Difference In Nucleation Rate Research Articles

Synergistic Control of Nonlinear Growth Kinetics and Nucleation Kinetics in the Concomitant Crystallization of Aripiprazole as Reflected by the Ostwald Ratio

Some polycrystalline drugs are subject to concomitant polymorphism during the manufacturing process, resulting in large batch-to-batch variation and reduced drug bioavailability. Most existing studies on concomitant polymorphism have focused only on differences in nucleation kinetics and lacked analysis of the role of growth processes in polymorph control. Herein, we conducted a systematic study on the concomitant crystallization of aripiprazole Form III and Form V under the influence of thermodynamic and kinetic factors employing thermal analysis with the Ostwald ratio as a medium. It shows that the nucleation and growth rates of both forms cross over with increasing supersaturation. The comparison between the polymorph composition computed by the Ostwald ratio and the experiments highlights the considerable influence of crystal growth on the formation of concomitant polymorphism. The effect of crystal growth at lower supersaturation is indeed minimal due to the large difference in nucleation rates, but as the supersaturation increases, the difference in nucleation rates becomes smaller and the growth rate ratio gradually becomes a key factor. The images plotted with initial concentration and crystallization temperature further demonstrate that the introduction of actual nonlinear growth kinetics can lead to improved computation accuracy of the Ostwald ratio. This work provides evidence for the application of the Ostwald ratio in the design of batch crystallization for a concomitant system.

Mixed Hydrate Nucleation: Molecular Mechanisms and Cage Structures.

The molecular-level details of the formation of mixed gas hydrates remain elusive despite their significance for a variety of scientific and industrial applications. In this study, extensive molecular simulations have been performed to examine the behavior of CH4/H2S mixed hydrate nucleation utilizing two different simulation setups varying in compositions and temperatures. The observed behavior exhibits similar phenomenology across the various systems once differences in nucleation rates and guest uptake are accounted for. We find that CH4 is always enriched in the hydrate phase while the aqueous phase is enriched in H2S. Even with H2S as a minor component (i.e., 10% mole fraction), the system can mirror the overall nucleation kinetics of pure H2S hydrate systems with CH4-dominant nuclei. Through analyses of cages and their transitions, nonstandard cages, particularly those with 12 faces (e.g., 51062), have been found to be key intermediate cage types in the early stage of nucleation. Additionally, we present previously unreported cage types comprising heptagonal faces (e.g., 596271) as having a significant role in the early-stage gas hydrate structural transitions.

Homogeneous water nucleation: Experimental study on pressure and carrier gas effects.

Homogeneous nucleation of water is investigated in argon and in nitrogen at about 240 K and 0.1 MPa, 1 MPa, and 2 MPa by means of a pulse expansion wave tube. The surface tension reduction at high pressure qualitatively explains the observed enhancement of the nucleation rate of water in argon as well as in nitrogen. The differences in nucleation rates for the two mixtures at high pressure are consistent with the differences in adsorption behavior of the different carrier gas molecules. At low pressure, there is not enough carrier gas available to ensure the growing clusters are adequately thermalized by collisions with carrier gas molecules so that the nucleation rate is lower than under isothermal conditions. This reduction depends on the carrier gas, pressure, and temperature. A qualitative agreement between experiments and theory is found for argon and nitrogen as carrier gases. As expected, the reduction in the nucleation rates is more pronounced at higher temperatures. For helium as the carrier gas, non-isothermal effects appear to be substantially stronger than predicted by theory. The critical cluster sizes are determined experimentally and theoretically according to the Gibbs-Thomson equation, showing a reasonable agreement as documented in the literature. Finally, we propose an empirical correction of the classical nucleation theory for the nucleation rate calculation. The empirical expression is in agreement with the experimental data for the analyzed mixtures (water-helium, water-argon, and water-nitrogen) and thermodynamic conditions (0.06 MPa-2 MPa and 220 K-260 K).

