Observation Of Phase Separation Research Articles

Moisture effects on Protein—Excipient Interactions in Spray-dried Powders. Nature of Destabilizing effects of Sucrose

The preparation of stable solid protein formulations presents significant challenges. Ultimately, the interactions between incorporated excipients and the pharmaceutical protein determine the formulation stability. In this study, moisture was utilized to probe the interactions between a model protein, trypsinogen, and sucrose in the solid state, following spray drying. Through investigation of the physical properties of the spray-dried formulations, we attempted to elucidate the mechanisms underlying the previously observed1,2 stabilizing and destabilizing effects of the carbohydrate during spray drying. Both dynamic and equilibrium moisture uptake studies indicated the presence of an optimal protein–sugar hydrogen bonding network. At low sucrose contents, a preferential protein–sucrose hydrogen bonding interaction was dominant, resulting in protein stabilization. However, at high carbohydrate concentrations, preferential sugar–sugar interactions prevailed, resulting in a phase separation within the formulation matrix. The preferential incorporation of the sucrose molecules in a sugar-rich phase reduced the actual amount of the carbohydrate available to interact with the protein and thereby decreased the number of effective protein–sucrose contacts. As a consequence, the protein could not be effectively protected during spray drying. We hypothesize that the observed phase separation at this sucrose concentration regime originates from its exclusion from the protein in solution before spray drying, further accompanied by preferential clustering of the sucrose molecules.

Phase separation in fluid additive hard sphere mixtures?

Some years ago, Lebowitz and Rowlinson ‘established’ that phase separation did not occur in fluid mixtures of additive hard spheres. Their analysis was based on the thermodynamic functions of this mixture, obtained from the solution of the Percus-Yevick (PY) equation. At the time, these results were thought to be accurate for all states for which additive hard sphere mixtures were fluid. Recent theoretical work and simulations have shown that the PY radial distribution function between a pair of large spheres is seriously in error when the ratio of the diameters of the large and small spheres becomes large and when the concentration of the large spheres is very small. Thus, a reexamination of the question of phase stability in fluid additive hard sphere mixtures is worthwhile. Indeed, it is found that phase separation is probable in fluid additive hard sphere mixtures when the concentration of the large particles is very dilute. Generally, the coexisting phase is solid. However, under some circumstances, the coexisting phase may be fluid. This result may provide insight into the recently observed phase separation in colloids.

The effects of local stiffness disparity on the surface segregation from binary polymer blends

The surface segregation from free space polymer blends based on purely entropic effects is investigated using computer simulation and integral equation theory. Computer simulations are performed for tangent-hard-sphere chains of length ranging from short 10 bead chains to experimentally realistic 500 bead chains. The chain segments of one species experience a bending potential which is introduced between any two consecutive bonds and this serves to make this component stiffer than the other blend component. Computer simulations and numerical wall polymer reference interaction site model (wall-PRISM) integral equation calculations for finite hard core athermal chains demonstrate that at liquidlike densities the segments of the stiffer polymer always partition to a neutral surface, apparently independent of the length of the polymer chains in question. Although the primary factor affecting this segregation is the better local packing of the stiff chains at the surface, lattice mean-field calculations suggest that local conformational changes in the molecules also favor the stiff chains at the surface under these conditions. Further, nonlocal effects appear to be irrelevant in this context. Recently, field theoretic based models have suggested in the context of an incompressible approximation that stiffness disparity is the underlying cause for the experimentally observed surface segregation of branched molecules from blends of linear and branched hydrocarbon polymers (the branched molecules were considered more ‘‘flexible’’ or ‘‘conformationally smaller’’). The segregation observed in the simulations, however, is both much smaller in magnitude and of the opposite sign to that seen in the field theoretic calculations. Coupled with results of independent work on the bulk behavior of these athermal mixtures, which do not capture the experimentally observed phase separation, we suggest that hydrocarbon blends, at least over the chain lengths examined, cannot be modeled in terms of purely entropic effects, but rather through the incorporation of energetics. Analytic wall-PRISM results for a thread like model of the polymer molecules are also presented, and show that the various approximations made in deriving analytical theories critically affect the magnitude and the sign of the predicted athermal segregation. The connections of our analytical work to recent field theoretic analyses is also discussed.

