Metastable Polymorph Research Articles

Impact of Polymers on the Kinetics of the Solid-State Phase Transition of Piracetam Polymorphs.

Metastable polymorphs of active pharmaceutical ingredients can occasionally be used to enhance bioavailability or make processing more convenient. However, the thermodynamic instability of metastable polymorphs poses a severe threat to the quality and performance of the drug products. In this study, we used hot-stage microscopy and powder X-ray diffraction to quantitatively analyze the kinetics of the solid-solid phase transition of piracetam (PCM) polymorphs in the absence and presence of several polymeric excipients. The Forms I and II of PCM are enantiotropically related polymorphs, and the transition point is 75 °C. We found that 1 wt % polymer can strongly affect the transformation rate of Form II to Form I of PCM above 75 °C. PVP K30 has the highest Tg and the strongest inhibitory effect on the transition, whereas PEG has the lowest Tg and the weakest effect on the transition. Below 75 °C, the addition of 1 wt % PEG can decrease the transformation rate from Form I to Form II of PCM by a few orders of magnitude, whereas no phase transition occurs in the presence of the other investigated polymers. The inhibitory effects of the same concentration of polymers on the kinetics of the solid-solid phase transition of piracetam polymorphs are considerably greater than those on the crystallization of PCM from the amorphous phase, especially at low temperatures. We propose that the low segmental mobility of polymers enriched between the crystalline phases can considerably inhibit the nucleation and growth of the stable form at the interface during the phase transition. Our findings deepen the current understanding of the mechanisms underlying the solid-state phase transition of polymorphic drugs in the presence of polymeric excipients, providing a promising formulation approach for stabilizing the metastable pharmaceutical polymorphs.

Stabilization of metastable calcium carbonate polymorphs on the surface of recycled cement paste particles: A two-step carbonation approach without chemical additives

In this study, a two-step carbonation method is developed to control the formation of calcium carbonate (Cc) polymorphs on the surface of recycled hardened cement paste (RHCP) without the use of chemical additives. In the first step, RHCP undergoes semi-dry carbonation under controlled humidity conditions, followed by wet carbonation at various temperatures in the second step. The results show that vaterite and aragonite are stabilized during the wet carbonation process, forming primarily on the surface of RHCP particles. The stabilization of the metastable Cc phases is driven by the synergistic effect of existing Cc seeds in the RHCP and the reaction temperature. A temperature range of 9–48 °C promotes the formation of vaterite, while higher temperatures (60–90 °C) lead to its dissolution. The calcite seeds present in RHCP do not enhance the formation of vaterite and aragonite during wet carbonation. This method offers a potential practical approach for valorizing concrete waste while capturing CO₂ from the atmosphere.

Phase-selective growth of κ- vs β-Ga2O3 and (InxGa1−x)2O3 by In-mediated metal exchange catalysis in plasma-assisted molecular beam epitaxy

Its large intrinsic polarization makes the metastable κ-Ga2O3 polymorph appealing for multiple applications, and the In-incorporation into both κ and β-Ga2O3 allows us to engineer their bandgap on the low-end side. In this work, we provide practical guidelines to grow thin films of single phase κ-, β-Ga2O3 as well as their (InxGa1−x)2O3 alloys up to x = 0.14 and x = 0.17, respectively, using In-mediated metal exchange catalysis in plasma-assisted molecular beam epitaxy (MEXCAT-MBE). The role of substrate temperature, oxidizing power, growth rate, and choice of substrate on phase formation and In-incorporation is investigated. As a result, the κ phase can be stabilized in a narrow deposition window irrespective of the choice of substrate [(i) α-Al2O3 (0001), (ii) 20 nm of (2̄01) β-Ga2O3 on α-Al2O3 (0001), and (iii) (2̄01) β-Ga2O3 single crystal]. Low growth rates/metal fluxes as well as growth temperatures above 700 °C tend to stabilize the β-phase independently. Lower growth temperatures and/or O-richer deposition atmospheres allow to increase the In-incorporation in both polymorphs. Finally, we also demonstrate the possibility to grow (2̄01) β-Ga2O3 on top of α-Al2O3 (0001) at temperatures at least 100 °C above those achievable with conventional non-catalyzed MBE, opening the road for better crystal quality in heteroepitaxy.

