Kinetics Of Polymorphic Transformation Research Articles

A synchrotron X-ray scattering study of the crystallization behavior of mixtures of confectionary triacylglycerides: Effect of chemical composition and shear on polymorphism and kinetics

Cocoa butter equivalents (CBE) are mixtures of triglycerides from multiple sources (e.g., sunflower oil, mango kernel and sal), which resemble cocoa butter (CB) in both physical and chemical properties. Despite being widely used to replace CB in chocolate products, the crystallization behavior of many CBEs is still poorly understood. The aim of this work was to develop a fundamental understanding, at the molecular level, of the crystallization behavior of selected CBEs, and compare it with that of CB. Chromatography was used to determine the composition of CBEs, in terms of fatty acids and triacylglycerides (TAGs), while their thermodynamic behavior and crystallization kinetics were studied using polarized microscopy, differential calorimetry and three different synchrotron X-ray scattering setups. CBEs of different origin and chemical composition (e.g., different ratios of the main CB TAGs, namely POP, SOS and POS) crystallized in different polymorphs and with different kinetics of nucleation, growth and polymorphic transformation. SOS rich CBEs presented showed more polymorphs than CB and POP rich samples; whereas, CBEs with high concentration of POP showed slow kinetic of polymorphic transformation towards the stable β(3L) form.Additionally, it was observed that the presence of small amounts (<1% w/w) of specific TAGs, such as OOO, PPP or SSS, could significantly affect the crystallization behavior of CBEs and CBs in terms of kinetics of polymorphic transformation and number of phases detected (multiple high melting β(2L) polymorphs were identified in all samples studied). Finally, it was found that, regardless of the CBE composition, the presence of shear could promote the formation of stable β polymorphs over metastable β’ and γ forms, and reduced the size of the crystal agglomerates formed due to increased secondary nucleation.

Decoding the role of triacylglycerol composition in the milk fat crystallisation behaviour: A study using buffalo milk fat fractions

The role of triacylglycerols (TAGs) composition in milk fat crystallisation is evaluated from a new perspective by correlating the crystal structures and their predicted TAG contributors. Four different TAG groups, defined by their fatty acid (FA) chain length and saturation are proposed to explain the crystallisation behaviour of different milk fat samples, namely TAGs containing (i) fully saturated long chain FAs, (ii) single unsaturated long-chain FA and (iii) multi unsaturated long-chain FAs, as well as (iv) short-chain FAs. Samples containing different TAGs proportions were obtained from two-step dry fractionation of buffalo milk fat. Liquid chromatography and mass spectrometry (LCMS) was employed to determine the TAGs composition. The crystallisation characteristics were evaluated using small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and polarised light microscopy. The results confirm that fully saturated long chain TAGs are responsible for the formation of high melting point 2L-crystals (d-spacing: 44.1–49.7 Å), whilst the low melting point 3L-crystals (64.4–72.8 Å) are mainly contributed by long chain TAGs containing unsaturated fatty acids. Further, the crystallisation inhibiting effect of asymmetrical TAGs, containing short chain fatty acid (C4-6) is evident. As a final point, effects of the four TAG groups, each given with a specific composition, were examined closely also with respect to their influence on the nucleation and polymorphic transformation kinetics of milk fat crystals.

Thermal stability and polymorphic transformation kinetics in β-MnTe films deposited via radiofrequency magnetron sputtering

A manganese telluride (MnTe) compound is an interesting polymorphic semiconductor with physical properties differing greatly among various polymorphs. In this study, the thermal stability and polymorphic transformation kinetics in β-MnTe films obtained via radiofrequency magnetron sputtering were investigated. The obtained MnTe films with a composition range of 50.5–46.1 at.% Te exhibited a single β phase. The polymorphic transformation temperature from the β (wurtzite-type) to an α (NiAs-type) phase decreased with increasing the Te content. In the non-isothermal analysis using differential scanning calorimetry, the activation energy for β → α transformation was measured to be 1.41 eV, based on Kissinger plots. The retention time of β-MnTe was also investigated via the Ozawa method, and it was estimated to be retained for 4.5 × 109 years at 25 °C. The estimated Avrami exponent of 3.5 indicated that two- and three-dimensional growth at a constant nucleation rate was dominant at the intermediate stage of β → α transformation.

