Nucleation Induction Time Research Articles

Salt scales on process equipment: Measurement of the induction time for calcium carbonate nucleation

AbstractCalcium carbonate and calcium sulphate scales can lead to an increase in running costs, can decline or stop the flow of fluids, and can cause early equipment fouling and failure in several industrial sectors, such as oil industries and desalted water production plants. A way to delay or hinder the formation of these salts is to use a proper additive, able to modify the nucleation kinetic increasing the induction times for salt nucleation. However, in order to properly understand the overall phenomenon it is worth defining the scenario of calcium sulphate and carbonate salts nucleation kinetics in the absence of any additive. The scope of the work is to measure, with a high resolution and in‐line laser technique previously devised, the induction times for calcium carbonate nucleation on a lab scale plant. The experiments have been carried out at temperatures of 25 °C and 35 °C, with a supersaturation ratio S varying in the interval 2–210, and show that as expected the measured induction times for calcium carbonate nucleation strongly decrease while increasing supersaturation for each fixed temperature, outlining a wide metastable region. The obtained values have been used to evaluate the interfacial tension between salt crystals and mother solution (109.3 mJ/m2 for T = 25 °C and γsl = 95.7 mJ/m2 for T = 35 °C) that are in good agreement with other available literature values.

Nucleation inhibition despite lower glass viscosities? - Effect of the B2O3, Na2O and K2O addition on the crystallization behavior of lithium disilicate glasses

Abstract Stoichiometric lithium disilicate glasses were doped with up to 2 mol% B 2 O 3 , Na 2 O or K 2 O and the crystallization kinetics were determined as a function of the temperature using in situ hot-stage microscopy. The additives lead to a decrease of the glass viscosities in the studied temperature range with the exception of the boron-containing samples which show slightly higher viscosities in the nucleation range. While in the boron-containing samples, lithium disilicate solid solutions precipitate during thermal treatment, in the other samples a mixture of lithium disilicate, lithium metasilicate and cristobalite was detected. The steady-state nucleation rates decrease by up to one order of magnitude and especially in the case of the additive B 2 O 3 , the induction times for nucleation are remarkably longer. While the additives B 2 O 3 and K 2 O lead to a decrease of the crystal growth velocities, in case of Na 2 O, the contrary effect can be noticed. Possible reasons for the observed effects are discussed.

Heterogeneous Nucleation of an n-Alkane on Tetrahedrally Coordinated Crystals.

Heterogeneous nucleation refers to the propensity for phase transformations to initiate preferentially on foreign surfaces, such as vessel walls, dust particles, or formulation additives. In crystallization, the form of the initial nucleus has ramifications for the crystallographic form, morphology, and properties of the resulting solid. Nevertheless, the discovery and design of nucleating agents remains a matter of trial and error because of the very small spatiotemporal scales over which the critical nucleus is formed and the extreme difficulty of examining such events empirically. Using molecular dynamics simulations, we demonstrate a method for the rapid screening of entire families of materials for activity as nucleating agents and for characterizing their mechanism of action. The method is applied to the crystallization of n-pentacontane, a model surrogate for polyethylene, on the family of tetrahedrally coordinated crystals, including diamond and silicon. A systematic variation of parameters in the interaction potential permits a comprehensive, physically based screening of nucleating agents in this class of materials, including both real and hypothetical candidates. The induction time for heterogeneous nucleation is shown to depend strongly on crystallographic registry between the nucleating agent and the critical nucleus, indicative of an epitaxial mechanism in this class of materials. Importantly, the severity of this registry requirement weakens with decreasing rigidity of the substrate and increasing strength of attraction to the surface of the nucleating agent. Employing this method, a high-throughput computational screening of nucleating agents becomes possible, facilitating the discovery of novel nucleating agents within a broad "materials genome" of possible additives.

Theoretical framework for predicting inorganic fouling in membrane distillation and experimental validation with calcium sulfate

A methodology for predicting scaling in membrane distillation (MD), which considers thermodynamics, kinetics, and fluid mechanics, is developed and experimentally validated with calcium sulfate. The theory predicts the incidence of scaling as a function of temperature, concentration, and flow conditions by comparing the nucleation induction time to the residence time and applying an experimental correction factor. The relevant residence time is identified by considering a volume of solution near the membrane surface that contains enough ions to form a nucleus of critical size. The theory is validated with fouling experiments using calcium sulfate as a model scalant over a range of temperatures (40–70°C), saturation indices, and flow rates. Although the model is validated with a bench-scale MD system, it is hoped to be compatible with large-scale systems that may have significant changes in concentration, temperature, and flow rate along the flow direction. At lower temperatures, the saturation index can be as high as 0.4–0.5 without scaling, but the safe concentration limit decreases with increasing temperature. Increasing the feed flow rate reduces concentration polarization and fluid residence time, both of which decrease the likelihood of fouling. The model is translated into easily readable maps outlining safe operating regimes for MD. The theory and maps can be used to choose safe operating conditions in MD over a wide range of conditions and system geometries.