Carbonation curing of cement-based materials by using potassium glycine solution: Uniformly CO2 sequestration and secondary strengthening

In this research, an internal carbonation curing method was proposed to achieve inside-outside synergistic carbon capture and performance improvement of cement-based materials. Potassium glycine (KG) solution with various concentrations was used as the CO2 carrier. The results indicate that the addition of CO2-rich KG solution increases 7-d and 28-d compressive strength by 29.8% and 16.2%, as well as achieving an overall CO2 uptake of 4∼11% in cement paste. However, at higher KG concentrations, the rapidly generated amorphous calcium carbonate covers the surface of cement particles, which shortens the setting time and inhibits early-age hydration. The presence of carbamate in CO2-rich KG solution improves the stability of metastable CaCO3 polymorphs and prolongs the period of dissolution-recrystallization. Calcite generated by the slowed recrystallization within 14 days having a filling and binding ability in the cement matrix, significantly reducing porosity and providing a secondary strengthening effect.

Variations of silicon species, dissolution and crystallinity within sichars prepared under different heating rate

Silicon within Si-rich biochars (sichar) plays a crucial role in immobilizing heavy metals and providing slow-releasing bioavailable silicon for silicophilic plants. However, the impact of heating rate on the silicon properties and carbon‑silicon interactions in sichars remains unclear. In this study, rice husk was used as a silicon-rich biomass to prepare sichars at different heating rates (10, 30 and 60 °C per minute, and ultra-fast-pyrolysis), then experiments such as silicon concentration measurement, Raman and XRD characterization were conducted. The results showed that a faster heating rate reduced the carbon content during pyrolysis while promoted the formation of amorphous silica, resulting in a threefold increase in dissolved silicon in sichars prepared at 400 °C. Additionally, we observed the formation of a meta-stable SiO2 polymorph (tridymite) in rice husk-derived biochars under fast heating, differing from the previously observed quartz generated at slow heating rates. Regarding the CSi relationship, a faster heating rate facilitated the removal of the surface carbon layer, exposing the underlying silicon layer. This led to more soluble silicon species and less encapsulated silicon, resulting in a continuous release and cumulative silicon dissolution amount 1.2 times and 1.6–1.9 times higher, respectively, than those in slow heating rate-derived sichars. Consequently, this enhanced silicon uptake in rice seedlings. Our findings indicate that beyond pyrolysis temperature, the heating rate significantly affects the silicon species, silicon dissolution behavior, and carbon‑silicon relationships of biochar, ultimately determines the properties and applications of sichars.

All "Roads" Lead to Rocksalt Structure.

Rocksalt is the most common crystal structure among binary compounds. Moreover, no long-lived, metastable polymorphs are observed in compounds with the rocksalt ground state. We investigate the absence of polymorphism via first-principles random structure sampling and transformation kinetics modeling of three rocksalt compounds: MgO, TaC, and PbTe. Random structure sampling reveals that for all three systems the rocksalt basin of attraction covers much more of configuration space than any other, making it statistically the most significant structure. The kinetics modeling shows that virtually all other relevant structures, including most of the 457 known A1B1 prototypes, transform rapidly to rocksalt, making it the only option at ambient conditions. These results explain the absence of polymorphism in binary rocksalts, answer why rocksalt is the structure of choice for high-entropy ceramics and disordered ternary nitrides, and help understand/predict metastable states in crystalline solids more generally.

Direct Laser Writing Crystal Polymorphs of Organic Semiconductors for Phase Change Electronics.

The many diverse polymorphic behaviors observed in organic electronic materials offer opportunities to modulate electronic properties through reversibly switching crystal structures. Here, we access the prolific polymorphism observed in two-dimensional quinoidal terthiophene via laser writing to locally heat and direct the phase transitions. We access a metastable polymorph IV through rapid cooling and observe distinct symmetry as well as packing through grazing incidence X-ray diffraction (GIXD). Using our open-source PolyChemPrint patterning platform, we direct laser heating to initiate the IV-I transition, switching the conductance by >2 orders of magnitude. This is confirmed via a combination of GIXD and Raman spectroscopy. Finally, we demonstrate switching of transistor devices as well as discrete tuning of conductance via laser writing.

