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This study aimed to address the issue of the low solubility in the model drug probenecid (PRO) and its impact on bioavailability. Two salts of probenecid (PRO), 4-aminopyridine (4AMP), and 4-dimethylaminopyridine (4DAP) were synthesized and characterized by PXRD, DSC, TGA, FTIR, and SEM. The crystal structures of the two salts were determined by SCXRD, demonstrating that the two salts exhibited different hydrogen bond networks, stacking modes, and molecular conformations of PRO. The solubility of PRO and its salts in a phosphate-buffered solution (pH = 6.8) at 37 °C was determined, the results showed that the solubility of PRO salts increased to 142.83 and 7.75 times of the raw drug, respectively. Accelerated stability experiments (40 °C, 75% RH) showed that the salts had good phase stability over 8 weeks. Subsequently, Hirshfeld surface (HS), atom in molecules (AIM), and independent gradient model (IGM) were employed for the assessment of intermolecular interactions. The analyses of salt-forming sites and principles were conducted using molecular electrostatic potential surfaces (MEPs) and pKa rules. The lattice energy (EL) and hydration-free energy (EHF) of PRO and its salts were calculated, and the relationships between these parameters and melting points and the solubility changes were analyzed. [ABSTRACT FROM AUTHOR]

Isostructural crystals are crucial for the development of high-performance functional materials and precise control over physicochemical properties, whereas the design of isostructural crystals is extremely challenging. In this work single-component isostructural crystals were obtained with the substitution of side-chain groups. High-quality single crystals of isostructural crystals methyl 2-amino-5-methylbenzoate (MAMB) and methyl 2-amino-5-methoxybenzoate (MAMOB) were harvested through sublimation crystallization. Their crystal structures were determined by single-crystal X-ray diffraction (SCXRD). Similar intermolecular interactions and packing modes suggested that MAMB and MAMOB are 3D isostructural, and the quantitative similarity parameters were calculated via the XPac program. Furthermore, these two obtained isostructural crystals exhibited similar blue light emission behaviors and solvation effects. [ABSTRACT FROM AUTHOR]

The preparation of a cocrystal is one of the effective strategies to tune the luminescence properties of organic crystals. In this work, four charge transfer cocrystals were constructed with isomeric substances of amino substituted dimethyl phthalates as the donors and 1,2,4,5-tetracyanobenzene as the acceptor. The emission range of the individual electron donors is from 400 nm to 505 nm, while all cocrystals have their emission redshift exceeding 100 nm. The tunable emission range of the charge transfer cocrystals is from 573 nm to 640 nm. All the obtained four cocrystals contain π–π stacking structures with the presence of π–π and C–H⋯π interactions. Fourier transform infrared spectroscopy and UV-vis spectroscopy demonstrated the presence of charge transfer interactions in the cocrystals. The tuning of the luminescence properties of the cocrystals was explained by the analysis of the crystal packing structure and the intermolecular interaction, and the distribution of frontier orbitals was obtained by DFT calculation. We believe our work is helpful to understand the relationship between the crystal structure and luminescence properties in the charge transfer cocrystals and provide guidance for the modulation of the luminescence properties. [ABSTRACT FROM AUTHOR]

The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor. Octadecylamine Hydrochloride (ODA), 1-Dodecylamine Hydrochloride (DAH) and Sodium 1-dodecanesulfonate (SDS) were selected to study their effect on the nucleation of potassium chloride. Focused Beam Reflectance Measurement was used to collect the nucleation-induced periods of KCl in the presence of flotation agents at different supersaturations. Then, empirical equations, classical nucleation theory and growth mechanism equations were employed for data analysis. It was found that the presence of flotation agents increased the nucleation sequence m, and m(ODA) > m(SDS) > m(DAH) > m(H2O). In addition, the interfacial energy data obtained using classical nucleation theory suggest that the flotation agents used in our paper promoted the homogeneous nucleation of KCl (reduced from 5.3934 mJ·m−2 to 5.1434 mJ·m−2) and inhibited the heterogeneous nucleation of KCl (increased from 2.8054 mJ·m−2 to 3.6004 mJ·m−2). This investigation also revealed that the growth of potassium chloride was consistent with the 2D nucleation-mediated growth mechanism, and the addition of flotation agent did not change the growth mechanism of potassium chloride. Finally, the particle size distribution results were exactly consistent with the order of nucleation order m. The study of nucleation kinetics and growth mechanisms of different flotation agents on potassium chloride can provide guidance for optimizing the production process of potassium chloride and developing new flotation agents. [ABSTRACT FROM AUTHOR]