Calcium carbonate scales on process equipment: A measure of the induction time for nucleation

Calcium carbonate scales on process equipment: A measure of the induction time for nucleation

Natural Gas Evolution in a Gas Hydrate Melt: Effect of Thermodynamic Hydrate Inhibitors.

Natural gas extraction from gas hydrate sediments by injection of hydrate inhibitors involves the decomposition of hydrates. The evolution of dissolved gas from the hydrate melt is an important step in the extraction process. Using classical molecular dynamics simulations, we study the evolution of dissolved methane from its hydrate melt in the presence of two thermodynamic hydrate inhibitors, NaCl and CH3OH. An increase in the concentration of hydrate inhibitors is found to promote the nucleation of methane nanobubbles in the hydrate melt. Whereas NaCl promotes bubble formation by enhancing the hydrophobic interaction between aqueous CH4 molecules, CH3OH molecules assist bubble formation by stabilizing CH4 bubble nuclei formed in the solution. The CH3OH molecules accumulate around the nuclei leading to a decrease in the surface tension at their interface with water. The nanobubbles formed are found to be highly dynamic with frequent exchange of CH4 molecules between the bubble and the surrounding liquid. A quantitative analysis of the dynamic behavior of the bubble is performed by introducing a unit step function whose value depends on the location of CH4 molecules with respect to the bubble. It is observed that an increase in the concentration of thermodynamic hydrate inhibitors reduces the exchange process, making the bubble less dynamic. It is also found that for a given concentration of the inhibitor, larger bubbles are less dynamic compared to smaller ones. The dependence of the dynamic nature of nanobubbles on bubble size and inhibitor concentration is correlated with the solubility of CH4 and the Laplace pressure within the bubble. The effect of CO2 on the formation of nanobubble in the CH4-CO2 mixed gas hydrate melt in the presence of inhibitors is also examined. The simulations show that the presence of CO2 molecules significantly reduces the induction time for methane nanobubble nucleation. The role of CO2 in the early nucleation of bubble is explained based on the interaction between the bubble and the dissolved CO2 molecules.

The effect of solution chemistry on nucleation of nesquehonite

Several series of nesquehonite nucleation experiments (62 experiments in total) were conducted in aqueous solutions having Mg2+/CO32− activity ratios (here referring to log(aMg2+/aCO32−)) ranging between −0.96 to 2.89, but different saturation states (Ω ranging between 2.49–6.90) and solution pH. The goal was to understand the effect of solution chemistry on the nucleation of nesquehonite. Our experimental results show that induction-time estimates from our precipitation experiments with similar Mg2+/CO32− activity ratios are consistent with classical nucleation theory (CNT), while the surface energy derived from CNT varies with Mg2+/CO32− activity ratios. The induction times of nesquehonite nucleation are scattered noticeably when the saturation state of solution is low (Ω

A Comparison of the Crystallization Inhibition Properties of Bile Salts

Bile salts are natural surfactants present in the human gastrointestinal tract. Therefore, it is essential to consider their effect on the dissolution and crystallization tendency of oral drug formulations. Although a recent study showed that sodium taurocholate delayed nucleation for 11 structurally diverse compounds, there is limited information about the crystallization inhibition properties of other bile salts and whether they are interchangeable in this context. In this study, we evaluated the ability of 13 bile salts to maintain supersaturated aqueous solutions of three compounds: celecoxib, nevirapine, and fibanserin. Most bile salts extended nucleation induction times. However, their inhibitory effects varied depending on the structure and concentration of the bile salt and the drug. The R5 group and hydrophobicity of the bile salt appeared to be essential. Molecular dynamics simulations indicated that van der Waals and hydrogen bonding interactions occurred between nevirapine and bile salts, with...

Gas Nanobubbles as Nucleation Acceleration in the Gas-Hydrate Memory Effect

Gas-hydrate crystals have important roles in various energy and environmental issues and also have potential industrial applications. Yet their formation and dissociation mechanisms remain unclear. To accelerate their crystallization, one can use a thermal hysteresis process called the “memory effect”, which is recognized as a shortening of the induction time of gas hydrate nucleation. Although its mechanism is still under debate, submicron-sized bubbles, called “micro- and nanobubbles (MNBs)”, that are generated after the hydrate dissociation are thought to play an important role. In this study, we use a transmission electron microscope to observe freeze-fracture replicas of the ethane (C2H6)-hydrate dissociated solution to identify the existence of MNBs. We find that a significant number of MNBs remain dispersed in the dissociated solution for more than 1 day. We then measure the induction time of C2H6-hydrate formation under stirred conditions with and without such MNB solutions. Not only in the C2H6-h...

