Non-monotonic metastable zone-width behavior in cooling cocrystallization: a case study on the sulfamethazine-acetylsalicylic acid cocrystal system

Effects of three different organic acids including racemic malic acid, succinic acid, and citric acid, which act as an impurity on the solubility and metastable zone width of zinc lactate (ZnL2), have been studied. The results show that the presence of all examined impurities increases the solution solubility and the values of solubility increase with increasing impurity concentration. The introduction of impurity also leads to a reduction on the metastable zone width, and the reductions are pronounced when the impurity concentration increased. Further, experimental data of metastable zone width were analyzed using the expression of the Nývlt’s approach and self-consistent Nývlt-like approach, which can be expressed in the form: ln(ΔTmax/T0) = Φ + β ln b, with intercept Φ = {(1 – m)/m}ln(ΔHd/RTlim) + (1/m)ln(f/KT0) and slope β = 1/m. Here T0 and Tlim are the saturation and nucleation temperature, respectively. m is the apparent nucleation order, and K is a new nucleation constant related to the factor f defined as the number of stable nuclei per unit volume, ΔHd, the heat of dissolution and R the gas constant. Comparing to the former one, the latter approach provides a more satisfactory estimation for the metastable zone width at varying saturation temperature T0. The constant β for specific system reveals independence of the temperature, while the constant Φ increases with increasing saturation temperature. In addition, both constants are proportional to the impurity concentration. Crystal habits of final products are also influenced in the presence of impurities, but the crystal structures are barely changed.

A new view on the metastable zone width during cooling crystallization

The role of growth environment on the crystallization of normal alkanes in the homologous series from C18H38 to C29H60

Determination of the metastable zone width and induction period of urea phosphate. The effects of saturation temperature, cooling rate, stirring rate, and impurity ions on the width of metastable region of urea phosphate crystals and the effect of supersaturation on its induction period were studied. The results show that the width of the crystallization metastable zone narrows with the increase of the saturation temperature, the stirring rate, and the decrease of the cooling rate. The apparent nucleation series m is calculated to be 1.021. The crystallization induction period becomes shorter as the increasing supersaturation S. Impurity ions increase the width of the metastable zone of phosphoric acid. F- has the most significant effect on the width of the metastable zone, and the effect of SO42- is relatively weakest.

Nucleation kinetics from metastable zone widths for sonocrystallization of l-phenylalanine

A study of metastable zone width (MSZW) and nucleation parameters for a cooling crystallization of DL-malic acid-water system is described in this paper. Experimental determination of the MSZW was performed using a laser method in order to carry out the estimation of nucleation parameters. Measured MSZWs can be affected by a variety of parameters, such as cooling rate, saturation temperature, agitation rate, and so on. In this work, the MSZWs were found to decrease with an increase of saturation temperature, and levels of agitation, while it increased with an increase of cooling rate. Two classical theoretical approaches, Nyvlt’s approach and self-consistent Nyvlt-like approach were used to analyze the experimental data on MSZWs.

Determination of metastable zone width of potassium sulfate in aqueous solution by ultrasonic sensor and FBRM

The metastable zone width (MSZW) of SrCl2·6H2O during cooling crystallization was determined by the focused beam reflectance measurement (FBRM). The effects of the saturation temperature, cooling rate, stirring rate, and Ca2+ ion impurity on the MSZW were investigated. The MSZW increased with the increase in the cooling rate and decreased with the increase in the saturation temperature, stirring rate, and Ca2+ ion concentration. Moreover, the effect of seed crystals on the MSZW was investigated, where two types of seeds were used, namely, seed 1# and 2# with volume mean crystal sizes of 64 and 218 µm, respectively. The seeded MSZW decreased than the unseeded one. The MSZW of seed 1# was greater than that of seed 2# when the same amount of seed was used. The MSZW of seed 1# increased with the increase in the seed loading, whereas that of seed 2# decreased.