This study combines theoretical models with experiments to analyze the impurity migration mechanism and obtain the key factors of separation optimization for the design of layer melt crystallization. The fractal slice model was used to explore pore structure formation and calculate the heat properties of the crystal layer. It was found that the fractal characteristics approached the features of Euclidean geometry with increasing porosity, and the thermal conductivity showed a linear decrease with the porosity. Three kinetic models were established based on the temperature difference to reveal quantitative correlations with the degree of supercooling (or superheating). The effects of the pore structure, kinetic behavior, and sweating intensity on the separation process are highlighted. Finally, this work analyzed the important roles of kinetic factors and impurity migration distribution, where a qualitative analysis revealed that the kinetic effect was important in impurity migration in the sweating process. [ABSTRACT FROM AUTHOR]

Mechanically flexible crystals are generally obtained based on weak interactions in the aromatic systems. Here, we reported the remarkable 2D elastic bending behaviors in a nonaromatic organic molecular crystal. The strong hydrogen bonding interactions are also verified to play a crucial role in the reversible bending. [ABSTRACT FROM AUTHOR]

Dynamic molecular crystals are thought to be an emerging functional material with enormous tunability in physicochemical properties. Here, a smart crystal, 6‐Chloronicotinic acid (6‐CNA), is reported, responding to heat stimulus by bending, splitting‐to‐self‐healing, and jumping, induced thermally by a reversible single‐crystal‐to‐single‐crystal phase transition. This phase transition proceeds by a well‐organized migration of the habit plane, which is reproducible after more than twenty phase transition cycles. The temperature function introduced externally can realize a reversible migration of the habit plane and also act as a jump switch. A comprehensive analysis of the microscopic observations demonstrates that the heterogeneity of phase transition and the homogeneity of self‐driven orientations account for the splitting‐to‐self‐healing. Utilization of the reversible phase transition of 6‐CNA single crystal can generate a pushing force that is > 104 times the gravitational force of the crystal, thus making 6‐CNA an actuator to drive the reversible movement of a glass plate. Both forms of these crystal materials are mechanically compliant in two dimensions and can be twisted in terms of requirement. This excellent actuation performance, reversibility of the phase transition, and soft nature make it a prospective candidate for robust single‐crystal actuators. [ABSTRACT FROM AUTHOR]

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 r c r i t and Δ G c r i t 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. [ABSTRACT FROM AUTHOR]

Carbon-based sensors for the detection of ascorbic acid (AA) and ferric ions have drawn a great deal of attention recently, owing to their excellent optical properties and good biocompatibility for biological applications. In this work, a series of nitrogen-doped carbon dots (NCDs) were fabricated by a microwave-assistant approach with a combination of dl-malic acid and urea as precursors. Under optimal experimental conditions, NCDs with an average size of 4.52 ± 0.05 nm were prepared, containing amino N and C–N functional groups on the surface of carbon cores. Optical analysis showed that the NCDs exhibited excitation-dependent and concentration-dependent emission properties. A single emission at 450 nm was observed with two luminescent centers at 280 and 370 nm for concentrations ranging from 0.02 to 0.08 mg/mL. Moreover, the NCDs were further used as a fluorescence sensor to detect AA and Fe3+ in solution. From the metal ion sensing research, Fe3+ demonstrated significant quenching abilities on NCDs with a detection limit of 1.9 μM. More importantly, the NCDs also showed an excellent quenching response by AA through the static quenching mechanism and inner filter effect with a detection limit of 2.6 μM. Additionally, the low cell toxicity against MA104 and 293T cells from both monkeys and humans were affirmed, respectively. Therefore, the NCDs developed in the present work provide a "turn-off" strategy for the highly sensitive detection of AA and Fe3+ ions and can be potentially applied in both environmental and biological systems. [ABSTRACT FROM AUTHOR]