The Unique Crystallization Behavior of Buffalo Milk Fat

A full comprehension of milk fat crystallization is important for the structural development of dairy products such as butter, ice cream, and cheese. The influence of triacylglycerol (TAG) composition on the dynamic of milk fat crystallization and the nanostructure of the formed crystals was investigated using two chemically different types of milk fat, namely buffalo and cow milk fats (BMF; CMF). The TAG composition was determined using liquid chromatography and mass spectrophotometry (LCMS), whereas differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS and WAXS), and polarized light microscopy (PLM) were used to characterize the crystallization behavior of the two milk fats. A total of 37 TAG species were identified in both BMF and CMF, but in different proportions. In particular, BMF was found to have a higher amount of low-molecular-weight TAGs in comparison to CMF. This difference in chemical composition explains the different kinetics of polymorphic transformation in the two samples. Specifically, it clarifies the delay in the nucleation of the β′-polymorph in BMF in comparison to CMF. BMF also showed a higher nucleation rate due to its higher proportion of saturated TAGs and higher melting range. Finally, this work presents a novel interpretation of the mechanism of formation of the β-polymorph (53 A), which has recently become the subject of a vivid debate in milk fat crystallization studies.

Polymorphism and thermophysical properties of l- and dl-menthol

The thermodynamic properties, phase behaviour, and kinetics of polymorphic transformations of racemic (dl-) and enantiopure (l-) menthol were studied using a combination of advanced experimental techniques, including static vapour pressure measurements, adiabatic calorimetry, Tian-Calvet calorimetry, differential scanning calorimetry (DSC), and variable-temperature X-ray powder diffraction. Several concomitant polymorphs (α, β, γ, and δ forms) were observed and studied. A continuous transformation to the stable α form was detected by DSC and monitored in detail using X-ray powder diffraction. A long-term coexistence of the stable crystalline form with the liquid phase was observed. The vapour pressure measurements of both compounds were performed using two static apparatus over a temperature range from 274 K to 363 K. Condensed-phase heat capacities were measured by adiabatic and Tian-Calvet calorimetry in the wide temperature interval from 5 K to 368 K. Experimental data of l- and dl-menthol are compared mutually as well as with available literature results. The thermodynamic functions of crystalline and liquid l-menthol between 0 K and 370 K were calculated from the calorimetric results. The thermodynamic properties in the ideal-gas state were obtained by combining statistical thermodynamics and quantum chemical calculations based on a thorough conformational analysis. Calculated ideal-gas heat capacities and experimental data on vapour pressure and condensed-phase heat capacity were treated simultaneously to obtain a consistent thermodynamic description. Based on the obtained results, the phase diagrams of l-menthol and dl-menthol were suggested.

Predicting kinetics of polymorphic transformations from structure mapping and coordination analysis

To extend rational materials design and discovery into the space of metastable polymorphs, rapid and reliable assessment of their lifetimes is essential. Motivated by the early work of Buerger (1951), here we investigate the routes to predict kinetics of polymorphic transformations using solely crystallographic arguments. As part of this investigation we developed a general algorithm to map crystal structures onto each other and construct transformation pathways between them. The developed algorithm reproduces reliably known transformation pathways and reveals the critical role that the dissociation of chemical bonds along the pathway plays in choosing the best (low-energy barrier) mapping. By utilizing our structure-mapping algorithm we were able to quantitatively demonstrate the intuitive expectation that the minimal dissociation of chemical bonds along the pathway, or in ionic systems, the condition of coordination of atoms along the pathway not decreasing below the coordination in the end compounds, represents the requirement for fast transformation kinetics. We also demonstrate the effectiveness of the structure-mapping algorithm in combination with the coordination analysis in studying transformations between polymorphs for which a detailed atomic-level picture is presently elusive.

