Terms Of Free Volume Research Articles

COSMOPharm: Drug-Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC.

The quantum mechanics-aided COSMO-SAC activity coefficient model is applied and systematically examined for predicting the thermodynamic compatibility of drugs and polymers. The drug-polymer compatibility is a key aspect in the rational selection of optimal polymeric carriers for pharmaceutical amorphous solid dispersions (ASD) that enhance drug bioavailability. The drug-polymer compatibility is evaluated in terms of both solubility and miscibility, calculated using standard thermodynamic equilibrium relations based on the activity coefficients predicted by COSMO-SAC. As inherent to COSMO-SAC, our approach relies only on quantum-mechanically derived σ-profiles of the considered molecular species and involves no parameter fitting to experimental data. All σ-profiles used were determined in this work, with those of the polymers being derived from their shorter oligomers by replicating the properties of their central monomer unit(s). Quantitatively, COSMO-SAC achieved an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data. Qualitatively, COSMO-SAC correctly categorized different polymer types in terms of their compatibility with drugs and provided meaningful estimations of the amorphous-amorphous phase separation. Furthermore, we analyzed the sensitivity of the COSMO-SAC results for ASD to different model configurations and σ-profiles of polymers. In general, while the free volume and dispersion terms exerted a limited effect on predictions, the structures of oligomers used to produce σ-profiles of polymers appeared to be more important, especially in the case of strongly interacting polymers. Explanations for these observations are provided. COSMO-SAC proved to be an efficient method for compatibility prediction and polymer screening in ASD, particularly in terms of its performance-cost ratio, as it relies only on first-principles calculations for the considered molecular species. The open-source nature of both COSMO-SAC and the Python-based tool COSMOPharm, developed in this work for predicting the API-polymer thermodynamic compatibility, invites interested readers to explore and utilize this method for further research or assistance in the design of pharmaceutical formulations.

The Effect of a Coating on the Crystallization of Multicomponent Co-Based Amorphous Alloys

The effect of protective coatings on the crystallization of amorphous Co-based alloys was studied using the methods of X-ray diffraction, differential scanning calorimetry, and transmission electron microscopy. The crystallization of the amorphous alloys was studied on as-prepared samples, deformed samples, and deformed samples with a protective coating. After heat treatment, the fraction of the crystalline phase in the pre-deformed samples was higher than in the undeformed samples. When using a protective coating, the fraction of nanocrystals formed during heat treatment increased. The size of the crystals formed in deformed samples was smaller, and in the deformed samples with a protective coating, they were slightly larger than in the corresponding initial samples. The reasons for the differences in the formed structure in the amorphous alloys under study are discussed in terms of free volume.

In Search of a Molecular View of Peptide-Lipid Interactions in Membranes.

Lipid bilayer membranes are often represented as a continuous nonpolar slab with a certain thickness bounded by two more polar interfaces. Phenomena such as peptide binding to the membrane surface, folding, insertion, translocation, and diffusion are typically interpreted on the basis of this view. In this Perspective, I argue that this membrane representation as a hydrophobic continuum solvent is not adequate to understand peptide-lipid interactions. Lipids are not small compared to membrane-active peptides: their sizes are similar. Therefore, peptide diffusion needs to be understood in terms of free volume, not classical continuum mechanics; peptide solubility or partitioning in membranes cannot be interpreted in terms of hydrophobic mismatch between membrane thickness and peptide length; peptide folding and translocation, often involving cationic peptides, can only be understood if realizing that lipids adapt to the presence of peptides and the membrane may undergo considerable lipid redistribution in the process. In all of those instances, the detailed molecular interactions between the peptide residues and the lipid components are essential to understand the mechanisms involved.

