Solid-state Dehydration Research Articles

Sodium salt hydrate crystals of nonsteroidal anti-inflammatory drugs: structure and solid-state dehydration transition relationship

Sodium salt hydrate crystals of nonsteroidal anti-inflammatory drugs: structure and solid-state dehydration transition relationship

Dehydration of Niclosamide Monohydrate Polymorphs: Different Mechanistic Pathways to the Same Product.

Many active pharmaceutical ingredients (APIs) can crystallize as hydrates or anhydrates, the relative stability of which depends on their internal structures as well as the external environment. Hydrates may dehydrate unexpectedly or intentionally, though the molecular-level mechanisms by which such transformations occur are difficult to predict a priori. Niclosamide is an anthelmintic drug on the World Health Organization's "List of Essential Medicines" that crystallizes in two monohydrate forms: HA and HB. Through complementary time-resolved synchrotron powder X-ray diffraction and thermogravimetric kinetic studies, we demonstrate that the two monohydrates dehydrate via distinctly different solid state pathways yet yield the same final anhydrate phase. Water loss from HA via diffusion yields an isomorphous desolvate intermediate which can rearrange to at least two different polymorphs, only one of which exhibits long-term stability. In contrast, dehydration of HB proceeds via a surface nucleation process where simultaneous water loss and product formation occur with no detectable crystalline intermediates. Comparative analysis of the two systems serves to highlight the complex relationship between lattice structure and solid state dehydration processes.

Unusual shape-preserved pathway of a core-shell phase transition triggered by orientational disorder.

The ubiquitous presence of crystal defects provides great potential and opportunities to construct the desired structure (hence with the desired properties) and tailor the synthetic process of crystalline materials. However, little is known about their regulation role in phase transition and crystallization pathways. It was generally thought that a phase transition in solution proceeds predominantly via the solvent-mediated phase-transformation pathway due to energetically high-cost solid-state phase transitions (if any). Herein, we report an unprecedented finding that an orientational disorder defect present in the crystal structure triggers an unusual pathway of a core-shell phase transition with apparent shape-preserved evolution. In the pathway, the solid-state dehydration phase transition occurs inside the crystal prior to its competitive transformation approach mediated by solvent, forming an unconventional core-shell structure. Through a series of combined experimental and computational techniques, we revealed that the presence of crystal defects, introduced by urate tautomerism over the course of crystallization, elevates the metastability of uric acid dihydrate (UAD) crystals and triggers UAD dehydration to the uric acid anhydrate (UAA) phase in the crystal core which precedes with surface dissolution of the shell UAD crystal and recrystallization of the core phase. This unique phase transition could also be related to defect density, which appears to be influenced by the thickness of UAD crystals and crystallization driving force. The discovery of an unusual pathway of the core-shell phase transition suggests that the solid-state phase transition is not necessarily slower than the solvent-mediated phase transformation in solution and provides an alternative approach to constructing the core-shell structure. Moreover, the fundamental role of orientational disorder defects on the phase transition identified in this study demonstrates the feasibility to tailor phase transition and crystallization pathways by strategically importing crystal defects, which has broad applications in crystal engineering.

Time-Resolved Cooperative Motions in the Solid-State Dehydration of Thymine Hydrate

Many organic compounds can exist in hydrated and anhydrous crystalline forms, each of which exhibits its own different set of physical properties. This makes dehydration–rehydration processes an im...

Atomic force microscopy to identify dehydration temperatures for small volumes of active pharmaceutical ingredients

The environmental conditions associated with changing the hydration state of active pharmaceutical ingredients (API) are crucial to understanding their stability, bioperformance, and manufacturability. Identifying the dehydration event using < 1 μg of material is an increasingly important challenge. Atomic Force Microscopy indentation mapping is implemented at controlled temperatures between 25 and 100 °C, for nanoscale volumes of hydrated APIs exhibiting distinct dehydration behavior and anhydrous APIs as controls. For caffeine hydrate and azithromycin dihydrate, the relative mechanical modulus increases ~10-fold at dehydration temperatures. These are confirmed by conventional macroscopic measurements including Variable Temperature Powder X-ray Diffraction, Thermogravimetric Analysis, and Differential Scanning Calorimetry. Conversely, no such mechanical transition is observed for anhydrous ibuprofen or a proprietary anhydrous compound. AFM-based mechanical mapping is therefore demonstrated for small-volume determination of temperature-induced solid-state dehydration events, which may enable spatial or temporal mapping for future studies of dehydration mechanisms and kinetics as a function of commercially relevant nanoscale heterogeneities.

Novel anhydrous solid-state form of Azathioprine: The assessing of crystal structure by powder X-Ray diffraction, Infrared Absorption Spectroscopy and Raman scattering

Azathioprine (Imuran), one of the oldest immunosuppressants, having been used in transplantation since the early 1960`s, is known to have only two crystal forms: an anhydrous form and a dihydrate phase. We report the crystal structure of a new anhydrous solid-state form of Azathioprine, determined directly form powder X-Ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. The new anhydrous polymorph is accessible only by a solid-state dehydration process of the readily obtained monohydrate form of Azathioprine, the form for which a crystal structure has not previously been reported. The IR and Raman spectra confirmed the results obtained from X-Ray diffraction indicating the presence of all functional groups involved in intermolecular hydrogen bonding which dictates different arrangement of molecules in the structural packing.