Reliable and Repeatable Evaluation of Kinetic Hydrate Inhibitors Using a Method Based on Crystal Growth Inhibition

Low dosage hydrate inhibitors (LDHIs)—antiagglomerants (AAs) and kinetic hydrate inhibitors (KHIs)—are increasingly used as an alternative to the traditional thermodynamic hydrate inhibitors for controlling gas hydrate problems in the petroleum industry. As nucleation inhibitors, KHIs induce an extended induction time (ti) at particular subcoolings before nucleation of hydrate can proceed to growth. However, due to the stochastic nature of nucleation, gaining repeatable and transferrable induction time results can be very challenging and time-consuming. To overcome this problem, study on KHI crystal growth inhibition (CGI) has yielded a KHI evaluation technique which is considerably simpler than induction time measurements. Moreover, this study shows that KHIs create a number of well-defined hydrate CGI regions as a function of subcooling which are completely repeatable and transferrable between different setups. These regions range from complete inhibition (CIR), to slow growth region (SGR), and ultimate...

Effects of Common Inorganic Salts on Glycine Polymorphic Transformation: An Insight into Salt-Dependent Polymorphic Selectivity

The effects of typical inorganic salts on solution-mediated polymorphic transformation from metastable α-glycine to stable γ-glycine were investigated, with the measurement of induction times of γ-glycine nucleation being the key objective. Interestingly, it was observed that all the inorganic salts examined in this study considerably shorten induction time, showing that they accelerate γ-glycine secondary nucleation to a great extent. Surprisingly, it was found that the divalent cation salts (Ca(NO3)2 and MgSO4) exert a peculiar effect in that they greatly promote γ-glycine secondary nucleation despite their significant inhibition to γ-glycine growth. Furthermore, it was revealed that the monovalent cation salts (NaCl, KNO3, and (NH4)2SO4) enhance γ-glycine nucleation far more than the divalent cation salts. These obtained results provide an insight into the general observation that the polymorphic selectivity of glycine from unseeded solution crystallization is salt-dependent. All the experimental obser...

Mechanistic Design of Chemically Diverse Polymers with Applications in Oral Drug Delivery.

Polymers play a key role in stabilizing amorphous drug formulations, a recent strategy employed to improve solubility and bioavailability of drugs delivered orally. However, the molecular mechanism of stabilization is unclear, therefore, the rational design of new crystallization-inhibiting excipients remains a substantial challenge. This article presents a combined experimental and computational approach to elucidate the molecular features that improve the effectiveness of cellulose polymers as solution crystallization inhibitors, a crucial first step toward their rational design. Polymers with chemically diverse substituents including carboxylic acids, esters, ethers, alcohols, amides, amines, and sulfides were synthesized. Measurements of nucleation induction times of the model drug, telaprevir, show that the only effective polymers contained carboxylate groups in combination with an optimal hydrocarbon chain length. Computational results indicate that polymer conformation as well as solvation free energy are important determinants of effectiveness at inhibiting crystallization and show that simulations are a promising predictive tool in the screening of polymers. This study suggests that polymers need to have an adequate hydrophilicity to promote solvation in an aqueous environment, and sufficient hydrophobic regions to drive interactions with the drug. Particularly, the right balance between key substituent groups and lengths of hydrocarbon side chains is needed to create effective materials.

A kinetic analysis of the transformation from akaganeite to hematite: An in situ time-resolved X-ray diffraction study

The nucleation and growth of akaganeite and its transformation to hematite under hydrothermal conditions were monitored over a temperature range of 80 to 200°C using time-resolved synchrotron X-ray diffraction. In each experiment, akaganeite was the first phase to form and hematite was the final phase. No intermediate phases were identified. The induction time to akaganeite nucleation was ~5525s and 537s at 80°C and 100°C, respectively, yielding an activation energy of 129±15kJ/mol. However, akaganeite nucleated at a constant temperature of 123±5°C when the heater set point was 150°C or higher, suggesting an activation energy for akaganeite nucleation of 0kJ/mol between 150 and 200°C. Hematite nucleation induction times decreased with increasing temperature from 1723s to 110s between 150 and 200°C. Based on a JMAK analysis, the activation energies for the crystal growth and dissolution of akaganeite were 74±8kJ/mol and 125±7kJ/mol, respectively. Our calculated activation energies for hematite nucleation and crystal growth were 80±13kJ/mol and 110±21kJ/mol, respectively.