Quantification of gabapentin polymorphs in gabapentin/excipient mixtures using solid state 13C NMR spectroscopy and X-ray powder diffraction

Gabapentin was used as a model pharmaceutical compound with susceptibility to polymorphic transformation as a function of environmental and mechanical stress. The utility of 13C CP/MAS NMR and XRPD as stability-indicating methods to quantify polymorphic transformation kinetics was investigated. Polymorphic Form II and III were distinguishable based on their chemical shift and distinct diffraction peak differences. Reproducible and accurate quantification of polymorphic composition in the presence of selected excipients was demonstrated using both signals from 13C CP/MAS NMR spectra and XRPD patterns. The effect of excipients on polymorphic transformations (Form II→III) was determined by measuring the transformation after co-milling. Both 13C CP/MAS NMR and XRPD were capable of measuring polymorphic composition in co-milled excipient mixtures without excipient peak interference. The amounts of Form III present in co-milled mixtures containing colloidal silicon dioxide, starch, hydroxy propyl cellulose and dibasic calcium phosphate were 8.7, 21, 33, and 39mol%, respectively. A quenching procedure for obtaining 13C CP/MAS NMR spectra and environmentally-controlled XRPD were devised to determine polymorphic transformation kinetics of co-milled excipient mixtures during storage.

Miniaturized X-ray powder diffraction assay (MixRay) for quantitative kinetic analysis of solvent-mediated phase transformations in pharmaceutics

Many pharmaceutical compounds exhibit polymorphism, which may result in solvent-mediated phase transformations. Since the polymorphic form has an essential influence on physicochemical characteristics such as solubility or dissolution rate, it is crucial to know the exact polymorphic composition of a drug throughout pharmaceutical development. This study addressed the need to perform quantitative X-ray analysis of polymorphic mixtures on a 96-well scale (MixRay). A calibration of polymorphic mixtures (anhydrate and hydrate) was performed with three model drugs, caffeine, piroxicam, and testosterone, and linear correlations were obtained for all compounds. The MixRay approach for piroxicam was applied to a solubility and residual solid screening assay (SORESOS) to quantify the amount of hydrate and anhydrate corresponding to kinetic bulk concentrations. Changes in these drug concentrations correlated well with the kinetic changes in the residual solid. The influence of excipients on the solid state and kinetic concentrations of piroxicam was also studied. Excipients strongly affected polymorphic transformation kinetics of piroxicam and concentrations after 24h depended on the excipient used. The new calibration X-ray method combined with bulk concentration analysis provides a valuable tool for both pharmaceutical profiling and early formulation development.

Morphology and kinetics of polymorphic transformations in K0.965Rb0.035NO3 single crystals

Polymorphic transformations in K0.965Rb0.035NO3 single crystals have been investigated by optical microscopy and X-ray diffraction. The equilibrium temperature between modifications II and III of the crystal studied is determined to be T = 452 ± 0.5 K. It is found that polymorphic transformations are of the single crystal ↔ single crystal type and occur with the formation and growth of nuclei of new crystals in matrix ones at II ↔ III transformations. An empirical dependence of the growth rate of modification III on temperature is established in the form ϑ = ϑ = (–0.478ΔT + 0.712ΔT2–0.00041ΔT3) × 10–2 cm/s (ΔT = Ttr–T0, where Ttr is the transformation temperature and T0 is the equilibrium temperature).

