Crystal Polymorphism Research Articles

Epitaxial Calcite Morphology Modified in the Presence of Magnesium and Sulfate Ions

AbstractMagnesium and sulfate are a determinant key in CaCO3 mineralization. However, the works of the literature have failed to provide a clear understanding of how these ions influence the nucleation‐growth of CaCO3 precipitation. Our study uses an electrochemical method, having for principle to impose a dissolved oxygen reduction potential on gold (111) films. This technique that allows the exclusive and controlled crystallization of epitaxial calcite established an ideal system for the study of foreign ions influence. The polymorph, composition and morphology of crystals are characterized using scanning electron microscopy (SEM) coupled with X‐ray energy dispersive spectroscopy (EDS) and Raman spectroscopy. The results demonstrate that the increase of calcium concentration in calcocarbonic pure solution enhances the nucleation and then the growth of calcite crystals without affecting their morphology and their orientation. However, the magnesium directly modifies the surface morphology of calcite as a consequence of Mg substitution to calcium ions and the inhibitive effect of magnesium is assured by an incorporation mechanism. In the matter of sulfate ions influence, the experimental results indicate that SO42− slows down the epitaxial calcite nucleation by substituting itself to carbonate ions preferentially in the center of the crystals facets causing an enlargement of the lattice parameter.

Facilitating polymorphic crystallization of HMX through ultrasound and trace additive assistance

Low sensitivity octahydro-1,3,4,7-tetranitro-1,3,5,7-tetrazocine (HMX) has garnered significant attention from researchers due to its reduced shock sensitivity. However, the crystallization process poses challenges due to the high solidity and viscosity of the metastable α phase. Despite efforts to address this with additional energy sources like ultrasonic irradiation, prolonged exposure duration often results in small particle sizes, hindering the production of HMX with a consistent particle size distribution, thus limiting its applicability. To overcome these challenges, a method combining ultrasonic irradiation and trace H+ additive was proposed and investigated for their impact on the polymorphic transformation of HMX. The H+ additive was found to modify barriers, thus there was a lack of competitive driving force for the nucleation or growth of the metastable α form, thereby shortening the transformation pathway and duration. Moreover, the H+ additive significantly accelerated the nucleation rate of the β form (67.7 orders of magnitude faster with 0.10 wt ‰ H+) and the growth rate of β form HMX (5.8 orders of magnitude faster with 0.10 wt ‰ H+). While H+ additive alone was insufficient to induce spontaneous nucleation of the β form, combining it with short-duration ultrasonic irradiation further promoted β nucleation and shortened the polymorphic transformation duration (almost 20 orders of magnitude shorter). This rational approach led to effective control of the transformation process. The resulting low sensitivity HMX crystals exhibited varying mean sizes ranging from 20 to 340 μm, with purity exceeding 99.6 %, an apparent density greater than 1.8994 g/cm3, and few internal defects, fully meeting the requirements of low-sensitivity HMX, thus significantly expanding its potential applications. Our study sheds light on the mechanisms governing HMX polymorphic transformation in the presence of additives and ultrasonic irradiation, offering guidance for the rational control of this complex transformation.

Polymer-Assisted Polymorph Transition in Melt-Processed Molecular Semiconductor Crystals.

A previously unreported polymorph of 5,11-bis(triisopropylsilylethynyl)anthradithiophene (TIPS ADT), Form II, crystallizes from melt-processed TIPS ADT films blended with 16 ± 1 wt % medium density polyethylene (PE). TIPS ADT/PE blends that initially are crystallized from the melt produce twisted TIPS ADT crystals of a metastable polymorph (Form IV, space group P1̅) with a brickwork packing motif distinct from the slipstack packing by solution-processed TIPS ADT crystals (Form I, space group P21/c) at room temperature. When these films were cooled to room temperature and subsequently annealed at 100 °C, near a PE melting temperature of 110 °C, Form II crystals nucleated and grew while consuming Form IV. The growth rate and orientations of Form II crystals were predetermined by the twisting pitch and growth direction of the original banded spherulites in the melt-processed films of the blends. Notably, the Form IV → II transition was not observed during thermal annealing of neat TIPS ADT films without PE. The presence of the mobile PE phase during thermal annealing of TIPS ADT/PE blend films increases the diffusion rate of TIPS ADT molecules, and the rate of nucleation of Form II. Form IV crystals are more conductive but less emissive compared to Form II crystals.