Solubility has been widely regarded as a fundamental property of small molecule drugs and drug candidates, as it has a profound impact on the crystallization process. Solubility prediction, as an alternative to experiments which can reduce waste and improve crystallization process efficiency, has attracted increasing attention. However, there are still many urgent challenges thus far. Herein we used seven descriptors based on understanding dissolution behavior to establish two solubility prediction models by machine learning algorithms. The solubility data of 120 active pharmaceutical ingredients (APIs) in ethanol were considered in the prediction models, which were constructed by random decision forests and artificial neural network with optimized data structure and model accuracy. Furthermore, a comparison with traditional prediction methods including the modified solubility equation and the quantitative structure-property relationships model was carried out. The highest accuracy shown by the testing set proves that the ML models have the best solubility prediction ability. Multiple linear regression and stepwise regression were used to further investigate the critical factor in determining solubility value. The results revealed that the API properties and the solute-solvent interaction both provide a nonnegligible contribution to the solubility value. [ABSTRACT FROM AUTHOR]

2,4-Dichlorophenoxyacetic acid (2,4-D) is a kind of plant growth regulator which exhibits hormesis effects at low dosages, while high dosages adversely affect the exposed organisms and act as herbicide. 2,4-D has low solubility, therefore, it is a good candidate for crystal engineering research to improve its solubility. This paper presents the preparation of five new multicomponent crystals of 2,4-D, including three salts with imidazole (IMZ), 2-aminopyridine (AAP), and 3-aminopyridine (BAP), and two cocrystals with isonicotinamide (ISO) and pyrazinamide (PYM) as coformers (CCFs). The five multicomponent crystals were first characterized by single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Molecular interactions, crystal packing, and structure similarity analyses performed using Hirshfeld surface and CrystalCMP confirmed the charge-assisted H-bonding sites and structural similarity among the solved crystal structures. The stability tests show that all five multi-component crystals exhibit excellent stability within 12 weeks under accelerated storage conditions (40 °C and 75% RH). Moreover, all the five multicomponent crystals of 2,4-D exhibit increased solubility, especially (2,4-D)+(IMZ)− that increased the solubility of the resulting salt by 70 times compared to the free acid 2,4-D. From the perspective of single-crystal structure and intermolecular interaction, the reasons for these changes in physical and chemical properties are further clarified. [ABSTRACT FROM AUTHOR]

Dapsone, a sulfonamide, is used to treat tuberculosis, leprosy, malaria, Kaposi's sarcoma, dermatoses and AIDS-related pneumonia. The purpose of this paper is to study the new solid forms of dapsone by using the crystal engineering method of cocrystallization. Based on the design concept of supramolecular synthons, the "–NH2⋯Npyridine" supramolecular synthon was used. 1-(4 pyridyl)piperazine (PYR) was selected as the co-former to prepare (1 : 1) and (2 : 1) DAP-PYR cocrystals, and the corresponding crystal structures were obtained by single crystal X-ray diffraction. The resulting cocrystals were fully characterized by a range of analytical techniques, including powder X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, etc. It was found that (1 : 1) and (2 : 1) DAP-PYR cocrystals formed mainly depending on the initial feed ratio of raw materials, which could be transformed into each other by adding quantitative DAP or PYR after mechanical grinding. Molecular interaction and structure analyses performed by Hirshfeld surface and 2D fingerprint plot analyses confirmed that the formation of the supramolecular synthon is the contribution of hydrogen bonding. Furthermore, the molecular electrostatic potential surface and intermolecular binding energy were calculated to visually identify the molecular hydrogen bonding sites, and it revealed that the strong hydrogen bonding interaction of "–NH2⋯Npyridine" promoted the formation of DAP-PYR cocrystals. [ABSTRACT FROM AUTHOR]