The saturation curve, metastable zone width (MSZW) and primary nucleation kinetics were measured and estimated during sodium sulfate cooling crystallization process. The MSZW is commonly used to characterize crystal nucleation and determine the operation window for crystallization process. The MSZW is the difference between the saturation temperature and the temperature at which crystals are formed at different temperatures, cooling rates and agitating rates. The approach to interpret the MSZW obtained by polythermal method using the classical nucleation theory by Nyvlt was extended. Interfacial energy was determined for the growth of sodium sulfate crystals. Nucleation parameters such as surface entropy factor, radius of critical nucleus, Gibbs free energy, and critical energy barrier were investigated. The nucleation order was established based on the measurements of MSZW dependence on cooling rate and agitating rate. It was experimentally observed that there is rise of solubility with increase of temperature. When the temperature becomes higher, solubility gradually declines. In this investigation, MSZW was observed to enhance with increase of cooling rate and decrease with increase of agitating rate.

The metastable zone for a nylon 12‐toluene solution was determined in an established constant cooling rate apparatus. Supersaturation solubility curves and the equilibrium solubility curve are unparallel one to another. The metastable zone width under seeded conditions is dependent on the cooling rate, the retention time and the saturation temperature. And the metastable zone width under unseeded conditions is dependent on the cooling rate, the agitation rate and the saturation temperature. Through constant cooling rate crystallization experiments, two empirical correlations pertaining to the metastable zone of the solution have been found.

The metastable zone width (MSZW) of p-methoxybenzoic acid (PMBA) in an ethanol-water system was measured using the polythermal method. The nucleation order m obtained by the Nývlt’s model indicates the nucleation of PMBA following a progressive nucleation mechanism at low saturation temperature (m = 3.18–7.50) and an instantaneous nucleation mechanism at high saturation temperature (m = 1.46–2.55). Then, combined with the metastable zone experiment and the Sangwal model, we found that the MSZW and the interfacial energy reached the maximum when the mass fraction of ethanol was 0.8, which resulted in the smallest crystal product size. Meanwhile, the maximum and obtained based on the modified Sangwal model indicating the PMBA needs to overcome a higher nucleation barrier in the ethanol mass fraction of 0.8. Finally, we proposed a preferential strategy for adjusting MSZW by correlating the interfacial energy with the change in ethanol mass fraction, saturation temperature, and cooling rate, respectively.

Study on the nucleation kinetics of DL-methionine based on the metastable zone width of unseeded batch crystallization

Influence of reaction parameters on oxalic acid crystallization using conventional and ultrasonication: Doehlert matrix

Determination of metastable zone width and nucleation kinetics for combined cooling and antisolvent crystallization of L-asparagine monohydrate in water-isopropanol mixture

The metastable zone widths (MZWs) of triethanolamine hydrochloride ([HTEA]Cl), defined as the maximum temperature difference Delta T(max) a solution can withstand before crystallization of a solid phase, in water, ethanol-water, and HCl-water mixed solvents have been determined at a saturation temperature T(0) range from 293.15 to 303.15 K with cooling rate R from 3 to 8 K.h(-1). Solubilities of [HTEA]Cl in ethanol water mixtures have also been obtained using a dynamic method. An equation of MZW with similar form to Sangwal's equation was derived from the fundamental driving force of crystallization based on chemical potential. With the newly obtained equation, the experimental values of MZW Delta T(max) for [HTEA]Cl-water system at 298.15 K was correlated with the cooling rate R by ln(Delta T(max)/T(0)) = -6.140 + 1.222 ln R. The enthalpy of mixing Delta H(mix) was calculated with the solubility data, and the result of differential scanning calorimetry (DSC). For [HTEA]Cl-water system, the value of -Delta H(mix) was determined to be 30.88 kJ.mol(-1), and the addition of both HCl and ethanol led to a decrease of -Delta H(mix). The experimental results also showed that MZW could be greatly enhanced when ethanol and HCl were added. It was found that the values of MZW decrease with -Delta H(mix) for both [HTEA]Cl-ethanol-water and [HTEA]Cl-HCl-water systems at the same saturation temperature and cooling rate.