The roles of polymer relaxation phenomena, aqueous dye solubility and the physical properties of water in the mechanism of adsorption of a disperse dye on poly(ethylene terephthalate) fibres: Part 2 dye solubility

AbstractThe marked temperature‐dependent uptake of a commercial disperse dye on poly(ethylene terephthalate) fabric achieved during an aqueous high temperature dyeing process is the likely amalgamation of at least two separate, but intrinsically inter‐related, thermally activated processes, namely, poly(ethylene terephthalate) structural relaxations, as articulated in terms of polymer chain segmental mobility and available free volume, in which glass transition adopts a principal role, as well as disperse dye aqueous solubility. Both polymer relaxation times and disperse dye solubility therefore assume crucially important roles in the mechanism of adsorption of disperse dyes on poly(ethylene terephthalate) fibres.

Explaining the Sensitivity of Polymer Segmental Relaxation to Additive Size Based on the Localization Model.

We use molecular simulations to examine how the dynamics of a coarse-grained polymer melt are altered by additives of variable size and interaction strength with the polymer matrix. The effect of diluent size σ on polymer dynamics changes significantly when its size is comparable to the polymer segment size. For each σ, we show that the localization model (LM) quantitatively describes the dependence of the segmental relaxation time τ on temperature T in terms of dynamic free volume, quantified by the Debye-Waller factor ⟨u^{2}⟩. Within this model, we show that the additive size alone controls the functional form of the T dependence. The LM parameters reach asymptotic values when the diluent size exceeds the monomer size, converging to a limit applicable to macroscopic interfaces.

Atomic-level characterization of free volume in the structure of Cu67Zr33 amorphous alloy

The structure of Cu67Zr33 amorphous alloy was investigated in terms of packing density and free volume by using neutron, x-ray diffraction and reverse Monte Carlo (RMC) modelling. The RMC model was analysed by a method of decomposing the three-dimensional atomic configuration into fundamental polyhedral units (termed as ‘holes’ referencing the Bernal’s works) of which faces are all triangles consisting of chemical bonds. Not only tetrahedral and octahedral holes but also other larger holes were identified. Moreover, the atomic packing fractions and free volumes in the respective polyhedral holes were evaluated with reference to those for the corresponding crystal structures. The results show that the distribution of free volumes for the larger holes can be described by the exponential function assuming that there are no energetic interactions between each other. On the other hand, the local structural fluctuations due to densely and loosely packed tetrahedral holes were observed, leading to the negative free volume spaces.

Binary mixtures of 2-methyl cyclohexanone with various functional groups (Thermodynamic and acoustic properties)

In the binary mixtures of 2-methylcyclohexanone with various functional groups (3-methyl aniline, 4-methoxy benzyl alcohol, 4-hydroxy benzoic acid and isobutyric acid) the densities, and speeds of sound including those of pure liquids, were measured over the entire composition range at different temperatures (303.15, 308.15 and 313.15) K and atmospheric pressure 0.1 MPa. Using these experimentally determined data, the excess values of molar volume, isentropic compressibility of the studied binary mixtures and partial molar volumes, partial molar isentropic compressibilities of these pure components at infinite dilution were calculated. The results are discussed both in terms of free volume and proton donor–acceptor interactions between the unlike molecules.