Combining the Advantages of Powder X-ray Diffraction and NMR Crystallography in Structure Determination of the Pharmaceutical Material Cimetidine Hydrochloride

We report the crystal structure of the anhydrous phase of cimetidine hydrochloride, determined directly from powder X-ray diffraction data. The material was prepared by dehydration of the readily obtained monohydrate form of cimetidine hydrochloride, the only form for which a crystal structure has previously been reported. As such, solid-state dehydration processes typically yield the product phase as a microcrystalline powder, and structure determination was carried out directly from powder X-ray diffraction data, using the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement. The structure determined from powder X-ray diffraction was further validated by calculating solid-state 13C NMR data for the crystal structure (using first-principles periodic DFT techniques within the GIPAW approach) and assessing the quality of agreement with the corresponding experimental solid-state 13C CPMAS NMR data. This strategy provides a robust vindication of the correctness of the crystal structure by assessing the quality of agreement of the structure both with experimental powder X-ray diffraction data and with experimental solid-state 13C NMR data.

Hydrogen-Bond Reorganization of a Solid-State Dehydration Process in a Salt of Tris(hydroxymethyl)aminomethane and Sulfosalicylic Acid, Investigated by Powder X-ray Diffraction

Hydrated solid salt of tris(hydroxymethyl)aminomethane (THAM) and sulfosalicylic acid (SA) undergoes a facile solid-state dehydration process upon heating, in which single crystals of the hydrated phase transform to a microcrystalline powder of an anhydrous product phase. The structural properties of the anhydrous phase have been determined directly from powder X-ray diffraction data, allowing rationalization of the structural changes associated with the dehydration process. The dehydration process is associated with substantial reorganization of the hydrogen bonding arrangement, while most hydrogen bonds related to SA ion are actually preserved in the transformation. The process relating to the formation and decomposition of a salt formed by SA and THAM—hydrated and anhydrous states was investigated and discussed in the paper.

Theoretical and experimental study of the vibrational spectra of liroconite, Cu2Al(AsO4)(OH)4∙4H2O and bayldonite, Cu3Pb[O(AsO3OH)2(OH)2

Liroconite and bayldonite were studied with vibrational (IR and Raman) spectroscopy, thermal analysis methods and X-ray powder diffraction. In aim to undertake correct spectral interpretation, solid-sample ATR spectra, IR transmission spectra in KBr (at room temperature and liquid nitrogen temperature), and IR spectra in non-volatile inert paraffin oil-Nujol and in fluorinated hydrocarbon oil-Fluorolube, were collected. The lowering of the symmetry of the AsO4 group as a result of the replacement of the O atom by an OH group in bayldonite resulted in band splitting manifested with the enhanced number of the AsO/OH stretching bands compared to the reduced number of AsO stretching bands in liroconite. In addition, conduced thermal analysis determined the mineral thermal stability and depicted the process of solid-state dehydration. Quantum theoretical study based on pseudopotential plane-wave density functional theory provided a support to the empirical band assignments.

Localized, solid-state dehydration associated with the Varberg charnockite intrusion, SW Sweden

The mineralogy, petrology, and fluid inclusion chemistry of two charnockite patches within a distance of 4–5km of the Varberg magmatic charnockite intrusion, SW Sweden, are investigated and described utilizing SEM, EMPA, and fluid inclusion microthermometry. Garnet–clinopyroxene (890–930°C), garnet–amphibole (600–800°C), and garnet–biotite (670–860°C) Fe–Mg exchange thermometry indicates high temperatures for charnockite Patch I compared to relatively lower garnet–orthopyroxene, garnet–amphibole, and garnet–biotite temperatures of 500 to 600°C for charnockite Patch II. Plagioclase in the charnockitic patches tends to be more anorthitic and less albitic (XAn=0.20, XAb=0.76) than in the surrounding regional granitic gneiss (XAn=0.13, XAb=0.84). Replacement antiperthite is commonly found in unrelated plagioclase grains from either patch compared to the regional granitic gneiss where it is relatively rare. In either patch, K-feldspar is considerably less albitic (XKfs=0.90–0.92, XAb=0.05–0.10) compared to K-feldspar from the regional granitic gneiss. It can also be found as micro-veins along quartz grain rims. Both patches are dominated by clinopyroxene as opposed to orthopyroxene. Garnet, biotite, and amphibole and in both charnockite patches tend to have lower Fe and correspondingly higher Mg values compared with garnet, biotite, and amphibole from the surrounding regional granitic gneiss. Fluorapatite tends to be relatively enriched in Cl and depleted in (Y+REE) compared with fluorapatite from the regional granitic gneiss. Fluid inclusions in charnockite Patches I and II are dominantly carbonic similar to what is seen for the Varberg charnockite. In addition to quartz, relatively high-density carbonic inclusions are also preserved in garnet and in fluorapatite. It is presumed that pure carbonic fluids must have once coexisted with relic magmatic H2O–CO2–NaCl fluids at peak metamorphic conditions. The most likely scenario suggests that charnockite Patches I and II were formed during the later stages of crystallization of the Varberg charnockite magmatic body during which copious amounts of CO2-rich fluids with a brine (CaCl2-dominated) component were expelled into the country rock via pegmatoid segregations both within and in the immediate surroundings of the charnockite body. Patch I appears to represent the extension of a pegmatoid segregation, whereas Patch II appears to represent fluid-induced lower temperature, solid-state dehydration. Transport was facilitated via a system of tectonic fissures and fractures generated in the regional migmatized granitic gneiss during its emplacement. Within the scope of what is known, these two charnockite patches fall into the generally observed parameters for localized dehydration zones in general.