Calcium D -pantothenate, also known as VB5, is one of the most important feed additives. It typically assumes a needle-like morphology that easily agglomerates, resulting in poor flowability and low bulk density. Here, we develop a route to prepare calcium D -pantothenate in a block-like morphology with good flowability and high bulk density. Also, the solvent-mediated phase transformation of calcium D -pantothenate methanol solvate (D-PC·MeOH) into D -pantothenate tetramethanol monohydrate (D -PC·4MeOH·H2O) was investigated by in situ ATR-FTIR spectrometry and Raman spectrometry, and the data was subsequently correlated by the Johnson–Mehl–Avrami model. Results demonstrate that the rate-controlling step was the nucleation and growth of D-PC·4MeOH·H2O. Careful control over the thermal transformation process of D-PC·4MeOH·H2O enabled the formation of solvent-free calcium D -pantothenate in a block-like morphology. Molecular dynamics simulations enabled a deeper understanding of the effects of temperature on the phase transformation process. This work provides a framework to scale the production of calcium D -pantothenate to industrial levels. [ABSTRACT FROM AUTHOR]

In this study, curcumin 1,4-dioxane solvates (CUR–DIO) were obtained in two molecular ratios of 1 : 1.5 (CUR–DIO-1.5) and 1 : 1 (CUR–DIO-1) at different temperatures. In the two single crystal structures, the molecular conformation of curcumin is a planar structure and a curved structure, respectively. Moreover, the length of the hydrogen bond between the curcumin molecule and the 1,4-dioxane molecule indicates that with the increase in the system temperature, the difficulty of solvate formation increases, the solvent ratio decreases, and the inter-molecular hydrogen bond energy increases. In addition, with the increase in temperature, the crystal morphology changes from spherulites to rod-shaped crystals. The hollow spherulites of CUR–DIO-1 were obtained at 25 °C, and based on the ReactRaman data and microscope recording, a new formation mechanism of hollow spherulites was proposed. The formation mechanism and preparation method of organic small molecule hollow spherulites will play an important role in promoting the application of the hollow spherulite structures in the fields of drug loading, slow release and multifunctional drugs. [ABSTRACT FROM AUTHOR]

The impact of two structural factors of sodium carboxylate additives on their ability to induce the selective crystallization of γ‐aminobutyric acid (GABA) Form‐II was investigated, namely, the number of –COO− groups and the types of R groups (chain alkyl, cyclic alkyl, or phenyl). It was found that the increase of –COO− groups caused the additives lose their inducing ability. This may be attributed to the fact that the increment of hydrophilic –COO− groups results in enhanced solvation and steric effect of additives, which makes additives unable to interact with GABA effectively. Additives with different R groups all can induce Form‐II but they exhibited varying inducing abilities. This could be due to the distinct results of competition between the attachment and detachment of different additives on the GABA growth end. [ABSTRACT FROM AUTHOR]

Boscalid, a commonly used fungicide, is mainly used for controlling gray mold, powdery mildew, and sclerotia. The aim of this study was to investigate the solid forms of boscalid systematically. The powder production of two anhydrous polymorphs (form I and form II) and monohydrate (H1) has been reported in the literature, while three novel solvates, i.e. S1 (1,4-dioxane solvate), S2 (N-methyl pyrrolidone solvate) and S3 (dimethyl sulfoxide solvate) have been obtained for the first time. The physicochemical properties of these six solid forms were fully characterized including power X-ray diffraction, scanning electron microscopy, Fourier transform-infrared spectroscopy, solid-state NMR, and thermal analysis. The crystal structures of all the six solid forms were determined from the single crystal data. The molecule conformations and packing arrangements in the crystal structures were analyzed and compared. Hirshfeld surface analysis was applied to reveal the intermolecular interactions. The packing coefficients of the crystal forms have been calculated to explain the formation of solvates. Finally, the desolvation process of solvates and the transformation relationship between different phases were explored. Meanwhile, the desolvation of solvate S2 leads to form II suitable for practical applications. [ABSTRACT FROM AUTHOR]