Estimated funding assessment for hospitals functioning as enterprise

The purpose of the article is to identify the possibilities of medical institutions development in the conditions of change of health care financing mechanism with taking into account the further orientation on autonomization of medical institutions, which received the status of enterprises.The paper implies active implementation of new planning methods that are alternative to the traditional national approach to expenses accounting and their analysis, which are fundamentals of planned fi- nancial indicators calculation.The transformation of the financial mechanism in the healthcare sector necessitates a financial provision for medical institutions, that includes, first and foremost, a reasonable calculation of cost of medical in- stitutions services.Methodology.The methodology of the study is to use a combina- tion of methods: economic analysis, synthesis, comparison – to estimate the ac- tual values of financial indicators; economic-mathematical modeling and forecast- ing; systematic analysis, typification and comparison of observations, grouping, generalizations – during the process of making final conclusions based on the results of analytical studies.The scientific noveltyof the resultsobtainedconsistsnew approach offered by authors that let medical institutionsolve existing practical and methodological issues of correlation between current actual expenses and, forecast financial needs of medical institution in variable functioning conditions. The au- thors prove that the further development of medical institutions is impossible without reasonable pricing of healthcare services. The existing «Methodology of healthcare services cost calculation»is aimed at standardization and unification of expenses accounting methods, but does not promote getting veracious calculable data, which should be used in financial planning and modelling. Conclusions.The combination of analysis methods presented in this paper enables to make a forecast about the financial needs of the medical institution in the status of the enterprise on the basis of scientifically-based approaches. The use of the CVP-analysis meth- od allows to purposefully manage the main financial indicators that are taken into account in different scenarios, and the correctness of their analytical application at the hospital level is included in a justified approach to a higher level of gener- alization in accordance with the theory of averages.There is a high bankruptcy risk for a medical institution in the status of an enterprise in a case of insufficient level of reimbursement of medical institution expenses within the limits of state medical insurance, as well as within limited possibilities of receiving income from paid medical services. For more effective realization of medical institutions «au- tonomization», it is necessary to improve the legislation in terms of free choice of the list and volume of paid medical services, economic approaches to pricing for paid medical services and a clear policy of the state within a support of health care capital investment programs.Effective, purposeful preparatory work of reason- able financial indicators usage, taking into account current legislation, will enable the medical institutions to be competitive in the healthcare market.

Explaining the T,V-dependent dynamics of glass forming liquids: The cooperative free volume model tested against new simulation results.

In this article, we derive a rate model, the "cooperative free volume" (CFV) model, to explain relaxation dynamics in terms of a system's free volume, Vfree, and its temperature, T, over widely varied pressure dependent conditions. In the CFV model, the rate a molecule moves a distance on the order of its own size is dependent on the cooperation of surrounding molecules to open up enough free space. To test CFV, we have generated extensive T,V dependent simulation data for structural relaxation times, τ, on a Kob and Andersen type Lennard-Jones (KA-LJ) fluid. The Vfree = V - Vhc values are obtained by estimating the limiting hard core volume, Vhc, through analysis of the KA-LJ PVT data. We provide the first simulation evidence that shows ln τ to be linearly proportional to 1/Vfree on isotherms, with T-dependent slopes, thus confirming our recent analysis of experimental systems. The linear relationship exhibited by the simulation data is further shown to occur at temperatures both above and below the transition to Arrhenius behavior. We also show that the gas kinetic T-dependent contribution is important in simulation results and that there can be a significant entropic contribution from lingering molecular hard-cores at high T. A key result is that non-Arrhenius relaxation behavior is always exhibited on isobars of the KA-LJ fluid, even at high T. The CFV model predicts all of this behavior over a surprisingly wide range of the KA-LJ T,V space, fitting it with just a single set of three parameters. The CFV approach leads to a framework wherein the number of cooperating particles, and thus, the process free energy of activation, is inversely proportional to Vfree, and this is the foundation for the form of the model's volume contribution, a form that we find to hold for all systems and at all temperatures.

Properties of aqueous solutions of ammonium-based ionic liquids and thermodynamic modelling using Flory theory

The new protic ionic liquids mixtures properties and water are of great interest from a theoretical perspective. The objective of this study is to establish mixtures with different densities, viscosities, composition ranges and temperatures. The studied ionic liquids are N-methyl-2-hydroxy-ethylammonium acetate (m-2HEAA), N-methyl-2-hydroxy-ethylammonium propionate (m-2HEAPr) and N-methyl-2-hydroxy-ethylammonium butanoate (m-2HEAB), all based on the N-methyl-2-hydroxy-ethylammonium cation. The excess volume data are correlated using the Prigogine-Flory-Patterson equation of state (EOS) to evaluate the importance of their contributions with respect to the studied mixtures. The viscosity data were modeled combining Eyring mixture law for viscosity and excess Gibbs energy from Flory-Huggins model. The results reveal a large range of negative deviation and a non-significant contribution of the free EOS volume term compared to the interactional contribution and characteristic pressure terms. In general, the models studied in this work presented good agreement with the experimental data.