Microstructural evolution and mechanical behavior of phase reversion-induced bimodal austenitic steels

The present study aimed at achieving excellent mechanical properties in austenitic stainless steel by the design of bimodal (BM) microstructure fabricated through cold rolling and reverse annealing. The evolution of the BM microstructure during reverse annealing was investigated in detail. Moreover, the strengthening mechanism and the work-hardening behavior of BM steels were also analyzed. It was found that when the annealing temperature was below 634 °C, the reversion of strain-induced martensite (SIM; approximately 80%) into austenite (α' → γ) was mainly controlled by the diffusion mechanism. However, when the annealing temperature exceeded 634 °C, the reversion of SIM was gradually controlled by the shearing mechanism due to an increase in the driving force for shearing reversion. When annealing was carried out at 800 °C for 1–1000 s, the BM microstructure was successfully obtained because of the differences in nucleation rate and stored energy between the reversed austenite zone (approximately 80%) and the deformed austenite zone (approximately 20%) during recrystallization. The yield strengths (YS; 658–775 MPa) and the tensile strength (TS; 1157–1183 MPa) of the as-prepared BM steels were significantly improved as compared to those of the solid-solution-treated (coarse-grained; CG) steel (YS = 332 MPa and TS = 1022 MPa). Furthermore, the effects of twinning-induced plasticity (TWIP) and multi-stage transformation-induced plasticity (TRIP) (caused by the BM microstructure) contributed to strong work-hardening ability and high ductility. The uniform elongation and the total elongation of the as-obtained BM steels were measured as ~45% and ~55.5%, respectively.

Influence of water vapor pressure on the induction period during Li 2SO 4·H 2O single crystals dehydration

The dehydration of Li 2SO 4·H 2O single crystals at 80 °C has been studied by means of both isothermal thermogravimetry at 2.6, 3.6 and 4.6 hPa of water vapor and environmental scanning electron microscope. Thermogravimetric experiments allowed the determination of induction periods. Distributions of these isoconversion induction periods for a large number of single crystals showed that increasing the water vapor pressure produced a longer induction period. Moreover, the shape of the distributions of the induction periods over a large number of single crystals changed from one mode at 2.6 hPa to two modes at 3.6 and 4.6 hPa. Using an environmental scanning electron microscope, this result could be attributed to differences in nucleation rates at edges and faces of the single crystals.

Formulation and Stability of Itraconazole and Odanacatib Nanoparticles: Governing Physical Parameters

The successful formulation of itraconazole and odanacatib into nanoparticle form with diameters of 145 and 350 nm, respectively, using rapid, block copolymer-directed precipitation is presented. These are the smallest stable nanoparticles that have been reported for these compounds. The difference in size of the nanoparticles for the two compounds is explained by the difference in nucleation rate and its dependence on supersaturation. The conditions for stability after formation are presented: storage at 5 degrees C and removal of residual processing solvent. These requirements are explained in terms of solute solubility and its dependence on both temperature and solvent concentration. The theory of Ostwald ripening provides the framework for understanding the differences in stability observed for the two compounds. The dynamics of the hydrophobic polymer block plays a major role in long-term stability as demonstrated by the behavior of nanoparticles stabilized by poloxamer vs polystyrene-b-polyethylene oxide polymers.

Updated H2SO4‐H2O binary homogeneous nucleation look‐up tables

The calculated rates of H2SO4‐H2O binary homogeneous nucleation (BHN), which is the only nucleation mechanism currently widely used in global aerosol models, are well known to have large uncertainties. Recently, we have reduced the uncertainties in the BHN rates on the basis of a kinetic quasi‐unary nucleation (KQUN) model, by taking into account the measured bonding energetics of H2SO4 monomers with hydrated sulfuric acid dimers and trimers. The uncertainties were further reduced by using two independent measurements to constrain the equilibrium constants for monomer hydration. In this paper, we present updated BHN rate look‐up tables derived from the improved KQUN model which can be used by anyone to obtain the BHN rates under given conditions. The look‐up tables cover a wide range of key parameters that can be found in the atmosphere and laboratory studies, and their usage significantly reduces the computational costs of the BHN rate calculations, which is critical for multidimensional modeling. The look‐up tables can also be used by those involved in experiments and field measurements to quickly assess the likeliness of BHN. For quick application, one can obtain the BHN rates and properties of critical clusters by browsing through the tables. A comparison of results based on the look‐up tables with those from widely used classical BHN model indicates that, in addition to several orders of magnitude difference in nucleation rates, there also exists substantial difference in the predicted numbers of sulfuric acid molecules in the critical clusters and their dependence on key parameters.