Evolution of microstructure in nanocrystalline Mo-Cu thin films during thermal annealing

The evolution of microstructure in Mo-Cu thin films during annealing has been investigated by in situ sheet resistance measurements, ex situ x-ray diffraction, and in situ hot-stage as well as conventional transmission electron microscopy. Mo-Cu thin films, deposited on various glass substrates by magnetron sputtering at ∼30 °C, were supersaturated solid solutions of Cu in Mo with a nanocrystalline microstructure. The as-deposited films had large compressive residual stresses owing to the low homologous deposition temperature and low Ar pressure during deposition. Annealing results showed two distinct sets of microstructural changes occurring in the temperature ranges between ∼300 and 500 °C, and ∼525 and 810 °C. In the lower-temperature range, anisotropic growth of nanocrystallites was accompanied by stress relaxation without any observable phase separation. At temperatures greater than ∼525 °C, the metastable solid solution collapsed and Cu precipitated at the grain boundaries. Increasing temperature resulted in the coarsening of Cu precipitates and simultaneous growth of Mo grains. At temperatures greater than ∼700 °C, phase separation and grain growth approached completion.

Poly(ethylene glycol)-induced and temperature-dependent phase separation in fluid binary phospholipid membranes

Exclusion of the strongly hygroscopic polymer, poly(ethylene glycol) (PEG), from the surface of phosphatidylcholine liposomes results in an osmotic imbalance between the hydration layer of the liposome surface and the bulk polymer solution, thus causing a partial dehydration of the phospholipid polar headgroups. PEG (average molecular weight of 6000 and in concentrations ranging from 5 to 20%, w/w) was added to the outside of large unilamellar liposomes (LUVs). This leads to, in addition to the dehydration of the outer monolayer, an osmotically driven water outflow and shrinkage of liposomes. Under these conditions phase separation of the fluorescent lipid 1-palmitoyl-2[6-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) embedded in various phosphatidylcholine matrices was observed, evident as an increase in the excimer-to-monomer fluorescence intensity ratio (IE/IM). Enhanced segregation of the fluorescent lipid was seen upon increasing and equal concentrations of PEG both inside and outside of the LUVs, revealing that osmotic gradient across the membrane is not required, and phase separation results from the dehydration of the lipid. Importantly, phase separation of PPDPC could be induced by PEG also in binary mixtures with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), for which temperature-induced phase segregation of the fluorescent lipid below Tm was otherwise not achieved. In the different lipid matrices the segregation of PPDPC caused by PEG was abolished above characteristic temperatures T0 well above their respective main phase transition temperatures Tm. For 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), DMPC, SOPC, and POPC, T0 was observed at approximately 50, 32, 24, and 20 degrees C, respectively. Notably, the observed phase separation of PPDPC cannot be accounted for the 1 degree C increase in Tm for DMPC or for the increase by 0.5 degrees C for DPPC observed in the presence of 20% (w/w) PEG. At a given PEG concentration maximal increase in IE/IM (correlating to the extent of segregation of PPDPC in the different lipid matrices) decreased in the sequence 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DHPC) > DPPC > DMPC > SOPC > POPC, whereas no evidence for phase separation in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) LUV was observed (Lehtonen and Kinnunen, 1994, Biophys. J. 66: 1981-1990). Our results indicate that PEG-induced dehydration of liposomal membranes provides the driving force for the segregation of the pyrene lipid. In brief, phase separation of PPDPC from the matrix lipid could be attributed to the diminishing effective size of the phosphatidylcholine polar headgroup resulting from its partial dehydration by PEG. This in turn would allow for enhanced van der Waals interactions between the acyl chains of the matrix lipid, which then caused the exclusion of PPDPC due to the perturbing bulky pyrene moiety. Phase separation in DMPC/PPDPC liposomes was abolished by the inclusion of 25 mol % cholesterol and to a lesser extent by epicholesterol.

Absence of phase separation effects in blends of linear polyethylene fractions of differing molecular weight

Blends of linear polyethylenes of differing molecular weights ( MWs) have been studied to try to determine whether there is any observable phase separation in the melt. Using four linear polyethylene fractions, of MWs between 2 × 10 6 and 2.5 × 10 3, blends were prepared and four blend systems investigated, the two high MW polymers being blended with each of the two lower MW materials in turn. The blends were studied by transmission electron microscopy and differential scanning calorimetry, techniques previously used to study blends of linear with branched polyethylenes. In these systems, for some compositions of blends of linear with branched polyethylene, quenched from some temperatures, phase separation on a scale of micrometres has been recorded. In contrast, no indications of phase separation were observed on examination of the blends of linear with linear polyethylenes. From this it follows that if there is any liquid-liquid phase separation in linear with linear polyethylene blends, taking place as a result of molecular weight differences, it cannot be detected by the methods used to detect liquid—liquid phase separation in linear with branched polyethylene blends; and, conversely, the phase separation observed in linear with branched polyethylene blend systems does not take place as a result of molecular weight difference alone.