Enhanced thermal stability of amorphous Al-Fe alloys by addition of Ce and Mn

The thermal stability of mechanically alloyed amorphous Al-Fe-based alloy powders, with nominal compositions Al82Fe16Ce2 and Al82Fe14Mn2Ce2, was investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and scanning electron microscopy (SEM) complemented by energy-dispersive x-ray spectroscopy (EDX). Analysis through DSC indicated that both Al82Fe16Ce2 and Al82Fe14Mn2Ce2 alloys undergo a two-stage crystallization process. Notably, the initial crystallization temperatures for the Al82Fe16Ce2 and Al82Fe14Mn2Ce2 alloys were determined to be approximately 525 °C and 550 °C, respectively. This high thermal stability is attributed to the delayed nucleation process induced by the presence of Ce and Mn within the Al-Fe matrix. During polymorphic crystallization, distinct phases such as β-AlFe, Al13Fe4 for Al82Fe16Ce2, and β-Al(Fe, Mn), Al13Fe4, Al10CeMn2 for Al82Fe14Mn2Ce2 were identified. Furthermore, post-annealing of these amorphous alloy powders at elevated temperatures of 600, 700, and 800 °C led to distinct morphological characteristics based on the alloy composition. For Al82Fe16Ce2, the particles preserved a nearly spherical morphology, with size distributions ranging from 1 to 5 μm. In contrast, for Al82Fe14Mn2Ce2, the particles exhibited an irregular shape with a broader size range of 1 to 15 μm.

Unraveling the crystallization mechanism of trinuclear Au complexes through crystal size-dependent luminescence

Abstract The trinuclear Au complex, DT4, demonstrates room-temperature phosphorescence (RTP) in the crystalline state, along with size-dependent polymorphism. The phase transition between the crystal polymorphs of DT4 can be directly observed in real time during crystal growth through changes in RTP color. This study aims to elucidate the crystallization mechanism of DT4, focusing specifically on determining the critical particle size at which crystal-to-crystal phase transitions occur during crystal growth.

Efficient Determination of Critical Water Activity and Classification of Hydrate-Anhydrate Stability Relationship

For a pair of hydrated and anhydrous crystals, the hydrate is more stable than the anhydrate when the water activity is above the critical water activity (awc). Conventional methods to determine awc are based on either hydrate-anhydrate competitive slurries at different aw or solubilities measured at different temperatures. However, these methods are typically resource-intensive and time-consuming. Here, we present simple and complementary solution- and solid-based methods and illustrate them using carbamazepine and theophylline. In the solution-based method, awc can be predicted using intrinsic dissolution rate (IDR) ratio or solubility ratio of the hydrate-anhydrate pair measured at a known water activity. In the solid-based method, awc is predicted as a function of temperature from the dehydration temperature and enthalpy obtained by differential scanning calorimetry (DSC) near a water activity of unity. For carbamazepine and theophylline, the methods yielded awc values in good agreement with those from the conventional methods. By incorporating awc as an additional variable, the hydrate-anhydrate relationship is categorized into four classes based on their dehydration temperature (Td) and enthalpy (ΔHd) in analogy with the monotropy/enantiotropy classification for crystal polymorphs. In Class 1 (ΔHd< 0 and Td ≥ 373 K), no awc exists. In Class 2 (ΔHd>0andTd≥373K), awc always exists under conventional crystallization conditions. In Class 3 (ΔHd<0andTd<373K), awc exists when T>Td. In Class 4 (ΔHd>0andTd<373K), awc exists only when T<Td. The hydrate-anhydrate pairs of carbamazepine and theophylline belong to Class 4.

Unknown crystal-like phases formed in an imidazolium ionic liquid: A metadynamics simulation study.

Crystal polymorphism of complex liquids plays a crucial role in industrial crystallization, food technology, pharmaceuticals, and materials engineering. However, the experimental identification of unknown crystal structures can be challenging, particularly for high-viscosity complex liquids, such as ionic liquids (ILs). In this study, we performed a molecular dynamics simulation coupled with metadynamics to investigate an imidazolium IL (1-alkyl-3-methylimidazolium hexafluorophosphates). The simulation employed two distinct radial-distribution functions, represented by Gaussian window functions as collective variables, and revealed at least two crystal-like phases distinct from the known α and β crystal phases typically formed by this IL. Additionally, the simulation unveiled a unique phase characterized by the ordered spatial arrangement of anion aggregations. These crystal-like and unique phases emerged regardless of the potential used. The simulation methodology presented here is broadly applicable for exploring unknown phases in complex systems and contributes to the design of functional materials, such as porous ILs for gas molecule capture and separation.