Influence of thermostats and carrier gas on simulations of nucleation

We investigate the influence of carrier gas and thermostat on molecular dynamics (MD) simulations of nucleation. The task of keeping the temperature constant in MD simulations is not trivial and an inefficient thermalization may have a strong influence on the results. Different thermostating mechanisms have been proposed and used in the past. In particular, we analyze the efficiency of velocity rescaling, Nose-Hoover, and a carrier gas (mimicking the experimental situation) by extensive MD simulations. Since nucleation is highly sensitive to temperature, one would expect that small variations in temperature might lead to differences in nucleation rates of up to several orders of magnitude. Surprisingly, the results indicate that the choice of the thermostating method in a simulation does not have--at least in the case of Lennard-Jones argon--a very significant influence on the nucleation rate. These findings are interpreted in the context of the classical theory of Feder et al. [Adv. Phys. 15, 111 (1966)] by analyzing the temperature distribution of the nucleating clusters. We find that the distribution of cluster temperatures is non-Gaussian and that subcritically sized clusters are colder while postcritically sized clusters are warmer than the bath temperature. However, the average temperature of all clusters is found to be always higher than the bath temperature.

Theoretical analysis of calcium phosphate precipitation in simulated body fluid

The driving force and nucleation rate of calcium phosphate (Ca-P) precipitation in simulated body fluid (SBF) were analyzed based on the classical crystallization theory. SBF supersaturation with respect to hydroxyapatite (HA), octacalcium phosphate (OCP) and dicalcium phosphate (DCPD) was carefully calculated, considering all the association/dissociation reactions of related ion groups in SBF. The nucleation rates of Ca-P were calculated based on a kinetics model of heterogeneous nucleation. The analysis indicates that the nucleation rate of OCP is substantially higher than that of HA, while HA is most thermodynamically stable in SBF. The difference in nucleation rates between HA and OCP reduces with increasing pH in SBF. The HA nucleation rate is comparable with that of OCP when the pH value approaches 10. DCPD precipitation is thermodynamically impossible in normal SBF, unless calcium and phosphate ion concentrations of SBF increase. In such case, DCPD precipitation is the most likely because of its highest nucleation rates among Ca-P phases. We examined the influences of different SBF recipes, interfacial energies, contact angle and molecular volumes, and found that the parameter variations do not have significant impacts on analysis results. The effects of carbonate incorporation and calcium deficiency in HA were also estimated with available data. Generally, such apatite precipitations are more kinetically favorable than HA.

Simulation of atmospheric nucleation mode: A comparison of nucleation models and size distribution representations

Atmospheric particle formation and growth were investigated using different nucleation models and size distribution representations. Nucleation was modeled using recently developed parameterizations for binary nucleation of water and sulphuric acid and ternary nucleation of water, sulphuric acid, and ammonia. A comparison with older nucleation parameterizations, combined with full aerosol dynamics, demonstrated that the difference in nucleation rate (1–2 orders of magnitude) is clearly reflected in the resulting total particle concentration. A comparison of binary and ternary nucleation schemes showed that above 240 K the ternary nucleation rate exceeds the binary by over 10 orders of magnitude, indicating that in most cases, at lower tropospheric conditions, only ternary nucleation can be relevant. In addition, the performance of aerosol dynamics models applying either a multimodal monodisperse or a fixed sectional size distribution representation was evaluated against a molecular resolution model, which follows the changes in the nucleation mode particle size distribution molecule by molecule. Regarding total number concentration, the sectional method converged to the molecular resolution approach when increasing the number of size sections. With strong condensational growth, however, numerical diffusion problems were evident. Overall, the performance of the sectional method with low number of sections was not satisfactory. The monodisperse method gave very good results, at least in terms of total number, when the background modes were set to match the condensation sinks of respective lognormal modes. On the basis of our study the multimodal monodisperse method seems to be a possible candidate when selecting the size distribution approach for large‐scale atmospheric models.

Comparison of Titania Particles Between Oxidation of Titanium Tetrachloride and Thermal Decomposition of Titanium Tetraisopropoxide