Tailoring crystal shape and polymorphism using combinations of solvents and a structurally related additive

Controlling polymorphism is one of the most difficult challenges for the pharmaceutical industry. Polymorphs of the same compound can have very different properties that might affect the quality of the final drug. Many studies have focused on trying to determine robust methods to produce specific polymorphs that exhibit the desired characteristics of the drug (solubility and rate of dissolution in particular). The choice of solvent, pH, kinetic conditions and the presence of impurities can all have very strong effects on the polymorphic outcome of cooling crystallization. In this work, the crystallization of ortho-aminobenzoic acid (OABA) in the presence of a structurally related additive (benzoic acid) will be studied using both in situ PAT tools and offline techniques. The effect on morphology, polymorphic outcome, polymorphic transformation kinetics and tendency towards agglomeration in different solvents will be studied using a large variety of instrumentation. The incorporation of benzoic acid in solid solution in the three different polymorphs of OABA will also be quantified and discussed. The results of the crystallization experiments and offline analysis will be compared and interpreted using the information on the crystal structures of the three OABA polymorphs from the Cambridge Crystallographic database.

Kinetics of the polymorphic phase transformation of Cu6Sn5

Cu6Sn5 is a critical intermetallic compound in soldering and three-dimensional integrated circuit packaging technology and exists in at least five different crystal structures in the solid state, with a polymorphic phase transformation from hexagonal to monoclinic structures occurring on cooling. The kinetics of polymorphic transformations in Sn-rich Cu6Sn5 and Cu-rich Cu6Sn5 is systematically investigated in this study. This includes the generation of continuous cooling transformation diagrams as well as time–temperature transformation diagrams. Techniques used include variable temperature synchrotron powder X-ray diffraction and differential scanning calorimetry. The findings have important implications for the manufacture of solder joints and their in-service performance.

Improvement of weldability and evaluation criteria for high-strength pipe steel heat-affected zone reliability

Criteria are formulated for evaluating weldability on the basis of methods simulating welding thermal cycles and analysis of austenite polymorphic transformation kinetics in the thermally affected zone. Results are provided for evaluating the joint heat-affected zone (HAZ) cold resistance under the influence of thermal action during welding of thick-walled pipes for considerable heat input and the tendency for cold cracks during welding with small heat input. The effect of alloying elements, i.e., nickel and chromium, and also vanadium and molybdenum in steels microalloyed with niobium on ductile-brittle failure parameters during impact testing is demonstrated. Microalloying niobium-containing steels with vanadium and molybdenum leads to HAZ metal embrittlement. Optimum cooling rates after welding are determined with which HAZ metal cold resistance at down to –30°C is provided are determined.

Polymorphic and kinetic investigation of adefovir dipivoxil during phase transformation

To search polymorphs of adefovir dipivoxil (AD), the polymorphic transformation approach in solution was developed. Also, the kinetics of polymorphic transformation was investigated to effectively control polymorphs. The AD crystals were obtained by crystallization at −10 °C, and then the polymorphic transformation was induced by raising temperature. The polymorphs of AD were confirmed using DSC, XRD and solubility analyses. The polymorphic fraction during transformation was monitored for kinetic investigation. Via polymorphic transformation in solution, four polymorphs of AD were found and two of them were new (NF-I, NF-II). The DSC analysis revealed that solvate form (NF-I) was changed to form-V in solid state, and then re-crystallized to NF-II at 93 °C, and finally became form-I at 97 °C. This serial change of polymorphs in DSC was identical to polymorphic transformation sequence in solution. The kinetic rates of polymorphic transformation described by nucleation and mass transfer theories were well matched with experimental measurement. The polymorphic transformation approach was effective to search polymorphs of which the structure was changed to the other one in the solution. The kinetic information of polymorphic transformation predicted by Volmer's nucleation model and Stokes–Einstein diffusion equation was valuable for exact control of polymorphic purity.

On the role of oxygen vacancies and lattice strain in the tetragonal to monoclinic transformation in alumina/zirconia composites and improved environmental stability

The aim of this paper is to clarify at the nanometer scale the relevant factors influencing the hydrothermal resistance to polymorphic transformation of alumina/zirconia composites, primary candidates for artificial joint applications. The topographic distribution of oxygen vacancies and lattice strain on the composite surface were visualized by means of cathodoluminescence spectroscopy and mapped as a function of exposure time in a thermally activated water vapor environment (i.e., simulating the exposure in human body). Systematically monitoring the optical activity of oxygen vacancies in both alumina and zirconia phases also revealed the effect of surface lattice strain accumulation on the kinetics of polymorphic transformation. From the presented data, an explicit role is evinced for surface oxygen vacancy formation in the alumina matrix, an important step in the complex cascade of mechanochemical events determining the superior environmental resistance of the composite.