Nucleation Control and Isolation of Polymorphic Forms of Aspirin through an Efficient Template‐Assisted Swift Cooling Process

AbstractAspirin, a commonly used pharmaceutical therapeutic pharmacological substance, exhibits cross‐nucleation (intergrowth or overgrowth) of stable polymorphic Form‐I over the preferably required metastable polymorphic Form‐II, which creates a bottleneck issue in the solution crystallization of aspirin in most organic solvents and their mixtures. Controlling the overgrowth phenomenon is a key factor for designing the pharmaceutical drug material aspirin with desired properties. Hence, our present work chose a novel template‐assisted swift cooling crystallization with selected templates like copper‐wire and nylon 6/6 polymer, and also N‐N‐Dimethylformamide (DMF) as a solvent. The pure solution in the absence and the presence of a nylon 6/6 template in all the experimental supersaturation ranges achieves only thermodynamically stable polymorphic Form‐I of aspirin with slightly different morphologies. Contrarily, the presence of a copper‐wire template induces both stable and metastable polymorphs of aspirin depending on the level of supersaturation in the mother solution. The effect of templates on the nucleation kinetics of aspirin polymorphs is estimated using classical nucleation theory, and the determined values exactly match with experimental results. The polymorphic nature of the grown crystals is ascertained by powder X‐ray diffraction (PXRD), single crystal X‐ray diffraction (SCXRD), and differential scanning calorimetry (DSC) analyses.

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.

Selective Crystallization of l-Histidine Metastable Polymorphs: The Role and Mechanism of Additives

Selective Crystallization of <scp>l</scp>-Histidine Metastable Polymorphs: The Role and Mechanism of Additives

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.

Size Control of Biomimetic Curved-Edge Vaterite with Chiral Toroid Morphology via Sonochemical Synthesis.

The metastable vaterite polymorph of calcium carbonate (CaCO3) holds significant practical importance, particularly in regenerative medicine, drug delivery, and various personal care products. Controlling the size and morphology of vaterite particles is crucial for biomedical applications. This study explored the synergistic effect of ultrasonic (US) irradiation and acidic amino acids on CaCO3 synthesis, specifically the size, dispersity, and crystallographic phase of curved-edge vaterite with chiral toroids (chiral-curved vaterite). We employed 40 kHz US irradiation and introduced L- or D-aspartic acid as an additive for the formation of spheroidal chiral-curved vaterite in an aqueous solution of CaCl2 and Na2CO3 at 20 ± 1 °C. Chiral-curved vaterites precipitated through mechanical stirring (without US irradiation) exhibited a particle size of approximately 15 μm, whereas those formed under US irradiation were approximately 6 μm in size and retained their chiral topoid morphology. When a fluorescent dye was used for the analysis of loading efficiency, the size-reduced vaterites with chiral morphology, produced through US irradiation, exhibited a larger loading efficiency than the vaterites produced without US irradiation. These results hold significant value for the preparation of biomimetic chiral-curved CaCO3, specifically size-reduced vaterites, as versatile biomaterials for material filling, drug delivery, and bone regeneration.

Cationic substitution engineering in GdInO3 at A-site: Insights into phase evolution and search for compositionally tailored relaxors

The present work reports detailed structural and electrical studies on A-site substituted LaxGd1-xInO3 (0.0 ≤x ≤ 1.0) system with structurally different end members in search for tailored lead-free relaxors. The motivation is the possibility to manipulate the crystal structure to maneuver electrical properties in hexagonal GdInO3, a candidate for geometric ferroelectricity. The hybrid synthesis protocol involving gel-combustion led to stabilisation of metastable polymorphs in some nominal compositions due to kinetic stabilisation. Non-preference of La3+ for 7- fold coordinated A-site in hexagonal structure manifested in wide-ranging orthorhombic phase field prevailing even in Gd3+-rich region, also supported by theoretical studies. P-E studies on Gd3+-rich compositions exhibited hysteresis loop which suddenly became narrow for the nominal composition La0.4Gd0.6InO3 with very low remanent polarisation. This along with broad maximum exhibited in plot of dielectric constant vs temperature that shifts to higher T upon increasing frequency, for La0.4Gd0.6InO3, supports presence of relaxor-type behavior. Signature of hexagonal-type vibrations in otherwise bulk orthorhombic (by XRD) La0.4Gd0.6InO3 and anomalous trend in La/Gd vibrational mode along with narrowing down of Raman modes have been cited as plausible structural reasons for the relaxor behaviour. This has significance in context of structure-electrical property relationship leading to development of potential lead-free relaxors.