Thermal decomposition of TTIP was compared with oxidation of TiCl 4 in morphology and primary particle size of produced TiO 2 particles in a tubular reactor 2.7 cm in diameter and 54 cm in length under equal rate constants. The reactor temperature was varied from 850 to 1000°C for TiCl 4 oxidation and from 492 to 579°C for TTIP decomposition. The lower and upper limits of decomposition temperature for TTIP were determined so that the rate constants become equal, at corresponding limits, between TiCl 4 oxidation and TTIP decomposition. In order to maintain constant concentration with variation of reactor temperature, the flow rate of dilution gas was adjusted to compensate for the volume change of gas with temperature. The precursor concentration at the reaction condition was in the range of 1.09 2 10 m 6 to 1.09 2 10 m 5 mol/L, and the residence time of 3.1 to 10.8 s was based on the reactor set temperature. Particles from TTIP were spherical, while those from TiCl 4 were polyhedral. A considerable fraction of the precursor admitted to the reactor was consumed on the tube wall by surface reaction to form a zone coated with TiO 2 . The loss of precursor to the wall was greater with TiCl 4 oxidation. The particle size was, however, larger by 20% with TiCl 4 oxidation. By replacing the straight reaction tube with a concentric tube, the loss could be reduced, thereby increasing the amount of TiCl 4 available for particle formation significantly; the particle size was similar, however. With the straight tube a mixture of TiCl 4 and oxygen entered the reactor and the reaction occurred over the gradual increase from 650°C to a reactor set temperature of 900°C. With the concentric tube, the reactants had been preheated separately and then brought into contact right at the set temperature. The difference in the history of temperature for reaction may have brought about a difference in nucleation rate and consequently yielded particles of similar size. By analyses of BET surface area, X-ray diffraction patterns, and thermogravimetric data, TiO 2 particles from both routes were nearly nonporous, showed anatase peaks in majority, and contained no appreciable volatiles.

Underlayer work function effect on nucleation and film morphology of chemical vapor deposited aluminum

The dependence of early stage of dimethylaluminum hydride (DMAH)-sourced aluminum chemical vapor deposition on underlayer material was investigated. Identical process conditions were used to deposit the aluminum on TiN, TaN and Ti-W surfaces. Surface coverage and particle densities of aluminum deposited on TiN were much greater than those deposited on Ti-W or TaN. Work function measurements performed on the three metal surfaces suggest that the difference in nucleation rate on TiN compared to TaN and Ti-W is due its increased ability to donate electrons to the DMAH decomposition process.

Different WASP family proteins stimulate different Arp2/3 complex-dependent actin-nucleating activities

Background: Assembly and organization of actin filaments are required for many cellular processes, including locomotion and division. In many cases, actin assembly is initiated when proteins of the WASP/Scar family respond to signals from Rho family G proteins and stimulate the actin-nucleating activity of the Arp2/3 complex. Two questions of fundamental importance raised in the study of actin dynamics concern the molecular mechanism of Arp2/3-dependent actin nucleation and how different signaling pathways that activate the same Arp2/3 complex produce actin networks with different three-dimensional architectures?Results: We directly compared the activity of the Arp2/3 complex in the presence of saturating concentrations of the minimal Arp2/3-activating domains of WASP, N-WASP, and Scar1 and found that each induces unique kinetics of actin assembly. In cell extracts, N-WASP induces rapid actin polymerization, while Scar1 fails to induce detectable polymerization. Using purified proteins, Scar1 induces the slowest rate of nucleation. WASP activity is 16-fold higher, and N-WASP activity is 70-fold higher. The data for all activators fit a mathematical model in which one activated Arp2/3 complex, one actin monomer, and an actin filament combine into a preactivation complex which then undergoes a first-order activation step to become a nucleus. The differences between Scar and N-WASP activity are explained by differences in the rate constants for the activation step. Changing the number of actin binding sites on a WASP family protein, either by removing a WH2 domain from N-WASP or by adding WH2 domains to Scar1, has no significant effect on nucleation activity. The addition of a three amino acid insertion found in the C-terminal acidic domains of WASP and N-WASP, however, increases the activity of Scar1 by more than 20-fold. Using chemical crosslinking assays, we determined that both N-WASP and Scar1 induce a conformational change in the Arp2/3 complex but crosslink with different efficiencies to the small molecular weight subunits p18 and p14.Conclusion: The WA domains of N-WASP, WASP, and Scar1 bind actin and Arp2/3 with nearly identical affinities but stimulate rates of actin nucleation that vary by almost 100-fold. The differences in nucleation rate are caused by differences in the number of acidic amino acids at the C terminus, so each protein is tuned to produce a different rate of actin filament formation. Arp2/3, therefore, is not regulated by a simple on-off switch. Precise tuning of the filament formation rate may help determine the architecture of actin networks produced by different nucleation-promoting factors.

