Investigation of the Crystallization of Disodium 5′-Inosinate in a Water + Ethanol System: Solubility, Nucleation Mechanism, and Crystal Morphology

In this work, the solubility of IMP in a water + ethanol system was measured by a gravimetric method at the temperature range from 283.15 to 323.15 K. To explain the solubility behavior of IMP in this system, a model was applied to quantitatively describe the effect of dielectric constants on the solubility of IMP. Then, the induction time was determined to be related to the supersaturation level for analysis of the nucleation mechanism, indicating that homogeneous nucleation dominated the nucleation process at higher supersaturation, while heterogeneous nucleation was more important mechanism at lower supersaturation. Finally, the molecular modeling was carried out to understand the effect of supersaturation on the crystal habits of IMP: the rodlike products preferred to form at high supersaturation, while flakelike products formed at low supersaturation, as shown in the microscopy images. In summary, supersaturation should be considered in the process of optimizing IMP crystallization operation conditions

Wet milling, seeding, and ultrasound in the optimization of the oiling-out crystallization process

Complicated solution environments in oiling-out crystallization can lead to particle agglomeration with large size distribution and low purity of the products, due to complex interactions among two liquid phases and one solid phase during the oiling out crystallization. This research mainly focuses on optimization of size distribution by control particle agglomeration during the oiling-out crystallization process in model system of propyl paraben-ethanol-water. Nucleation-control technologies, wet milling, seeding and ultrasound were investigated to limit the agglomeration. Further investigations of wet milling was applied before the nucleation or in the crystal growth process with different geometries, such as the coarse, medium and fine rotor-stator tooth pairs. An integrated process analytical technology tools (PAT) array, including focused beam reflectance measurement (FBRM), particle visual monitoring(PVM), 2 and attenuated total reflectance ultraviolet/visible(ATR-UV/vis), was used to observe the droplet formation of the dispersed phase, size distributions, particle shapes during the nucleation and crystal growth. The results demonstrate that wet milling, seeding and ultrasound technologies can help to the control of the particle size distribution in the complex solution environments with different levels of efficiencie

Correlation of Solubilities of Hydrophilic Pharmaceuticals versus Dielectric Constants of Binary Solvents

In this paper, the polarity of binary solvents was studied by the sum law of cube roots of the dielectric constant. During the antisolvent crystallization process, the composition of the binary solvents and their dielectric constants changed simultaneously. These results demonstrated that variation of the solubility is dependent on the polarity of the binary solvents. On the basis of experiments, a new model was put forward to quantitatively describe the relationship between the solubility of hydrophilic pharmaceuticals and the dielectric constants of the binary solvents. Furthermore, this model was tested and verified by solubility data of other pharmaceuticals published in the literature with high accuracy

Temperature-Responsive Cocrystal Engineering for Efficacious Delivery of Poorly Water-Soluble Herbicide

Addressing the challenges posed by the low water solubility of numerous herbicides is crucial as it directly affects their bioavailability and efficacy. This limited solubility often results in overapplication, increasing both environmental persistence and risks to human health and aquatic ecosystems. Atrazine (ATR), a widely recognized photosynthesis inhibitor, is emblematic of this dilemma, often requiring doses that far exceed the optimal levels for effective weed control. Cocrystal engineering has emerged as a promising solution. In our study, we synthesized cocrystals of ATR with propanedioic acid (PA) and succinic acid (SA). These cocrystals displayed a marked enhancement in intrinsic dissolution rates, with increases up to most 22.518-fold across a temperature range of 10–30 °C, which in turn greatly improved ATR’s release dynamics. In addition, the solubility varied, increasing to different degrees at different temperatures. This augmentation not only elevated its herbicidal potency, evident from the preferential order of ATR-PA over ATR-SA and then ATR, but also safeguarded against any negative impacts on crop corn. Intriguingly, an increment of just 10 °C in temperature had a more pronounced effect than doubling the herbicide dosage, highlighting the pivotal role of ambient conditions. Overall, our findings highlight the potential of cocrystal engineering to optimize the performance and mitigate the environmental impact of herbicides with restricted water solubility

Investigation of agglomeration in the presence of oiling out in the antisolvent crystallization process

Oiling out during the crystallization process often generates agglomeration. This research is focused on the control of agglomeration in the antisolvent crystallization of the propylparaben-ethanol-water system in the presence of oiling out, that is, the liquid-liquid phase separation phenomenon. Crystallization trajectories were designed to start from a homogeneous solution with different initial concentrations of propylparaben in ethanol, crossing the liquid-liquid phase separation region in the ternary phase diagram by adding the antisolvent of water. A combination of process analytical technology tools, such as focused beam reflectance measurement, particle visual monitoring, and attenuated total reflectance ultraviolet/visible, enabled the detection of the different stages of the oiling out crystallization process, including the droplet formation of the dispersed phase, prenucleation, nucleation, and crystal growth both in the liquid-liquid phase-separated system and in the homogeneous solution. The crystals tended to form normally at higher initial concentrations of propylparaben while tending to agglomerate at a lower initial concentration. Crystallization experiments were also performed with the addition of sonication, with variation in sonication start time, duration, and power. The results showed that ultrasound could reduce the agglomeration dependent on the initial application time. The mechanism of crystallization and agglomeration in oiling out was discussed