Investigating the Influence of Polymers on Supersaturated Flufenamic Acid Cocrystal Solutions.

The development of enabling formulations is a key stage when demonstrating the effectiveness of pharmaceutical cocrystals to maximize the oral bioavailability for poorly water soluble drugs. Inhibition of drug crystallization from a supersaturated cocrystal solution through a fundamental understanding of the nucleation and crystal growth is important. In this study, the influence of the three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the flufenamic acid (FFA) crystallization from three different supersaturated solutions of the pure FFA and two cocrystals of FFA-NIC CO and FFA-TP CO has been investigated by measuring nucleation induction times and desupersaturation rates in the presence and absence of seed crystals. It was found that the competition of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and coformer/polymer was a key factor responsible for maintaining supersaturation through nucleation inhibition and crystal growth modification in a cocrystal solution. The supersaturated cocrystal solutions with predissolved PEG demonstrated more effective stabilization in comparison to the pure FFA in the presence of the same polymer. In contrast, neither of the two cocrystal solutions, in the presence of PVP or PVP-VA, exhibited a better performance than the pure FFA with the same predissolved polymer. The study suggests that the selection of a polymeric excipient in a cocrystal formulation should not be solely dependent on the interplay of the parent drug and polymer without considering the coformer effects.

Inhibition–Promotion: Dual Effects of Polyvinylpyrrolidone (PVP) on Structure-II Hydrate Nucleation

Polyvinylpyrrolidone (PVP) is known as a kinetic hydrate inhibitor (KHI) and its inhibiting effect on hydrate nucleation and growth has been widely studied and acknowledged. In this work, the effect of PVP on methane–propane hydrate nucleation was examined in high-pressure autoclave at isothermal conditions. We examined PVP at ultralow concentrations of 50 and 100 ppm to avoid overlapping effects on nucleation and growth and maintain focus on the nucleation stage of the process. Two experimental pressures (Pexp = 6.1 or 9.0 MPa), two cooling rates (2 K/h or 6 K/h), and six subcooling levels (ΔT) ranging from 6.37–10.05 K were applied to induce nucleation. The induction time for hydrate nucleation increased with PVP present at ultralow concentrations, but intriguingly, PVP demonstrated dual effects of inhibition and promotion on hydrate nucleation rate at the experimental pressures examined. The switch from promoting to inhibiting effect on nucleation rate was seemingly not affected by pressure or cooling ...

Studying the Propensity of Compounds to Supersaturate: A Practical and Broadly Applicable Approach

Supersaturating drug delivery systems can enhance the oral bioavailability of poorly soluble drug compounds. Supersaturation of such compounds has been studied in many different ways; however, a more standardized method is required. The rationale of choosing suitable concentrations of supersaturation to study has previously been very inconsistent. This makes comparisons between studies and compounds difficult, as the propensity of compounds to supersaturate varies greatly. This study presents a standardized method to study the supersaturation of drug compounds. The method allows, both, for a ranking of compounds according to their supersaturation propensity and the effectiveness of precipitation inhibitors. The time–concentration profile of supersaturation and precipitation was studied in situ for 4 different concentrations for 6 model compounds (albendazole, aprepitant, danazol, felodipine, fenofibrate, and tadalafil) in the μDISS Profiler™ in fasted-state simulated intestinal fluid. A relation between the induction time of nucleation and the initial supersaturated concentration could be established based on classical nucleation theory. The model compounds had different propensities to upersaturate. The data show that a single degree of supersaturation or concentration would not have described the different systems adequately. The method could be used in early preformulation for characterization of supersaturation propensity of novel compounds or precipitation inhibitor effects.

Model for Interpreting Surface Crystallization Using Quartz Crystal Microbalance: Theory and Experiments.

Surface crystallization of calcium sulfate was investigated using a dissipation crystal quartz microbalance (QCM-D) together with microscopy to understand the mechanical property changes occurring during the growth process. The use of optical microscopy and SEM revealed that needle-shaped crystals grow as clusters on the QCM sensor's surface, not in uniform layers. As crystallization growth progressed, QCM-D revealed inversions between negative and positive frequency shifts. This behavior, a function of the growth of crystals in clusters, is not adequately predicted by existing models. As such, a new mass-to-frequency conversion model is proposed herein to explain the observed frequency inversions. This model is derived from a lumped element approach with point-contact loading and Mason equivalent circuit theory. Critically, the physical phenomena occurring form the basis of the model, particularly addressing the three sources of impedance. When a crystal nucleates and grows, its inertial impedance is considered along with a Kelvin-Voigt link with a hydration layer. A comparison between the proposed model and experimental data, of both frequency and dissipation data for the first four harmonics, shows good agreement for the supersaturations (S = C/C*) of S = 3.75, S = 3.48, and S = 3.22. Additionally, significant improvements over existing models for the case of surface crystallization are observed. The proposed model was therefore able to explain that frequency inversions are caused by a shift from inertia-dominated to elastic-dominated impedance, occurring as a result of crystal growth. Using the nucleation induction time and nucleation rates, determined with imaging, an additional understanding of the crystals' mechanical properties (stiffness and dampening) was obtained.