Kinetics of polymorphic transformation in ferrite-pearlite steel on heating in the intercritical temperature range

However, the processes in structural steel on heating in the intercritical range and their influence on the structure and properties of the metal have not been adequately studied. Taking account of the scientific and practical interest in polymorphic transformation within the intercritical temperature range, it is appropriate to study the transformations in ferrite‐pearlite steel (considered in the present work) and in high-strength steel and to determine the physicomechanical properties of the rolled steel. In the first stage of this work, attention focuses on carbon and low-alloy sheet steel: eU 3 OO , 09 E 2 e , 09 E 2 aiA , and 16 E 2 Ai steel (Tables 1 and 2). We know that the position of the intercritical range and the transformations within it depend not only on the chemical composition of the steel but also on its initial structure and heating conditions [5‐12]. For steel subjected to mechanical or phase hardening, at high heating rates, the critical points A c 1 and A c 3 lie lower than for steel with equilibrium structure. With slower heating, facilitating recovery and recrystallization, the critical points are higher. Therefore, to obtain more general results, the steel is investigated in two structural states: after annealing (heating to 920 ° C, holding for 20 min, cooling in the furnace to 300 ° C and then in air); and after phase hardening (quenching in water from 920 ° C after 20-min holding at 920 ° C). The thickness of the plate samples is equal to the sheet thickness, with a width of 200 mm and a length of 300 mm. The position of the critical points A c 1 and A c 3 and the relative volume of α γ transformation in heat-treatment conditions or in the thermal cycles of welding may be determined by means of a high-speed vacuum dilatometer, for example [13]; however, this method is slow. Therefore, a different dilatometer design is proposed: the rod samples are electrically heated in air, and oxidation and scale formation are eliminated by applying a metallicchrome layer of thickness 4‐8 µ m. To equalize the temperature over the sample length, a working section of stepped form is employed (Fig. 1). Thermal changes in

Preparation of Glyceroglycolipids from Pumpkin and Their Effects on Polymorphic Transformation of Cocoa Butter.

Monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and trigalactosyldiacylglycerol (TGDG) were extracted from pumpkin, then hydrolyzed to the corresponding galactosylmonoacylglycerols by 1, 3-specific lipase from Rhizopus arrhizus; MGDG was then hydrolyzed to diacylglycerol (DG) by β-galactosidase from Aspergillus oryzae. The kinetics of polymorphic transformation on cocoa butter and the effect caused by the addition of these seven glyceroglycolipids were investigated. Each glyceroglycolipid could be incorporated at the level of 5% into the cocoa butter without changing the crystal lattice. The polymorphic transformation on cocoa butter was induced by continuous temperature cycling between 32 and 20°C at 12 h intervals and monitored with a differential scanning calorimeter. The result indicated that MGDG, DGDG, TGDG and DG significantly retarded the polymorphic transformation from Form V to VI of cocoa butter compared to the control, while the other glyceroglycolipids had no effect. The addition of MGDG was the most effective. These results indicate that the number of the acyl chain and galactose of glyceroglycolipid strongly influence the polymorphic transformation of cocoa butter.

Effects of Glyceroglycolipids Prepared from Various Natural Materials on Polymorphic Transformation of Cocoa Butter.

Monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and trigalactosyldiacylglycerol (TGDG) were prepared from various natural materials. In all glyceroglycolipids, linoleic acid, linolenic acid, palmitic acid, oleic acid and stearic acid were the major components. The kinetics of polymorphic transformation on cocoa butter and the effect caused by the presence of the glyceroglycolipids prepared from carrot, corn, wheat flour and Chlorella pyrenoidosa were investigated. Each glyceroglycolipid can be incorporated at the level of 5% within the cocoa butter without changing the crystal lattice. The polymorphic transformation on cocoa butter was induced by continuous temperature cycling between 32 and 20°C at 12 h intervals and monitored with a differential scanning calorimeter. The test results indicated that MGDG and DGDG significantly retarded the polymorphic transformation from Form V to VI on cocoa butter compared with the control, with the addition of MGDG being the most effective. These results indicate that MGDG and DGDG extracted from various natural materials are effective in retarding the polymorphic transformation of cocoa butter.