Guide to Asphaltene Solubility

A guide to the solubility of asphaltenes in a range of solvents is constructed through the use of an association model to account for asphaltene nanoaggregation and its effect on phase behavior and Hildebrand solubility parameters to model interactions between aggregates and solvent. Solvents are classified according to their polarity and ability to self-associate (e.g., through hydrogen bonds). In addition, estimates of the contribution of free volume terms to interaction parameters indicate that a further distinction must be made between solvents with flexible molecules (such as the n-paraffins) and those that are relatively inflexible (such as toluene). A “bare” interaction parameter (χ0) is calculated, and it is this parameter that is related to Hildebrand solubility parameters. For nonpolar and weakly polar solvents, a critical value of the solubility parameter difference (Δδc) between an asphaltene or asphaltene component and solvent is calculated to be ±3.5 MPa0.5 at 25 °C for a nonpolar or weakly polar solvents with largely inflexible molecules and a molar volume of 100 cm3/mol. For flexible solvents such as the n-paraffins, free volume effects are larger and Δδc is about ±2.8 MPa0.5. For strongly polar solvents that have limited flexibility, the equivalent critical value of the solubility parameter difference is also calculated to be ±2.8 MPa0.5. Hydrogen bonded solvents like methanol are calculated to be immiscible with asphaltenes, with miscibility being defined as forming a single phase across the composition range (at 25 °C). Miscibility maps are constructed in terms of the calculated phase boundary at the critical point, δA ± Δδc, where δA is the asphaltene component solubility parameter, plotted as a function of solvent molar volume. The solubility of asphaltenes and asphaltene components in various solvents is discussed. The solvent that defines asphaltene identity, toluene, is predicted to dissolve only a limited range of asphaltene components. This is consistent with various reported experimental observations. However, solubility is often defined in terms of an absence of a visible precipitate, and on the basis of recent work in the literature, toluene solutions may contain some microphase-separated material stabilized against further aggregation by steric and kinetic factors.

Gas permeation properties of poly(sulfone-co-ethylene glycol) membranes containing bis(phenyl)fluorene moieties

Copolymers based on glassy and rubbery units have been developed to take advantages of both domains to enhance solubility and diffusivity. Well-tuned microstructure in copolymers has provided high gas permeability and selectivity. In this study, we report on the syntheses and characterizations of copolymers using poly(ethylene glycol) and high free volume polysulfone. Bulky and flexible bis(phenyl)fluorene moiety is introduced in polysulfone domain. Comparison between conventional bisphenol-A based polysulfone and the polysulfone in this work is made in terms of fractional free volume and gas permeation properties. In the poly(sulfone-co-ethylene glycol), the composition of sulfone/ethylene glycol results in the improvement of thermal and physical properties. Copolymers are characterized using gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, wide angle X-ray diffraction, and gas permeation measurements.

The Effect of the Molecular Size and Shape on the Volume Behavior of Binary Liquid Mixtures. Branched and Cyclic Alkanes in Heptane at 298.15 K

Excess molar volumes VE for 40 mixtures of heptane with a liquid alkane and apparent molar volumes in heptane for eight solid alkanes have been obtained at 298.15 K. They include five linear, 30 branched-chain, and 13 cyclic alkanes. Almost all systems exhibit negative VE values. For mixtures with open chain alkanes, VE increases from C5 to C7 and then decreases. A similar trend is shown by mixtures with cycloalkanes. VE values are compared with known HE data for mixtures with heptane and tetrachloromethane. Signs and trends of VE and HE are correlated with the free volume and interactional terms of the Flory theory. The partial molar volumes at infinite dilution in heptane, V°, have also been obtained and discussed together with literature data on other hydrocarbons and polar compounds. The calculated contributions to V° by CH3, CH2, CH and C groups are compared with previously determined contributions of polar groups. The lower contributions of the latter groups are explained with the volume contraction caused by dipole-induced dipole interaction. The volume effects associated with branching and cyclization have been evaluated and compared with the corresponding effects on solvation enthalpy. The branching effect, in the order of magnitude of few cm3·mol−1, and the larger negative values of cyclization volumes, down to −24 cm3·mol−1, are discussed in terms of packing and solute–solvent interactions, in analogy to polar organic solutes either in heptane and tetrachloromethane. A negative cyclization effect is also exhibited by the solvation enthalpies.