Levofloxacin is a fluoroquinolone and bears a broad-spectrum antibacterial effect. The polymorphism of levofloxacin was intensively studied, nevertheless, the landscape of polymorphs is not fully understood. Herein we reported for the first time the fully solved crystal structure of an anhydrous α form and three newly discovered solvates including n-propanol solvate, ethylene glycol solvate and acetic acid solvate. The successfully solved crystal structure of the anhydrous α form by single crystal X-ray diffraction was found to be in good agreement with the reported data by the SDPD (structure determination from powder X-ray diffraction data) method, but is significantly different from the one by the crystal structure prediction (CSP) approach. The comparison results suggest the wrong solved crystal structure of the α form using the CSP method. The newly reported n-propanol solvate, ethylene glycol solvate and acetic acid solvate of levofloxacin were fully characterized by powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, and single crystal X-ray diffraction (except for the acetic acid solvate). It was found that the solvent molecules of the n-propanol solvate fill the channels and interact weakly with the active pharmaceutical ingredient (API) molecules, while they play crucial roles in the stability of the crystal structure. Further, the phase transformations among different solid-state crystal forms of levofloxacin were investigated in detail by variable-temperature powder X-ray diffraction. The results reveal that all of the newly discovered solvates can be directly dehydrated to an anhydrous γ form, which eventually converted into an anhydrous α form during subsequent heating. [ABSTRACT FROM AUTHOR]

The incorporation of drug–drug salts is known as an attractive strategy to not only improve physicochemical properties but also extend the field of combination drug delivery. Mefenamic acid (MFA) and tolfenamic acid (TFA) belong to effective but poorly soluble anti-inflammatory drugs used for treating both humans and animals. Piperazine (PPZ) has anthelmintic activities with a serious hygroscopic problem. To improve the physicochemical properties of such drugs and seek possible drug combinations, herein, four novel MFA\TFA–piperazine (PPZ) drug–drug salts with different stoichiometry (2 : 1 and 1 : 1) were designed and synthesized. As we expected, the experiments proved that their solubilities and dissolution properties were much better than that of MFA and TFA. Among them, the apparent solubility of the MFA–PPZ salt (1 : 1) improved about 130 times more than that of MFA in a mixture of water and ethanol. Meanwhile, these salts were non-hygroscopic based on dynamic vapor sorption analysis. Moreover, the obtained crystals were fully analyzed by single-crystal X-ray diffraction (SXRD), Hirshfeld surface analysis and a solvent mediated phase transformation study, which provided a better understanding of the crystal structure. The MFA–PPZ salt (2 : 1) and TFA–PPZ salt (2 : 1) possessed a similar crystal structure and their solubilities were also similar. In addition, the incorporation of PPZ in the crystal lattice destroyed the dimer form in the original MFA\TFA crystal and resulted in the formation of salts through a new ionic hydrogen bond. After contact with the solvents, PPZ was more likely to interact with the solvent molecules, which may have led to the acceleration of dissolution. [ABSTRACT FROM AUTHOR]

A drug–drug anhydrous pharmaceutical salt containing tolbutamide {systematic name: 3‐butyl‐1‐[(4‐methylbenzene)sulfonyl]urea, TOL, C12H18N2O3S} and metformin (systematic name: 1‐carbamimidamido‐N,N‐dimethylmethanimidamide, MET, C4H11N5) was created based on antidiabetic drug combinations to overcome the poor pharmaceutical properties of the parent drugs. Proton transfer and the proportion of the two components were confirmed by 1H NMR spectroscopy and single‐crystal X‐ray diffraction analysis. Comprehensive characterization of the new pharmaceutical salt crystal, 2‐[(dimethylamino)(iminiumyl)methyl]guanidine (butylcarbamoyl)[(4‐methylbenzene)sulfonyl]azanide, C4H12N5+·C12H17N2O3S−, was performed and showed enhancement of the pharmaceutical properties, such as lower hygroscopicity and greater accelerated stability than the parent drug MET, and higher solubility and dissolution rate than TOL. The property alterations were correlated with the crystal packing features and potential hydrogen‐bonding sites through observed changes in the crystal structures. [ABSTRACT FROM AUTHOR]

Four new solvent-free forms and five solvates of the widely-used herbicide nicosulfuron were found. The crystal structures of the reported form II and two new solvates (methanol and acetonitrile) were revealed for the first time. The results showed that nicosulfuron is conformationally flexible and that nine conformations are involved in these three solid forms, leading to different intermolecular interactions and packing patterns. The relationship between the polymorphs and molecular conformations was discussed through crystal structure analyses. In addition, comprehensive characterization of these forms was carried out to study the desolvation process and stability. The results showed that temperature-induced desolvation led to the appearance of new polymorphs, and that the moisture-dependent stability of nicosulfuron improved significantly compared to the marketed form Ia. [ABSTRACT FROM AUTHOR]