Radiation-enhanced crystallization of amorphous Nb2O5 films according to TEM with in situ video recording

Amorphous films are formed on substrates at room temperature in the process of anodic oxidation of niobium foil. The studies were carried out using methods of electron diffraction and “in situ” transmission electron microscopy (TEM) with video recording of structural changes. It was found that electron beam irradiation of the film with a dose rate (4–7)·104 e−/Å2·s inside the column of the electron microscope causes its layer polymorphous crystallization (LPC) with the formation of Nb2O5 crystals with hexagonal lattice. The dimensionless parameter of the relative crystallization length δ0≈ 5000 − 7000. The dependence on time of the crystal diameter is described by a power function with exponents of 1.55, 1.1 and 1.3. According to this the dependence of the fraction of the crystalline phase on time is described by a power function with exponents of 3.1, 2.2 and 2.6. This non-quadratic nature is explained with the formation of a domain superstructure in the low-temperature modification of α-Nb2O5 and phenomenon of polyamorphism in amorphous films.

High-Voltage Spinel Cathode Materials: Navigating the Structural Evolution for Lithium-Ion Batteries.

High-voltage LiNi0.5Mn1.5O4 (LNMO) spinel oxides are highly promising cobalt-free cathode materials to cater to the surging demand for lithium-ion batteries (LIBs). However, commercial application of LNMOs is still challenging despite decades of research. To address the challenge, the understanding of their crystallography and structural evolutions during synthesis and electrochemical operation is critical. This review aims to illustrate and to update the fundamentals of crystallography, phase transition mechanisms, and electrochemical behaviors of LNMOs. First, the research history of LNMO and its development into a LIB cathode material is outlined. Then the structural basics of LNMOs including the classic and updated views of the crystal polymorphism, interconversion between the polymorphs, and structure-composition relationship is reviewed. Afterward, the phase transition mechanisms of LNMOs that connect structural and electrochemical properties are comprehensively discussed from fundamental thermodynamics to operando dynamics at intra- and inter-particle levels. In addition, phase evolutions during overlithiation as well as thermal-/electrochemical-driven phase transformations of LNMOs are also discussed. Finally, recommendations are offered for the further development of LNMOs as well as other complex materials to unlock their full potential for future sustainable and powerful batteries.

Application of Different Animal Fats as Solvents to Extract Carotenoids and Capsaicinoids from Sichuan Chili.

Inspired by the proved dissolving power of vegetable oils for non-polar and low-polar natural compounds, animal fats with triglycerides as the major components were investigated as food-grade solvents in this study for the simultaneous extraction of carotenoids and capsaicinoids from Sichuan chili. The dissolving power of lard, beef tallow, chicken fat and basa fish oil in the extraction of er jing tiao chili was firstly compared, where animal oils with worse extraction ratios for carotenoids (0.79 mg/g in average) performed better for the extraction of capsaicinoids (0.65 mg/g in average). Furthermore, the solvent effect of animal fats on the oleo-extracts was evaluated in terms of fatty acid composition, oil quality indexes, crystal polymorphism, melting and crystallization behaviors, where no significant differences were observed between animal fats before and after extraction. The oxidative stability of animal fats could be 1.02- up to 2.73-fold enhanced after extraction and the pungency degree could reach the same spicy level as commercial hotpot oil. In addition, the Hansen solubility parameters of solvents and solutes were predicted for further theoretical miscibility study, which helps to make a better comprehension of the dissolving mechanism behind such oleo-extraction. Overall, animal fats demonstrated their considerable solvent power for extracting carotenoids and capsaicinoids simultaneously from Sichuan chili, which showed significant potential for developing a novel Sichuan spicy hotpot oil with enhanced flavor and stability.

Liquid Crystal Dimers and the Twist-Bend Phases: Non-Symmetric Dimers Consisting of Mesogenic Units of Differing Lengths.

The syntheses and characterisation of the 4-[{[4-({n-[4-(4-cyanophenyl)phenyl]-n-yl}oxy)phenyl]-methylidene}amino]phenyl-4-alkoxybenzoates (CBnOIBeOm) are reported with n=8 and 10 and m=1-10. The two series display fascinating liquid crystal polymorphism. All twenty reported homologues display an enantiotropic nematic (N) phase at high temperature. When the length of the spacer (n) is greater than that of the terminal chain (m), the twist-bend nematic (NTB) phase is observed at temperatures below the N phase. As the length of the terminal chain is increased and extends beyond the length of the spacer up to three smectic phases are observed on cooling the N phase. One of these smectic phases has been assigned as the rare twist-bend smectic C subphase, the SmCTB-α phase. In all the smectic phases, a monolayer packing arrangement is seen, and this is attributed to the anti-parallel associations of the like mesogenic units.

