approximate Kohn-Sham exchange-correlation (xc) potentials are considered with the aim to improve the excitation energies (especially for higher excitations) calculated with time-dependent density functional perturbation theory. A scheme of gradient-regulated connection (GRAC) of inner to outer parts of a model potential is developed. Asymptotic corrections based either on the potential of Fermi and Amaldi or van Leeuwen and Baerends (LB) are seamlessly connected to the (shifted) xc potential of Becke and Perdew (BP) with the GRAC procedure, and are employed to calculate the vertical excitation energies of the prototype molecules N-2, CO, CH2O, C2H4, C5NH5, C6H6, Li-2, Na-2, K-2. The results are compared with those of the alternative interpolation scheme of Tozer and Handy as well as with the results of the potential obtained with the statistical averaging of (model) orbital potentials. Various asymptotically corrected potentials produce high quality excitation energies, which in quite a few cases approach the benchmark accuracy of 0.1 eV for the electronic spectra. Based on these results, the potential BP-GRAC-LB is proposed for molecular response calculations, which is a smooth potential and a genuine "local" density functional with an analytical representation. (C) 2001 American Institute of Physics.

From theory to practice:Improving the impact of health services research

Background: While significant strides have been made in health research, the incorporation of research evidence into healthcare decision-making has been marginal. The purpose of this paper is to provide an overview of how the utility of health services research can be improved through the use of theory. Integrating theory into health services research can improve research methodology and encourage stronger collaboration with decision-makers. Discussion: Recognizing the importance of theory calls for new expectations in the practice of health services research. These include: the formation of interdisciplinary research teams; broadening the training for those who will practice health services research; and supportive organizational conditions that promote collaboration between researchers and decision makers. Further, funding bodies can provide a significant role in guiding and supporting the use of theory in the practice of health services research. Summary: Institutions and researchers should incorporate the use of theory if health services research is to fulfill its potential for improving the delivery of health care. © 2005 Brazil et al; licensee BioMed Central Ltd.

Cognitive biases and addiction: an evolution in theory and method

An evolution in theoretical models and methodological paradigms for investigating cognitive biases in the addictions is discussed. Anomalies in traditional cognitive perspectives, and problems with the self-report methods which underpin them, are highlighted. An emergent body of cognitive research, contextualized within the principles and paradigms of cognitive neuropsychology rather than social learning theory, is presented which, it is argued, addresses these anomalies and problems. Evidence is presented that biases in the processing of addiction-related stimuli, and in the network of propositions which motivate addictive behaviours, occur at automatic, implicit and pre-conscious levels of awareness. It is suggested that methods which assess such implicit cognitive biases (e.g. Stroop, memory, priming and reaction-time paradigms) yield findings which have better predictive utility for ongoing behaviour than those biases determined by self-report methods of introspection. The potential utility of these findings for understanding "loss of control" phenomena, and the desynchrony between reported beliefs and intentions and ongoing addictive behaviours, is discussed. Applications to the practice of cognitive therapy are considered.

Deployment on GPUs of an application in computational atomic physics

This paper describes the deployment on GPUs of PROP, a program of the 2DRMP suite which models electron collisions with H-like atoms and ions. Because performance on GPUs is better in single precision than in double precision, the numerical stability of the PROP program in single precision has been studied. The numerical quality of PROP results computed in single precision and their impact on the next program of the 2DRMP suite has been analyzed. Successive versions of the PROP program on GPUs have been developed in order to improve its performance. Particular attention has been paid to the optimization of data transfers and of linear algebra operations. Performance obtained on several architectures (including NVIDIA Fermi) are presented.

Surface energy and surface proton order of the ice Ih basal and prism surfaces

Density-functional theory (DFT) is used to examine the basal and prism surfaces of ice Ih. Similar surface energies are obtained for the two surfaces; however, in each case a strong dependence of the surface energy on surface proton order is identified. This dependence, which can be as much as 50% of the absolute surface energy, is significantly larger than the bulk dependence (< 1%) on proton order, suggesting that the thermodynamic ground state of the ice surface will remain proton ordered well above the bulk order-disorder temperature of about 72 K. On the basal surface this suggestion is supported by Monte Carlo simulations with an empirical potential and solution of a 2D Ising model with nearest neighbor interactions taken from DFT. Order parameters that define the surface energy of each surface in terms of nearest neighbor interactions between dangling OH bonds (those which point out of the surface into vacuum) have been identified and are discussed. Overall, these results suggest that proton order-disorder effects have a profound impact on the stability of ice surfaces and will most likely have an effect on ice surface reactivity as well as ice crystal growth and morphology. S Supplementary data are available from stacks.iop.org/JPhysCM/22/074209/mmedia

Susceptibility to environmentally induced cracking of laser-welded NiTi wires in Hanks’ solution at open-circuit potential

In the present study the tensile and super-elastic behaviours of laser-welded NiTi wires in Hanks’ solution at open-circuit potential (OCP) were investigated using tensile and cyclic slow-strain-rate tests (SSRT). In comparison with NiTi weldment tested in oil (non-corrosive environment), the weldment in Hanks’ solution suffered from obvious degradation in the tensile properties as evidenced by lower tensile strength, reduced maximum elongation, and a brittle fracture mode. Moreover, a larger residual strain was observed in the weldment after stress–strain cycles in Hanks’ solution. In addition to the microstructural defects resulting from the welding process, the inferior tensile and super-elastic behaviours of the NiTi weldment in Hanks’ solution could be attributed to the trapping of a large amount of hydrogen in the weld zone and heat-affected zone.

Anisotropy parameters in two-color two-photon above-threshold ionization

We employ the time-dependent R-matrix (TDRM) method to calculate anisotropy parameters for positive and negative sidebands of selected harmonics generated by two-color two-photon above-threshold ionization of argon. We consider odd harmonics of an 800-nm field ranging from the 13th to 19th harmonic, overlapped by a fundamental 800-nm IR field. The anisotropy parameters obtained using the TDRM method are compared with those obtained using a second-order perturbation theory with a model potential approach and a soft photon approximation approach. Where available, a comparison is also made to published experimental results. All three theoretical approaches provide similar values for anisotropy parameters. The TDRM approach obtains values that are closest to published experimental values. At high photon energies, the differences between each of the theoretical methods become less significant.