Permeability of Fluid-Phase Phospholipid Bilayers: Assessment and Useful Correlations for Permeability Screening and Other Applications

Permeability data (P(lip/w) ) for liquid crystalline phospholipid bilayers composed of egg lecithin and dimyristoylphosphatidylcholine (DMPC) are analyzed in terms of a mathematical model that accounts for free surface area and chain-ordering effects in the bilayer as well as size and lipophilicity of the permeating species. Free surface area and chain ordering are largely determined by temperature and cholesterol content of the membrane, molecular size is represented by molecular weight, and lipophilicity of the barrier region is represented by the 1,9-decadiene/water partition coefficient, following earlier work by Xiang, Anderson, and coworkers. A correlating variable χ = MW(n) σ/(1 -σ) is used to link the results from different membrane systems, where different values of n are tried, and σ denotes a reduced phospholipid density. The group (1 -σ)/σ is a measure of free surface area, but can also be interpreted in terms of free volume. A single exponential function of χ is developed that is able to correlate 39 observations of P(lip/w) for different compounds in egg lecithin at low density, and 22 observations for acetic acid in DMPC at higher densities, spanning nine orders of magnitude to within an rms error for log 10 P(lip/w) of 0.20. The best fit found for n = 0.87 ultimately makes χ much closer to the ratio of molecular to free volumes than surface areas. The results serve as a starting point for estimating passive permeability of cell membranes to nonionized solutes as a function of temperature and cholesterol content of the membrane.

Loading rate sensitivity of nanoindentation creep behavior in a Fe-based bulk metallic glass

Effect of loading rate on room temperature creep deformation of {[(Fe0.6Co0.4)0.75B0.2Si0.05]0.96Nb0.04}96Cr4 bulk metallic glass (BMG) was investigated by performing nanoindentation creep experiments. Experimental results show that the creep displacement of the Fe-based BMG increases with increasing the loading rate. Furthermore, based on an empirical power-law equation, the stress exponent for room temperature creep of this BMG was calculated. As the indentation loading rate increases from 1 mN/s to 50 mN/s, the stress exponent decreases gradually from 28.1 down to 4.9, exhibiting significant indentation loading rate sensitivity. Finally, nanoindentation creep behavior in this Fe-based BMG was demonstrated in terms of free volume and “shear transformation zone” (STZ) theories, which could provide semi-quantitative explanation as for the observed experimental and analytical results.

Correlation of soft magnetic properties with free volume and medium range ordering in metallic glasses probed by fluctuation microscopy and positron annihilation technique

Amorphous ribbons of different thicknesses of Co64.5Fe3.5Si16B14Ni2 alloy were synthesized using the melt spinning technique by varying wheel speed. The effect of cooling rate on the ribbon thickness and their soft magnetic properties have been studied. The amorphous structure has been characterized in terms of structural free volume and medium range order (MRO) by positron annihilation spectroscopy and fluctuation electron microscopy techniques. Positron lifetime spectra of amorphous samples showed two lifetime components. The first component was found to be correlated with MRO whereas, the second lifetime component was found to be associated with nanovoid type of defects, and the second component was strongly dependent on processing conditions. It could be established that the coercivity of the amorphous samples produced by the rapid solidification technique mainly depends on the defects formed during processing rather than change induced in MRO.