Full comparison of the experimentally determined crystal structure of the levofloxacin anhydrous α form from single-crystal X-ray diffraction with all the predicted structures from the CSP approach was supplemented. The previous conclusion in regard to the accuracy of predicted structures by crystal structure prediction (CSP) reported in our article (N. Wei, L. Jia, Z. Shang, J. Gong, S. Wu, J. Wang and W. Tang, CrystEngComm, 2019, 21, 6196–6207) was improved. The comparison results indeed demonstrated great similarities in the space group, unit cell parameters and even crystal packing of the predicted structures at rank 2 in the Z′ = 1 list to the experimental α form, despite the minor structural differences in the molecular conformation and packing arrangement. It was found that the levofloxacin molecules take a less stable conformer in energy rather than the stable conformer as previously expected. [ABSTRACT FROM AUTHOR]

Abstract: Clopidogrel hydrogen sulfate is a famous antiplatelet agent for vascular disease. Forms I and II can be used as medicine. However, both forms exhibit low density and flowability. In addition, form I shows low polymorph stability. To solve these problems, spherical crystallization technologies were developed for the two forms. For form I, the mechanism was studied and turned out to be 2D nucleation and spherulitic crystal growth. In case of form II, the spherical crystallization process was based on agglomeration. The influence of temperature, acid, and crystal seed were investigated. The optimized spherical forms I and II showed much higher density and flowability as well as high polymorph stability. [ABSTRACT FROM AUTHOR]

Abstract: The solvate and the solvent‐free form of sulfadiazine (SD) were investigated. SD was found to exist in one solvent‐free form and the N‐methylpyrrolidone (NMP) solvate form. The NMP solvate was shown to be a channel‐type compound. The intrinsic properties of the solvents were used to evaluate the effects of solubility on the phase transformation of SD and the NMP solvate. The SD phase could transform to the NMP solvate by NMP‐mediated phase transformation, which was governed by crystallization of the NMP solvate. The crystalline NMP solvate could transform to the solvent‐free solid state through solid‐solid transformation upon heating or water penetration‐mediated phase transformation. The rate of this water penetration‐mediated phase transformation of the NMP solvate to SD was unusually fast. It can be used to obtain SD aggregates of well‐defined shape and good powder properties. [ABSTRACT FROM AUTHOR]

Daidzein (DAID), known as a phytoestrogen, is an important bioactive flavonoid isolated from soybean and pueraria. However, its poor solubility and low dissolution rate limit its clinical application. With the aim of finding a form with fit-for-purpose physicochemical properties, a comprehensive solid-state screening experiment was performed. As a result, three polymorphs were discovered and the single crystal structure of stable form II was revealed for the first time. Form II was obtained in solvents with high β and π* values, while form III was produced under opposite conditions. To clarify this phenomenon, intermolecular interactions were investigated through single crystal structure analysis, solvent property analysis and computational methods. The results demonstrated that the compact arrangement of DAID and the solvents used played a critical role in solution crystallization. Moreover, the physicochemical properties of these three polymorphs were fully characterized, and the powder dissolution behavior was determined in pure water and pH 1.2 and pH 6.8 buffer solutions. The newly discovered form II exhibited better thermal stability, lower moisture sorption and faster dissolution rate compared with the other forms. [ABSTRACT FROM AUTHOR]

We report here a unique method for the preparation of aggregated crystals with well-defined shape and size using a solvent penetration-mediated phase transformation. An unusually fast phase transformation of sulfadiazine was observed. The aggregated sulfadiazine crystals are obtained through a water penetration mediated transformation of sulfadiazine N-methyl pyrrolidone solvate. The aggregated particles keep the same shape and size of the parent crystals. [ABSTRACT FROM AUTHOR]