Carbon dioxide sequestration in mortars with excavated soil: Engineering performances and environmental benefits

Globally, substantial volume of excavated soils is generated during construction and demolition activities, which can be utilized in the manufacturing stabilized earth-based construction materials. Furthermore, increasing amount of CO2 is being released into the environment from growing industrial operations that can sequestered in earth-based materials without compromising the engineering properties. This article attempts to explore the effect of CO2 sequestration through accelerated carbonation curing on engineering properties, micro-structure and phase composition of cement-lime stabilized soil mortars. Lateritic soil (clay content of 42 %) is used to replace 25 % and 50 % of natural sand by mass. The experimental findings demonstrate an increase in CO2 uptake by 15–23 % and 33–40 % due to addition of 25 % and 50 % soil respectively compared to control (0 % soil). Precipitation of meta-stable calcium carbonates majorly contributes to the total CO2 uptake, accounting for 62–69 % and 78–87 % of the carbonates formed in 25 % soil-mortars and 50 % soil mortars. These are substantially higher compared to 40–50 % in the case of control mixes. The mentioned finding is attributed to the formation of additional calcium-silicate-hydrate and calcium-aluminate-hydrate due to clay-lime reaction, that binds CO2 and precipitate meta-stable polymorphs of calcium carbonate. Addition of lime and carbon sequestration are found to substantially enhance 1-day strength of cement-soil and cement-lime-soil mortars by 31–36 %, although no prominent effect at 7-day and 28-day marks are observed. Furthermore, capillary water absorption at 28-day age is reduced by 18–31 % in lime-added cement-soil mortars compared to the ones without lime, that reduces moisture sensitivity of the mortars. Overall, the carbon sequestered mortars demonstrate satisfactory strength (20–37 MPa) and water absorption performance of the stabilized mortars for masonry applications, which will provide a promising means to manufacture low-carbon and more durable construction products.

Improved heteroepitaxy of κ-Ga2O3 on c-plane sapphire by initial mist flow stabilization during mist chemical vapor deposition

Kappa-phase gallium oxide (κ-Ga2O3) is a metastable gallium oxide polymorph and an ultrawide bandgap semiconductor with potential applications in various electronic and optoelectronic devices. In this study, we present the effect of mist flow stabilization during the initial stages of mist chemical vapor deposition process on the crystal quality of heteroepitaxial thin films of κ-Ga2O3 grown on c-plane sapphire. Two κ-Ga2O3 films were grown using the same growth parameters with the only differing factor being the stabilization of the initial mist flow. Structural and optical properties of the films were characterized. Both processes resulted in epitaxial growth; however, controlling the initial mist flow leads to an improved Ga2O3/Al2O3 interface and superior crystal quality. The film grown with regulated mist flow exhibited an optical bandgap of 4.93 eV, a smooth surface with a root mean square roughness of 1.56 nm and a rocking curve full-width half-maximum value of 0.17°. Also, Ti/Au deposition on κ-Ga2O3 resulted in an interface resembling that of β-Ga2O3 and Ti/Au, explaining previous reports of ohmic behavior between κ-Ga2O3 and Ti/Au contacts.

Selective formation of metastable polymorphs in solid-state synthesis.

Metastable polymorphs often result from the interplay between thermodynamics and kinetics. Despite advances in predictive synthesis for solution-based techniques, there remains a lack of methods to design solid-state reactions targeting metastable materials. Here, we introduce a theoretical framework to predict and control polymorph selectivity in solid-state reactions. This framework presents reaction energy as a rarely used handle for polymorph selection, which influences the role of surface energy in promoting the nucleation of metastable phases. Through in situ characterization and density functional theory calculations on two distinct synthesis pathways targeting LiTiOPO4, we demonstrate how precursor selection and its effect on reaction energy can effectively be used to control which polymorph is obtained from solid-state synthesis. A general approach is outlined to quantify the conditions under which metastable polymorphs are experimentally accessible. With comparison to historical data, this approach suggests that using appropriate precursors could enable targeted materials synthesis across diverse chemistries through selective polymorph nucleation.