Effect of binders on polymorphic transformation kinetics of carbamazepine in aqueous solution

The effects of binders on the polymorphic transformation kinetics of carbamazepine (CBZ) were investigated by thermal analysis and X-ray diffraction analysis. The binders used were hydroxypropylcellulose (HPC) (HPC-SL, molecular weight 30 000–50 000; HPC-M, molecular weight 50 000–70 000; HPC-L, molecular weight 110 000–150 000). CBZ anhydrate form I and various concentrations of binder solutions were mixed at 1000 rpm and 25°C. The amount of dihydrate transformed was evaluated based on the latent heat due to dehydration on DSC curves. Since the first-order plots for transformation process of CBZ showed a straight line, the transformation rate constant, k and induction period, IP were estimated based on first-order kinetics by the least-squares method. The k of CBZ decreased with increase of HPC-L concentration, but the IP increased. In contrast, the k of phase transformation on addition of crystal seeds was almost the same as that without seeds, but the IP significantly decreased on seed addition. The result suggested that IP was a nucleus formation process, but the seed addition did not affect the crystal growth process. The molecular weight effect of HPC on the transformation suggested that the k of HPC-SL was the largest, with the rank order being HPC-SL>HPC-M>HPC-L. The order for IP was HPC-L>HPC-SL>HPC-M. The relation between IP and kinematic viscosity had a straight line, but the k decreased with increase of kinematic viscosity. The increase of IP on addition of HPC might be induced by inhibition of the formation of nuclei by the steric intermolecular effect of HPC and decrease of Δ μ. Therefore, HPC strongly inhibited nucleus formation in the crystallization of CBZ.

Application of thermal analysis (DSC) in the study of polymorphic transformations

The effects of chemical structure and composition on phase transitions in triglycerides are reviewed. The presence of surfactants may help to better discern between the polymorphic behaviour of isomorphous triglycerides. The effect of different surfactants depends on their hydrophilic group and on the thermal properties of the triglyceride. The mechanism of the effects on the polymorphic transitions in triglycerides 18 interpreted considering the different modes of their transformations either through solid/melt/solid or through solid/solid. The DSC technique used was effective in estimating the extent and the mechanism of transformations. The thermal history and rate of scanning affect strongly the kinetics of polymorphic transformations.

Dynamic control of polymorphic transformation in triglycerides by surfactants: The button syndrome

AbstractThe kinetics of polymorphic transformations in monoacid saturated triglycerides and the influence caused by the presence of certain solid surfactants were investigated. Selected emulsifiers can be incorporated at the level of 10 wt% within the triglyceride, without changing the crystal lattice; on the other hand, their presence affects the heat capacity of the triglyceride and the NMR relaxation time T1. Following the polymorphic transformation both during aging and during heating in the DSC, it was observed that both the mechanism and rate of transformation of the triglyceride strongly depend on the kinetic conditions and on its own chemical structure. In conjunction with these results it also was observed that the effect of the emulsifier is strongly dependent on the transformation conditions. The kinetic effect of the additive on the solid‐solid transformation has been found to be strictly associated with its hydrophilic moiety structure; a model of molecular incorporation has been proposed which describes the arrangement of the surfactant molecules parallel to the triglyceride chains and formation of vacancies. The selectivity of the additive concerning its effect of dynamic controller of polymorphic transformations has been explained by its capacity to create hydrogen bonds with the neighboring triglycerides, which was called the “Button Syndrome.” The wide range of different additives and triglycerides used supplied a better understanding of the factors which determine the polymorphic and crystallization behavior in triglycerides.