Sustainable deep eutectic solvents induced the polymorph selectivity and high purification efficiency

Deep eutectic solvents (DESs), as modern green solvents, have been examined as sustainable crystallization media in recent years. Nevertheless, their roles in affecting nucleation and polymorph control of crystal materials are still poorly understood. Herein, we report the use of DES for controlling polymorph crystallization and investigate systematically the mechanism of DES solvent characteristics on polymorph selectivity. Concomitant crystallization of sulfathiazole (STZ) polymorphs has been widely reported in organic solvents, while we found DES can improve its polymorph selectivity significantly. Pure forms II and IV were selectively and rapidly obtained from solvents containing [thymol][fatty acid] and [thymol][coumarin] DESs, respectively. The microstructural changes of DES exhibited dynamic regulatory effect on STZ polymorph selectivity. Analysis of 1H NMR, viscosity and computational simulations revealed that the DES hydrogen-bonding network structures were preserved for DES contents above 50 wt% in binary solvents, which affected the nucleation kinetics of STZ and its molecular assembly during crystallization process. Further mechanistic investigations suggested that DES hydrogen-bonding network structures exerted confinement effect and nucleation-templating effect through DES-solute interactions (hydrogen-bonding and π-π stacking interactions for [thymol][fatty acid] and [thymol][coumarin] systems, respectively), which limited the motion of solute molecules and delayed nucleation rate as well as induced the STZ nucleation toward specific orientations, thus achieving polymorph selectivity. In addition, DESs could be recycled and exhibited good reproducibility in achieving STZ polymorph purification. This study offers a sustainably effective strategy for polymorph purification of crystalline materials and promotes advance the fundamental understanding of DES solvent characteristics on polymorph control.

In situ analyses of crystallization behavior of 1,2,3-tripalmitoyl glycerol under static and dynamic thermal conditions

The crystallization behavior of 1,2,3-tripalmitoyl glycerol or PPP using differential scanning calorimetry (DSC), thermo-optical polarized light microscopy and in situ synchrotron radiation X-ray diffraction (SR-XRD) techniques was precisely examined under static isothermal and dynamic thermal treatments, and the results were compared with preceding studies. PPP was rapidly (15 °C min−1) cooled to target temperatures (from 40 to 59 °C) to determine the precise moment at which crystallization was initiated. Once crystallization ceased, polymorphic transformation and melting were analyzed during subsequent heating. α form was crystallized during isotherms from 40 to 46 °C, temperature at which it coexisted with β′ phase. The latter was solely formed from 47 to 53 °C, and polymorphic crystallization was directed to obtain exclusively most stable β at 54 °C and higher temperatures. Nucleation time values for the α, β′ and β polymorphs exhibited exponential growth type, and a good correlation was found between data obtained by DSC and SR-XRD. Dynamic experiments were based on the use of high (15 °C min−1), intermediate (2 °C min−1) and low (0.5 and 0.1 °C min−1) cooling and heating rates. Thermo-optical polarized light microscopy experiments also provided valuable information on microstructural changes occurring during polymorphic modifications. Less stable forms predominated at high cooling rates, whereas lower velocities leaded the polymorphic crystallization to obtain more stable forms.

Highly efficient in crystallo energy transduction of light to work.

Various mechanical effects have been reported with molecular materials, yet organic crystals capable of multiple dynamic effects are rare, and at present, their performance is worse than some of the common actuators. Here, we report a confluence of different mechanical effects across three polymorphs of an organic crystal that can efficiently convert light into work. Upon photodimerization, acicular crystals of polymorph I display output work densities of about 0.06-3.94 kJ m-3, comparable to ceramic piezoelectric actuators. Prismatic crystals of the same form exhibit very high work densities of about 1.5-28.5 kJ m-3, values that are comparable to thermal actuators. Moreover, while crystals of polymorph II roll under the same conditions, crystals of polymorph III are not photochemically reactive; however, they are mechanically flexible. The results demonstrate that multiple and possibly combined mechanical effects can be anticipated even for a simple organic crystal.