Non-Photochemical Laser-Induced Nucleation of Sulfathiazole in a Water/Ethanol Mixture

Non-photochemical laser-induced nucleation (NPLIN) is an original and promising nucleation method that has been applied with success to small-molecule organic compounds, proteins, and inorganic compounds, leading to almost 50 publications. After the first application of NPLIN to glycine and carbamazepine, our team has performed NPLIN experiments on sulfathiazole (STZ) for the following reasons: (i) STZ is considered as a model drug for studying polymorphism; (ii) some STZ polymorphs present a two-dimensional packing type, while others have one-dimensional packing; (iii) STZ solubility curves, crystal habits, and crystallization characterization are well documented. First, we have determined the metastable zone limit of STZ in water/ethanol (v/v 1:1) for three temperatures (15, 25, and 40 °C). STZ metastable solutions have been irradiated with a nonfocused nanosecond laser (532 nm) at 25 °C. Nucleation induction time and crystal habits have been compared with those obtained by spontaneous nucleation. Nucle...

Effect of Tween 20 on the Properties of Stearate Oleogels: an in‐Depth Analysis

AbstractThis work deals with the investigation of the polymorphic changes associated with stearic acid in the presence of Tween 20 during the formation of oleogels. Tween 20 was utilized as a crystal habit modifier and its effect on the physical and thermal properties of the oleogels have been studied. Tween 20 was found to stabilize the polymorph B of stearic acid, marked by an increase in the leaf‐like structures. Fluorescent recovery after photobleaching studies suggested Tween 20 concentration‐dependent reduction in the mobile fractions. Gelation studies suggested a delay in the induction time of nucleation of stearic acid in the presence of Tween 20 was due to the decrease in the degree of supercooling. Avrami analysis supported the stabilization of the polymorph B of stearic acid in the presence of Tween 20. XRD measurements indicated that Tween 20 promoted the growth of the stearic acid crystals while forming leaf‐like structures. The molecular rearrangement of the gelator network was quicker and ordered in the Tween 20‐containing oleogels. The increase in ordered arrangement of the stearic acid molecules has lowered the crystal imperfections. In other words, it enhanced the crystal gaps (pores) associated with the gelators. When stress (either thermal or mechanical) was introduced, the strength of the oleogels was decreased due to the syneresis of oil through the pores. An increase in the Tween 20 concentration‐dependent relaxation of the oleogels was also observed due to the polymorphic change and arrangement of the gelators.

Effect of Span 60 on the Microstructure, Crystallization Kinetics, and Mechanical Properties of Stearic Acid Oleogels: An In-Depth Analysis.

Modulation of crystallization of stearic acid and its derivatives is important for tuning the properties of stearate oleogels. The present study delineates the crystallization of stearic acid in stearate oleogels in the presence of Span 60. Microarchitecture analysis revealed that stearic acid crystals in the oleogels changed its shape from plate-like structure to a branched architecture in the presence of Span 60. Consequently, a significant variation in the mobility of the solute molecules inside the oleogel (Fluorescence recovery after photobleaching studies, FRAP analysis) was observed. Thermal analysis (gelation kinetics and DSC) revealed shortening of nucleation induction time and secondary crystallization with an increase in the Span 60 concentration. Furthermore, isosolid diagram suggested better physical stability of the formulations at higher proportions of Span 60. XRD analysis indicated that there was a decrease in the crystal size and the crystallinity of the stearic acid crystals with an increase in Span 60 concentration in the Span 60 containing oleogels. However, crystal growth orientation was unidirectional and found unaltered with Span 60 concentration (Avarmi analysis using DSC data). The mechanical study indicated a composition-dependent variation in the viscoelastic properties (instantaneous [τ1 ], intermediate [τ2 ], and delayed [τ3 ] relaxation times) of the formulations. In conclusion, Span 60 can be used to alter the kinetics of the crystallization, crystal habit and crystal structure of stearic acid. This study provides a number of clues that could be used further for developing oleogel based formulation.