An effective tool to characterize adhesion at the interface of binary polymer blends: a free volume study

Abstract In this work, an effective method of characterizing the adhesion at the interface of partially miscible and immiscible binary polymer is used. Three polymer blends namely PS/PMMA, PP/NBR and PVC/SAN were irradiated with e-beam and microwaves, in order to bring about interfacial modification, and were characterized in terms of free volume measured by Positron Lifetime technique. The changes in free volume parameters upon e-beam and microwave irradiation on the two systems clearly shows improved interaction between the blend constituents as a result of cross-linking through hydrogen bond formation. However, the extent of interfacial modification brought in at different weight compositions is not forthcoming. Therefore, the hydrodynamic interaction parameter α, which accounts for friction at the interface between the dissimilar chains of the blend constituents, is evaluated from the very same free volume data. Since α represents the strength of hydrodynamic interaction, it could be taken as an indicator of the adhesion strength at the interface. Present results showed that both e-beam and microwave irradiations can be used to stabilize the interfaces in binary polymer blends as evidenced by hydrodynamic interaction.

Prediction of Bulk Density and Molecular Packing in Model Dendrimers with Different Chain Stiffness

By means of molecular dynamics simulations of model dendrimers, we analyze the dependence of the bulk density and molecular packing on the dendrimer molecular weight and intrinsic stiffness. We find that the density is consistently higher in flexible dendrimers than in the rigid ones with a large bending angle. The density values change slightly within the first two generations to reach a plateau. We interpret these results in terms of free volume, showing that the enhanced accessible free volume that characterizes the end-dendron monomers is counterbalanced by the higher number of internal monomers, leading to a constant bulk density for generations larger than three. The added stiffness affects the geometrical properties and the molecular rearrangement of the bulk, reducing the short-range local order and the packing efficiency favoring the dendrimer interpenetration. Our prediction for the bulk density matches and rationalizes experimental and previous all-atom simulation results.

Chemical and photochemical degradation of human hair: A free-volume microprobe study

The microstructural changes in human hair due to chemical and photochemical oxidative processes have been monitored in terms of free volume employing Positron Annihilation Lifetime Spectroscopy (PALS). The results show that upon UV exposure the photosensitive amino acid residues present in the amorphous domains of virgin/bleached hair cross-link under ambient conditions. Further, the bleached hair readily undergoes photodamage in comparison with the virgin hair implying the diminished photoprotective action of the melanin granules within it. Swelling of hair fiber was evident in the early stages of UV exposure (<300 h), bleaching, and humidification subsequent to irradiation. Swelling and cross-linking were the two main processes observed following UV exposure, which oppositely affect the free volume holes size. Supplementary techniques such as DSC and XRD were used to support/extend the interpretation of the PALS results. The UV irradiation resulted in reduction of the average crystallite size in hair, which is attributed to the possible fragmentation of protein domains. The present work is the first positron lifetime measurement on human hair that demonstrates the ability of PALS to provide information on hair damage at molecular level, a vital input for cosmetic industry and applicable to biopolymers research as well.

Free-volume dependent pressure sensitivity of Zr-based bulk metallic glass

Instrumented indentation experiments on a Zr-based bulk metallic glass (BMG) in as-cast, shot-peened and structurally relaxed conditions were conducted to examine the dependence of plastic deformation on its structural state. Results show significant differences in hardness, H, with structural relaxation increasing it and shot peening markedly reducing it, and slightly changed morphology of shear bands around the indents. This effect is in contrast to uniaxial compressive yield strength, σy, which remains invariant with the change in the structural state of the alloys investigated. The plastic constraint factor, C = H/σy, of the relaxed BMG increases compared with that of the as-cast glass, indicating enhanced pressure sensitivity upon annealing. In contrast, C of the shot-peened layer was found to be similar to that observed in crystalline metals, indicating that severe plastic deformation could eliminate pressure sensitivity. Microscopic origins for this result, in terms of shear transformation zones and free volume, are discussed.