Observation of high-pressure polymorphs in bulk silicon formed at relativistic laser intensities

Silicon polymorphs with exotic electronic and optical properties have recently attracted significant attention due to their wide range of useful band gap characteristics. They are typically formed by static high-pressure techniques, which limits the crystal structures that can be made. This constitutes a major obstacle to study these polymorphs and their incorporation into existing technology. Approaches have attempted to address this shortcoming through using dynamic conditions and chemical precursor materials. Here, we report on an approach to create unusual crystal structures deep in the bulk of a silicon crystal by irradiating it with a laser pulse at ultrarelativistic intensity of up to 7.5×1019 W/cm2. Laser-generated electrons with MeV energy swiftly penetrate the target with speed close to the speed of light and deposit their energy into a large volume across the whole thickness of the sample. The relativistic electron current creates, via branching propagation and ionization, high-energy-density conditions for thermodynamically nonequilibrium phase transformation paths into new crystal polymorphs. X-ray microdiffraction and synchrotron x-ray diffraction analyses indicate, along with conventional dc-Si, the presence of exotic silicon structures in the bulk of the laser intact target volume. These structures are identified as body-centered bc8-Si, rhombohedral r8-Si, hexagonal-diamond hd-Si, and the tetragonal Si-VIII, all phases of Si that have previously been made through static techniques. Additionally, simple-tetragonal st12-Si and body-centered tetragonal bt8-Si were observed along with signatures of not yet identified diffraction spots. Both st12-Si and bt8-Si have only been observed in ultrafast laser microexplosion conditions at much lower laser intensity ∼1014 W/cm2 and within a micron-thin surface layer. The findings here are supported by direct observation of nanoparticles with high-resolution transmission electron microscopy and corresponding fast Fourier transform analysis of their interatomic distances. The presented analyses of absorbed laser energy, generation of the MeV electron current, and deposition of energy across the whole target thickness provide a solid basis for drawing the conclusion that the observed silicon polymorphs were produced because of laser-generated high-energy electrons fast-penetrating deeply into the bulk of silicon. In contrast to solid-solid transformations, the plasma-solid transitions offer a paradigm for the creation of exotic, high-energy density materials inside the bulk of the sample by using laser pulses at relativistic intensities. Published by the American Physical Society 2024

Shape-Dependent Optical Waveguides and Low-Threshold Lasers from Polymorphic Two-Dimensional Organic Single Crystals.

Organic single crystals (OSCs) with uniform morphologies and highly ordered molecular aggregations are promising for high-performance optoelectronic devices, such as organic solid-state lasers (OSSLs), organic light-emitting transistors (OLETs), and organic light-emitting diodes (OLEDs). However, manipulating OSC morphologies and aggregation is challenging. In this study, we synthesized two-dimensional (2D) OSCs of 4,4'-bis[(N-carbazole)styryl]biphenyl (BSBCz) in hexagonal and parallelogram microplate (H-MP and P-MP) forms. Both types exhibit H-aggregation in the 2D plate plane but with different molecular transition dipole moment (TDM) orientations. This leads to different photon coupling modes with H-MP and P-MP microcavities. H-MPs enable isotropic 2D-waveguiding, forming whispering gallery mode (WGM) resonators, while P-MPs create unidirectional waveguiding, forming Fabry-Pérot mode (FP) resonators. These resonators can generate low-threshold laser emissions at 467 and 473 nm, respectively, and exhibit superior lasing stability with a half-life exceeding 2 h. Our BSBCz microplate OSCs are attractive candidates to combine controlled organic microcavities with photon transporting for realizing future integrated optoelectronic devices.

Impact of nanoconfinement on the physical state and conductivity mechanisms of a 2-picolinium ionic liquid crystal