The latest developments of industrial crystallization in China are reviewed. This includes the introduction of representative scientists and institutions promoting the progress of Chinese industrial crystallization. Additionally, primary application fields related to industrial crystallization are outlined to give an overview of the current research trends in China. National and international industrial crystallization meetings held in China are also presented. Finally, the expectations for the future research activities in the field of industrial crystallization in China are briefly described. [ABSTRACT FROM AUTHOR]

Atorvastatin calcium (AC) spherical crystals were prepared by spherical agglomeration. CH2Cl2 acting as bridging liquid was added together with the drug solution or after the antisolvent precipitation process. Polymorph transformation in antisolvent crystallization and agglomeration processes was observed by focused-beam reflectance measurement (FBRM). The results suggested the occurrence of an immediate agglomeration when CH2Cl2 was added together with the drug solution. Size-controllable AC spherical crystals with improved flowability and compressibility can be obtained by adjusting the amount of CH2Cl2 and the stirring speed. The improved compaction behavior of the AC particles can be applied for direct tableting. A higher stirring speed can reduce the amount of bridging liquid which is required for effective agglomeration. It was a prerequisite for fine particles to be wetted by the bridging liquid in the spherical agglomeration process. [ABSTRACT FROM AUTHOR]

Powders of donepezil hydrochloride monohydrate (Form I) underwent isomorphic dehydration, losing 3% w/w water between 90% and 10% relative humidity (RH) without changing its powder X-ray pattern. Below 10% RH, additional dehydration occurred in conjunction with a reversible phase transition between the monohydrate state and a dehydrated state, with a 4.0% w/w loss to 0% RH. A combination of methods was used to understand the structural changes occurring during the desolvation process, including dynamic vapor sorption measurements, thermal analysis and powder X-ray diffraction. Form I showed the characteristics of the channel hydrate, whose non-isothermal dehydration behavior proceeds in two steps: (1) the loss of non-crystalline water adsorbed on the surface, and (2) the loss of one crystalline water in the channel. Dehydrated Form I is structurally similar to the monohydrate Form I. According to the heat of fusion and the crystal density criteria, the two crystal forms belonged to the univariant system, and the anhydrate (Form III) is stable. The dehydration kinetics was achieved from the TG-DTG curves by both the Achar method and the Coats-Redfern method with 15 frequently cited basic kinetic models. The dynamic dehydration processes for steps 1 and 2 were best expressed by the Zhuralev-Lesokin-Tempelman equation, suggesting a three-dimensional diffusion-controlled mechanism. [ABSTRACT FROM AUTHOR]

The solubilities of donepezil hydrochloride polymorphic form III in methanol, ethanol, 1-propanol and dimethyl formamide were measured at temperatures ranging from 278.15 to 333.15 K at atmosphere pressure using a gravimetrical method. The modified Apelblat model fitted the experimental data well with the root-mean-square deviations less than 6.287 × 10. The dissolution enthalpy and entropy of solute were predicted from the solubility data in different solvents using the van't Hoff equation. The relationships among solubility, temperature, the intermolecular force and hydrogen bonding between solute and solvent, and the viscosity of solvents were investigated. The viscosity and surface tension of solvents affect the dissolution enthalpy and entropy of donepezil hydrochloride polymorphic form III. [ABSTRACT FROM AUTHOR]

In this study, three solvates of sorafenib tosylate were obtained from methanol, ethanol and n-methyl-2-pyrrolidone (NMP) after solvate screening and the effect of solvent on the formation of solvate was analyzed. The solvents with high value of polarity/dipolarity and appropriate hydrogen bond donor/acceptor propensity are more likely to form corresponding solvates. The crystal structures of the solvates were elucidated for the first time by using single crystal X-ray diffraction data. The analysis results indicate that methanol solvate and ethanol solvate are isostructural and hydrogen bonds could be formed between solvent molecules and sorafenib tosylate molecules. Hirshfeld surface analysis was used to research the interactions in the solvates, and the results reveal that the H···H, C···H/H···C and O···H/ H···O contacts play the vital role in molecular packing. In addition, three solvates were characterized by polarized light microscope, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The solvates show different thermodynamic stability in methanol +NMP and ethanol +NMP mixtures. Furthermore, the desolvation of solvates was studied by hot stage microscope and discussed. [ABSTRACT FROM AUTHOR]