In situ atomic-resolution study of transformations in double polymorph γ/β-Ga2O3 structures

In situ TEM heating studies of double γ/β-Ga2O3 polymorph structures revealed γ-to-β polymorph transition via the formation of β-Ga2O3 domains.

Controlled synthesis and structure characterization of a new fluconazole polymorph using analytical techniques and multivariate method

In the crystallization and search for higher multicomponent forms of fluconazole (FLZ), a metastable FLZ polymorph (concomitant) that manifests in the same crystallization system and transforms into the stable FLZ form (II) after the lyophilization process was observed. In this report, we demonstrated and showed how this FLZ polymorph 10 (Mw = 306.79 g/mol) of the monoclinic C2 space group was detected and reproduced through a controlled lyophilized experiment, and modeled differentiation between vibrational and absorption modes of FLZ functionalities like C=O, OH, –CH2 and –NH. The FLZ polymorph shows strong O–H···N and weak C−H···X (X = N, and F) hydrogen bond and the presence of pi-pi bond interactions in the overlapping triazole rings. The combination of vibrational spectroscopic techniques (Raman/FT-IR) and principal component analysis (PCA) aid the development of important models for polymorph screening and identification. In addition, X-ray diffraction (powder and single crystal) techniques support the polymorph characterization and structure depiction. The PCA models and X-ray diffraction analyses confirmed the newness of FLZ polymorph 10, and further solid-state characterization using thermal techniques (DSC and TGA) affirmed its uniqueness and novelty. Finally, the thermal stability and solubility studies on the new FLZ polymorph were determined to understand its structure properties and compare these with previously reported polymorphs of FLZ.

A p-type dopable ultrawide-bandgap oxide

A major shortcoming of ultrawide-bandgap (UWBG) semiconductors is unipolar doping, in which either n-type or p-type conductivity is typically possible, but not both within the same material. For UWBG oxides, the issue is usually the p-type conductivity, which is inhibited by a strong tendency to form self-trapped holes (small polarons) in the material. Recently, rutile germanium oxide (r-GeO2), with a band gap near 4.7 eV, was identified as a material that might break this paradigm. However, the predicted acceptor ionization energies are still relatively high (∼0.4 eV), limiting p-type conductivity. To assess whether r-GeO2 is an outlier due to its crystal structure, the properties of a set of rutile oxides are calculated and compared. Hybrid density functional calculations indicate that rutile TiO2 and SnO2 strongly trap holes at acceptor impurities, consistent with previous work. Self-trapped holes are found to be unstable in r-SiO2, a metastable polymorph that has a band gap near 8.5 eV. Group-III acceptor ionization energies are also found to be lowest among the rutile oxides and approach those of GaN. Acceptor impurities have sufficiently low formation energies to not be compensated by donors such as oxygen vacancies, at least under O-rich limit conditions. Based on the results, it appears that r-SiO2 has the potential to exhibit the most efficient p-type conductivity when compared to other UWBG oxides.

Screening and Discovery of Metal Compound Active Sites for Strong and Selective Adsorption of N2 in Air.

Photocatalytic nitrogen fixation has the potential to provide a greener route for producing nitrogen-based fertilizers under ambient conditions. Computational screening is a promising route to discover new materials for the nitrogen fixation process, but requires identifying "descriptors" that can be efficiently computed. In this work, we argue that selectivity toward the adsorption of molecular nitrogen and oxygen can act as a key descriptor. A catalyst that can selectively adsorb nitrogen and resist poisoning of oxygen and other molecules present in air has the potential to facilitate the nitrogen fixation process under ambient conditions. We provide a framework for active site screening based on multifidelity density functional theory (DFT) calculations for a range of metal oxides, oxyborides, and oxyphosphides. The screening methodology consists of initial low-fidelity fixed geometry calculations and a second screening in which more expensive geometry optimizations were performed. The approach identifies promising active sites on several TiO2 polymorph surfaces and a VBO4 surface, and the full nitrogen reduction pathway is studied with the BEEF-vdW and HSE06 functionals on two active sites. The findings suggest that metastable TiO2 polymorphs may play a role in photocatalytic nitrogen fixation, and that VBO4 may be an interesting material for further studies.