Hybrid solid-like materials prepared from the incorporation of liquid-like ionic conductors into nanoporous matrices could represent an advantage for a variety of electronic applications. Aiming to obtain such materials, three composites of the polymorphic ionic liquid crystal (ILC) 1-hexadecyl-2-methylpyridinium bromide ([C16-2-Pic][Br]), loaded in the mesoporous inorganic silica SBA-15 (∼6.8 nm in pore diameter), were prepared at guest–host weight fractions of ∼ 40, 60 and 80% (w/w) and investigated by different techniques: ATR-FTIR, BET, TGA, XRD and DSC. Complete amorphisation was achieved for the 40 and 60% composites, while the 80% preparation was stabilised in the low-T morph of native C16, being in the liquid state at room temperature. Furthermore, through Dielectric Relaxation Spectroscopy, the ionic conductivity of the three hybrid materials was characterised, allowing to deconvolute this property in a pure ohmic contribution (conductivity I) and the overlapping of ac − dc transition with interfacial polarisation resulting from the coexistence of the ionic liquid and the quasi-insulating inorganic matrix (conductivity II). From –20 to 20 °C, the conductivity and the corresponding charge migration are faster in all composites relative to the neat ILC, as deduced from the inferior radii of Nyquist arcs. The 60% preparation stood out from the other materials, exhibiting direct conductivity unaffected by electrode polarisation over a larger T-range, leading to the assumption of a nearly continuous silica-mediated charge migration pathway, which is never reached for the 40% composite, while, in the 80% preparation, some C16 deposits on the outer surface of the pores. Incorporation into the silica matrix proved to be a good strategy for the production of cost-efficient materials with long-term stabilisation of the ionic liquid in a single phase over a large range of temperatures, enabling the prediction of flow and conductive properties.

Polymorphism and White Light Emission of 1‐Bromo‐3,5,7‐triphenyladamantane Compared with 1,3,5,7‐Tetraphenyladamantane

AbstractHere we report our investigation of 1‐bromo‐3,5,7‐triphenyladamantane (1) and the elucidation of polymorphic crystals (1 A and 1 B) using single crystal X‐ray diffraction. In the monoclinic crystal system of 1 A (P21/n), we observed CH–π interactions, while Br⋅⋅⋅Br interactions are absent. Conversely, the Br⋅⋅⋅Br interactions are an apparent factor in the formation of the monoclinic crystal system of 1 B (R ). We compare our findings with 1,3,5,7‐tetraphenyladamantane (2), characterized by numerous CH–π interactions in the solid. Computational analyses were employed to investigate the interactions within the characteristic dimers present in the unit cells of 1 A and 1 B, including visualization of noncovalent interactions and the use of the atoms‐in‐molecules approach as well as MO analyses. These support the notion of London dispersion (LD) dimer‐dimer interactions in 1 A between the phenyl moieties, whereas 1 B exhibits additional dimer‐dimer Br⋅⋅⋅Br contacts. In contrast, the crystals of 2 are exclusively held together by CH–π stacking LD interactions, a feature absent in the polymorphs of 1. Both polymorphic forms of 1 emit white light when subjected to 900 nm continuous wave laser irradiation, displaying a subtle blue shift compared to 2. The absence of CH–π stacking interactions between the dimers of 1 causes a small red‐shift in the emission spectrum.

Diverse crystalline protein scaffolds through metal-dependent polymorphism.

As protein crystals are increasingly finding diverse applications as scaffolds, controlled crystal polymorphism presents a facile strategy to form crystalline assemblies with controllable porosity with minimal to no protein engineering. Polymorphs of consensus tetratricopeptide repeat proteins with varying porosity were obtained through co-crystallization with metal salts, exploiting the innate metal ion geometric requirements. A single structurally exposed negative amino acid cluster was responsible for metal coordination, despite the abundance of negatively charged residues. Density functional theory calculations showed that while most of the crystals were the most thermodynamically stable assemblies, some were kinetically trapped states. Thus, crystalline porosity diversity is achieved and controlled with metal coordination, opening a new scope in the application of proteins as biocompatible protein-metal-organic frameworks (POFs). In addition, metal-dependent polymorphic crystals allow direct comparison of metal coordination preferences.

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

AbstractContinuous crystallization of pharmaceuticals has been in the center of attention during the past two decades, with a more focus on the large‐scale production of active pharmaceutical ingredients. The increasing demand for pharmaceuticals requires high‐throughput production of drug crystals with different solubilities, stabilities, shapes, habits, polymorphs, and size distributions. With numerous advantages including low cost, ease of scale‐up, and superior control over polymorph and size distribution of drug crystals, antisolvent crystallization is one of the most promising crystallization methods recently attempted. However, it fails to deliver the required characteristic where the crystal systems tend to grow and for the preparation of metastable polymorphs. This review focuses on the most recent efforts to tackle these drawbacks by coupling antisolvent crystallization with cooling, supercritical‐assisted, microfluidics‐assisted, and membrane‐assisted crystallization. This systematic review aims to provide a concise summary of each coupled antisolvent technique and their positive and negative aspects. This review can be used as a guideline for pharmacist, biologists, and chemists, who are interested in the crystal engineering of pharmaceuticals to pave the way for further developments in this field.