Characterization of thermally annealed thin silicon films on insulators by Raman image measurement

The characterization of the crystallinity by Raman image measurements has been made on thin silicon films on insulators, which are deposited by low pressure chemical vapor deposition using silane (SiH4) and disilane (Si2H6) as gas sources and are subsequently thermally annealed. The degree of crystallization by thermal annealing has been quantitatively evaluated by comparing the integrated Raman scattering intensity of the polycrystalline band and the amorphous band. The volume fraction of the crystalline component in samples grown with silane is larger than that grown with disilane for the same annealing time. Raman images of these thin silicon films reveal that the grain size in samples grown with disilane is a few microns, being bigger than that grown with silane. The affect of the source gas on the grain size of crystallites and on the volume fraction of the crystalline component in the films is attributed to the difference in nucleation rate for two kinds of the films during annealing.

Geology and petrogenesis of the Straumsvola nepheline syenite complex, Dronning Maud Land, Antarctica

AbstractThe 170 Ma Straumsvola nepheline syenite complex in western Dronning Maud Land, Antarctica, is located on the eastern edge of the Penck-Jutul Trough, a major tectonic feature which may be a Palaeozoic-Mesozoic rift system. The 5 km diameter pluton consists entirely of nepheline syenite and can be divided into two volumetrically important units: a relatively structureless outer zone which is overlain by a layered zone. The latter exhibits continuous rhythmic alternations of layers containing different proportions of alkali feldspar to amphibole+Na-rich pyroxene+biotite+nepheline throughout its 350 m thickness. The mafic zone is a volumetrically minor unit which unconformably overlies the layered zone and consists almost entirely of mafic minerals and nepheline. The layered zone shows no systematic stratigraphic variation in major or trace composition or mineral chemistry which is interpreted as being due to a combination of migration of intercumulus liquid and action of deuteric fluids. The remarkably constant thickness of successive layers throughout the layered zone suggests that layering resulted from an internally self-regulating process(es). The layering is defined by changing proportions of alkali feldspar to mafic minerals+nepheline which is consistent with layering being caused by differences in nucleation rate during eutectic crystallization. Dykes associated with the complex show wide-ranging compositions and include both over-and undersaturated types. Low σ18O values of the nepheline syenites (mean 5.9%, n = 9) suggest that the magma from which the nepheline syenites crystallized was mantlederived. Peralkaline microgranite dykes have higher σ18O values (mean 7.3%, n = 4) and it is suggested that they are either undersaturated liquids contaminated by siliceous crust, or derived by partial melting of partly fenitized gneiss. Oxygen isotope ratios of the surrounding gneiss indicate that the intrusion of the nepheline syenite did not cause extensive circulation of meteoric or magmatic hydrothermal fluids.

Measurement and scale‐up of secondary nucleation kinetics for the potash alum‐water system

AbstractSecondary nucleation kinetics for potash alum in draft‐tube baffled crystallizers have been determined from steady state crystal size distributions measured down to about 5 μm. Differences in nucleation rates were found for crystallizers of similar geometry but different capacity. Models relating the frequency of crystal/propeller collisions to crystallizer geometry and operating parameters were compared. In general, these successfully accounted for the observed differences in nucleation rates.

Mechanical alloying of IN-738

Mechanical alloying has been applied to produce a dispersion-strengthened superalloy IN-738 containing 1.5 wt pct Y2O3. Annealing of extrusion bars above the recrystallization temperature of 1160°C can be described by three stages of recrystallization:finegrain; isotropic coarse-grain; and fibrous coarse grain growth. A maximum grain length of 550 μm and a maximum grain aspect ratio of 4.8 have been obtained for an alloy, which had been extruded at 1100°C and annealed at 1280°C and 1270°C for 3 h, respectively. The three stages of grain growth are explained in terms of recovery, differences in nucleation rate and dispersoid concentration in the two normal directions and release in stored cold work. Secondary recrystallization can be excluded as a mechanism for fibrous grain coarsening. Dispersion-strengthened IN-738, heat treated to a coarse elongated grain structure, has both high intermediate temperature strength and high elevated temperature strength. The creep strength at 1000°C exceeds that of cast or directionally solidified IN-738 after 300 h service life. The failure mechanism at elevated temperature is intergranular fracture along transverse grain boundaries, nucleated by cavities that form during grain boundary sliding. Nucleation of voids is retarded in the creep specimens due to diffusional accommodation of grain boundary sliding. A depletion of surface zones of chromium, aluminum and titanium contributes to initiation of creep failure at 1000°C.