Insight into the Role of Hydrogen Bonding in the Molecular Self-Assembly Process of Sulfamethazine Solvates

The new solid forms screening of sulfamethazine was conducted in 16 kinds of different pure solvents. Four new sulfamethazine solvates were reported for the first time, and three crystal structures of solvates were successfully determined from single-crystal X-ray diffraction data. The results showed that sulfamethazine solvate formation directly depended on the solvents used in the experiments. The solvent properties were used to evaluate the effects of solvent on solvate formation. It was found that the H-bond acceptor ability of the solvent was the main factor that governed the solvate formation. The H-bonded motifs in the structures of solvates have been fully characterized. The results revealed that sulfamethazine solvate formation was mainly driven by molecular self-assembly through hydrogen bonding between solvent and solute molecules. Meanwhile, the crystal structures results also showed that the sulfamethazine molecule had flexible conformation. Furthermore, the principles of different sulfamethazine molecules packing in different crystal structures were discussed from the view of molecular intermolecular interactions and the molecular conformation

Solubility and Thermodynamic Stability of the Enantiotropic Polymorphs of 2,3,5-Trimethyl-1,4-diacetoxybenzene

The solubility data of two polymorphs of 2,3,5-trimethyl-1,4-diacetoxybenzene (TMHQ-DA) in ethanol, 1-propanol, 2-propanol, and 1-butanol at various temperatures were experimentally measured using gravimetrical method and correlated by the modified Apelblat model and the van’t Hoff equation, respectively. Differential scanning calorimetry (DSC) and thermogravimetry (TG) analyses were performed to investigate the thermodynamic stability and the transition of the two forms of TMHQ-DA. An enantiotropic relationship was found between TMHQ-DA Form A and TMHQ-DA Form B, and the transition point between them was experimentally determined to be 314.50 ± 1 K. A thermodynamic model for estimation of the transition point was also derived, and the estimated results are satisfactorily consistent with the experimental values. Finally, the accuracy of the transition point obtained in this research was validated by the polymorphic transformation experiments monitored using Raman spectroscopy

Flexible Optical Waveguides in Heterocyclic Schiff Base Self-Assembled Hydrogen-Bonded Solvates

Flexible fluorescent crystalline materials exhibit both mechanical and optical properties and have received great attention due to their potential applications in flexible optical devices. Simultaneously adjusting the mechanical and optical properties of crystalline materials remains interesting and challenging. In the present work, a guest molecule was introduced via hydrogen-bonded solvation, which achieved excellent mechanical elasticity and higher fluorescence emission than that of the host heterocyclic Schiff base molecule crystal itself. The crystal structure–property relationship and the molecular mechanism of the elasticity were then investigated in detail. It revealed that solvent molecules play a key role in changing both the stacking of fluorescent molecules and the interaction energy framework. In addition, the flexible fluorescent solvate exhibits a good waveguide property. A bent crystal was found to have a larger optical loss coefficient than a straight crystal. Furthermore, the size effect on the optical loss coefficient of the waveguide was discussed in which the optical loss coefficient decreases as the sizes increase. Such a size effect is usually neglected in waveguide material research and should be complemented in the performance evaluation of optical waveguides

Flexible Optical Waveguides in Heterocyclic Schiff Base Self-Assembled Hydrogen-Bonded Solvates

Flexible fluorescent crystalline materials exhibit both mechanical and optical properties and have received great attention due to their potential applications in flexible optical devices. Simultaneously adjusting the mechanical and optical properties of crystalline materials remains interesting and challenging. In the present work, a guest molecule was introduced via hydrogen-bonded solvation, which achieved excellent mechanical elasticity and higher fluorescence emission than that of the host heterocyclic Schiff base molecule crystal itself. The crystal structure–property relationship and the molecular mechanism of the elasticity were then investigated in detail. It revealed that solvent molecules play a key role in changing both the stacking of fluorescent molecules and the interaction energy framework. In addition, the flexible fluorescent solvate exhibits a good waveguide property. A bent crystal was found to have a larger optical loss coefficient than a straight crystal. Furthermore, the size effect on the optical loss coefficient of the waveguide was discussed in which the optical loss coefficient decreases as the sizes increase. Such a size effect is usually neglected in waveguide material research and should be complemented in the performance evaluation of optical waveguides

Thermodynamic Properties of Polymorphs of 2,2′-Thiodiethylene Bis[3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)propionate]

In this work, two polymorphic forms of 2,2′-thiodiethylene bis­[3-(3,5-di<i>tert</i>-butyl-4-hydroxyphenyl)­propionate] (abbreviated as TBHP) were successfully isolated, identified, and characterized by using powder X-ray diffraction and differential scanning calorimetry. It was found that form I has a lower melting temperature than form II. The solubility data of both form I and form II of TBHP in six pure solvents were experimentally measured in the temperature range of (283.15 to 318.15) K at atmospheric pressure by using a dynamic method. For all of the tested solvents, the solubility data of TBHP form I are higher than those of form II. The modified Apelblat equation was used to correlate the solubility of TBHP form I and form II. The mixing Gibbs energy, the mixing enthalpy, and the mixing entropy of both forms were also determined. It was also found that mixing processes of both forms are endothermic, entropy-driven, and spontaneous. Combining the DCS data and all of the thermodynamic data, it was concluded that the relationship between form I and form II of TBHP is monotropic