Monophasic silica glasses with large neodymia concentration

Abstract The use of one ideal candidate for high-powered lasers, neodymia-silica glass, is unfortunately limited by phase separation into undesirable Nd-rich crystalline droplets within an Nd-deficient matrix. Plasma CVD and sol-gel process using NdCl3 or Nd(NO3)3 as dopant both failed to produce single-phase Nd2O3SiO2 glass when neodymia exceeded 5 wt%. Using Nd(COOCH3)3 and acetic acid hydrolysed tetraethyl orthosilicate, the present authors produced monolithic glasses 10 (wt%) Nd2O3 · 90 SiO2 with no observable phase separation. Nd chloride doped gels, where the neodymium concentration increased from the interior to the surface, were much poorer in chemical homogeneity than Nd acetate doped gels of equivalent composition. Free salts of neodymium are responsible for causing the concentration gradient.

Observation of phase separation in Hg1−xCdxTe solid solutions by low incident angle x-ray diffraction

The low incident angle (surface analysis) and the conventional wide angle (bulk analysis) x-ray diffraction techniques were employed to investigate the existence of a miscibility gap in the Hg1−xCdxTe system. Samples of initial composition Hg0.46Cd0.54Te were annealed at 140 and 400°C, respectively, for four weeks. The diffraction planes (531) and (642) have been selected for the x-ray diffraction analysis. The results of this work provide the first, direct experimental evidence for the existence of a miscibility gap at lower temperature in the Hg1−xCdxTe system. The phase separation occurs primarily in a thin surface layer at 140°C and is reversible after annealing at 530°C. The compositions of the two compounds at the tie-line at 140°C are Hg0.22Cd0.78Te and Hg0.63Cd0.37Te.

Anisotropic binders for polymer/liquid crystal dispersions

AbstractThe synthesis and phase behavior of linear and crosslinked side‐group epoxy polymers are described. These polymers are used in dispersons with low‐molecular‐weight liquid crystals, and the observation of phase separation in these systems is demonstrated.

First-order phase transition between orthorhombic phases in YBa2Cu3Oz.

We investigate the effects of elastic interactions and the associated orthorhombic distortion on the structural phase transitions in ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{\mathit{z}}$. Starting from a two-dimensional Ising model previously demonstrated to describe accurately the high-temperature phase boundaries, we show by means of Landau theory that the square-rectangular symmetry breaking may lead to a first-order transition between the orthorhombic single- and double-cell phases at low temperatures. This explains experimental observations of phase separation between orthorhombic phases, while retaining the simplicity and predictive power of the original model.

Radiation induced phase separation in irradiated PTFE

The radiation induced phase separation in PTFE as shown by the observation of separation of its melting curves was investigated in this work. The observed phase separation was found to depend on irradiation temperature and explained as being duo to radiation induced increase in disorder of its crystalline region.

Phase separation in amorphous ErNi2Hx prepared by hydrogenation

X-ray diffraction and observations of phase separation are reported in a hydrogen-induced amorphous ErNi2 alloy. Two separate diffuse maxima in x-ray diffraction and two principal halos in electron diffraction, which are evidence of phase separation into two amorphous states, are observed at hydrogenation conditions of 50 atm H2 and elevated temperatures. The phenomenon of phase separation is manifest with increasing hydrogenation temperature. The compositions of both phases are estimated by comparing the nearest-neighbor distances calculated by using the Ehrenfest relation with all possible atomic distances in amorphous ErNi2 hydride. These distances are calculated by assuming that the configurational atomic arrangement in the amorphous phase is composed of tetrahedral units. The compositions of the two phases seem to correspond to an Er-rich phase (mixture of 4-Er and 3Er+1Ni tetrahedra) and a Ni-rich phase (mixture of 4-Ni and 1Er+3Ni tetrahedra). This phase separation may be caused by the motion of Ni atoms over short distances.

Effect of nonadsorbing polymers on the rheology of a concentrated nonaqueous dispersion

The rheology of a poly(methyl methacrylate) (PMMA) latex stabilized with poly(12-hydroxystearic acid) and dispersed in dodecane at a volume fraction of 0.42 was observed to deviate from near Newtonian behavior upon the addition of polyisobutylene (PIB) at high and low molecular weights, 380,000 and 2,000, respectively. The high molecular weight PIB gave the dispersion a predicted depletion-flocculated behavior, with observable phase separation and non-Newtonian shear thinning rheology, as a consequence of the additional attractive particle interaction component. Added low molecular weight PIB, however, gave comparatively much stronger non-Newtonian behavior with no observable phase separation. This behavior was observed in a region of polymer molecular weights and size comparable to that of the steric layer. The results are consistent with a steric-elastic repulsion arising from the compression of the nonadsorbing polymer chains at high particle volume fraction and not with an attractive term due to depletion flocculation.

Liquid crystalline polyester and polysulphone mixtures: observation of phase separation and aggregation

As a preliminary investigation, the flexibility of a wholly aromatic paralinked random copolyester is studied from measurements of the radius of gyration by small angle X-ray scattering and of the hydrodynamic radius by viscosimetry. In this way, the persistence length has also been evaluated. The ability of this polyester to be oriented by means of a magnetic field (as shown by 1H n.m.r.) confirms the high flexibility of the polyester backbone. In concentrated solutions, the polyester aggregates. An indication of the aggregate size is inferred from the wide angle light scattering (WALS) study. When polysulphone is added to these mixtures, the demixing process is also preceded by aggregation. The structure of these aggregates is investigated by WALS and indicates that a state of ordering exists which is a precursor to that found in the mixtures in the solid state.

On the development of a model for predicting phase separation phenomena in dividing two-phase flow

A model to predict the dividing flow characteristics for annular flow in a T-junction is proposed consisting of mixture and vapour phase continuity equations, two pressure change correlations and a closure relationship. The pressure change from the inlet through the run of the T is modelled by way of a balance of axial momentum at the junction based on a separated flow assumption. The branch pressure change is modelled using a balance of mechanical energy for the branching flow consisting of reversible and irreversible components. The closure relationship links the phase separation characteristics with the junction pressure changes. It involves a balance between pressure and inertia forces within the junction volume defining a dividing surface for each phase between the run and branch flows. The branch quality is then determined using a well-defined inlet flow distribution. The model is capable of predicting the experimentally observed phase separation characteristics from three independent studies of annular/steam—water and air-water flow in dividing T-junctions.

The analysis of phase separation and phase distribution phenomena using two-fluid models

It is the purpose of this paper to investigate the ability of multidimensional two-fluid models to predict the observed phase separation and lateral phase distribution phenomena. It will be shown that such phenomena can be predicted once all significant physical mechanisms have been adequately modelled. Indeed, this paper shows, for the first time, that closed-loop predictions are possible of multidimensional phase distribution and phase separation in two-phase flows.

The nasicon-type titanium phosphates Ati2(PO4)3 (A=Li, Na) as electrode materials

Lithium and sodium have been intercalated in LiTi 2 (PO 4 ) 3 and NaTi 2 (PO 4 ) 3 respectively. Despite the low electronic conductivity of the NASICON framework the intercalation can be realized either chemically or electrochemically. The electrochemical study shows the reversibility of the process and the existence of large biphased domains in both systems. The observed phase separation reactions result from Li + (Na + ) and e − migration without skeleton bond breaking and recombination. The large hexagonal c -parameter of Li 3 Ti 2 (PO 4 ) 3 results from a peculiar lithium ion distribution (M(1) empty, M(2) fully occupied) as shown by neutron diffraction.

Observation of Phase Separation in Lead Containing ZrF<sub>4</sub> - Based Glasses

Observation of Phase Separation in Lead Containing ZrF<sub>4</sub> - Based Glasses

Ca 2+ induced phase separations in phospholipid mixtures

We have probed the character of the observed phase separation in mixtures of phosphatidylcholines (PC) and/or phosphatidylethanolamines (PE) in the presence of CaCl 2 solutions. Egg yolk phosphatidylethanolamine (EYPE) and a 1:1 molar ratio of dioleoylphosphatidylcholine/dioleoylphosphatidylethanolamine (DOPC/DOPE) were observed to undergo phase separation in CaCl 2 solutions, as was previously observed for egg yolk phosphatidylcholine (EYPC) (L.J. Lis et al. Biochemistry, 20 (1981) 1771–1777). However, the mixed chain lipid, palmitoyloleoyl-PC, yielded only a single phase in water or CaCl 2 solution. We hypothesize that two lipid species are necessary for the observed phase separation to occur, but that the separation itself is not a function of the individual lipid species, but of the mixture.

Magnetic Eiaxaticn and Structural Transfor4Aticn in Metallic Glasses

ABSTRACTCurrent understanding of the local atomic structure of amorphous materials is reviewed. Sane results of probing short—range order by selected techniques are cited to illustrate the degree of uniformity that exists on a local scale. Observations of phase separation and phase changes are described with particular emphasis on a temperature driven, reversible transformation of the local structure observed magnetically in several cobalt—base glasses. The manifestations and implications of such transformations within the glassy state are examined. Several examples pointing to quasi—crystalline and to non—crystalline (non—space filling) local structures are given.