Numerical simulations of CO2 migration during charnockite genesis

Charnockite is considered to be generated either through the dehydration of granitic magma by CO2 purging or by solid-state dehydration through CO2 metasomatism during granulite facies metamorphism. To understand the extent of dehydration, CO2 migration is quantitatively modeled in silicate melt and metasomatic fluid as a function of temperature, H2O wt%, pressure, basal CO2 flux and dynamic viscosity. Numerical simulations show that CO2 advection through porous and permeable high-grade metamorphic rocks can generate dehydrated patches close to the CO2 flow path, as illustrated by the occurrences of ``incipient charnockites.'' CO2 reaction-front velocity constrained by field observations is 0.69 km/m.y., a reasonable value, which matches well with other studies. On the other hand, temperature, rate of cooling, and basal CO2 flux are the critical parameters affecting CO2 diffusion through a silicate melt. CO2 diffusion through silicate melt can only occur at temperature greater than 840 degrees C and during slow cooling (<= 3.7 x 10(-5) degrees C/yr), features that are typical of magma emplacement in the lower crust. Stalling of CO2 fluxing at similar to 840 degrees C explains why some deep-level plutons contain both hydrous and anhydrous (charnockitic) mineral assemblages. CO2 diffusion through silicate melt is virtually insensitive to pressure. Addition of CO2 basal flux facilitates episodic dehydrated melt migration by generating fracture pathways.

The potential role of fluids during regional granulite-facies dehydration in the lower crust

High-grade dehydration of amphibolite-facies rocks to granulite-facies is a process that can involve partial melting, fluid-aided solid-state dehydration, or varying degrees of both. On the localized meter scale, solid-state dehydration, due to CO2-rich fluids traveling along some fissure or crack and subsequently outwards along the mineral grain boundaries of the surrounding rock, normally is the means by which the breakdown of biotite and amphibole to orthopyroxene and clinopyroxene occur. Various mineral textures and changes in mineral chemistry seen in these rocks are also seen in more regional orthopyroxene-clinopyroxene-bearing rocks which, along with accompanying amphibolite-facies rocks, form traverses of lower crust. This suggests that solid-state dehydration during high-grade metamorphism could occur on a more regional scale. The more prominent of these fluid-induced textures in the granulite-facies portion of the traverse take the form of micro-veins of K-feldspar along quartz grain boundaries and the formation of monazite inclusions in fluorapatite. The fluids believed responsible take the form of concentrated NaCl- and KCl- brines from a basement ultramafic magma heat source traveling upwards along grain boundaries. Additional experimental work involving CaSO4 dissolution in NaCl-brines, coupled with natural observation of oxide and sulfide mineral associations in granulite-facies rocks, have demonstrated the possibility that NaCl-brines, with a CaSO4 component, could impose the oxygen fugacity on these rocks as opposed to the oxygen fugacity being inherent in their protoliths. These results, taken together, lend credence to the idea that regional chemical modification of the lower crust is an evolutionary process controlled by fluids migrating upwards from the lithospheric mantle along grain boundaries into and through the lower crust where they both modify the rock and are modified by it. Their presence allows for rapid mass and heat transport and subsequent mineral genesis and mineral re-equilibration in the rocks through which they pass.

Synthesis and electrochemical studies of layer-structured metastable αI-LiVOPO4

The layer structured αI-LiVOPO4 was obtained via a two step chemical synthesis. In the first step, a hydrated phase, LiVOPO4·2H2O, was obtained by a simple hydrothermal route at 120 °C. Single crystal X-ray diffraction analysis revealed the structure of LiVOPO4·2H2O to be orthorhombic with lattice parameters: a = 8.9454(7) A, b = 9.0406(7) A and c = 12.7373(10) A. Dehydration of the parent compound led to its structural transformation to tetragonal αI-LiVOPO4, which was only identified previously during the lithium insertion in VOPO4. We have investigated the solid-state dehydration of LiVOPO4·2H2O and proposed a possible mechanism for the crystal structure transformation. Electrochemical characterization of this rarely studied tetragonal phase revealed its good lithium cycling at high operating voltage. Galvanostatic charge–discharge cycling of αI-LiVOPO4 was studied in a voltage window of 2.5–4.5 V, which shows a stable reversible capacity of 103(±3) mA h g−1 at a current density of 16 mA g−1 (0.1 C). At higher current rates, although it exhibited good cyclability, the capacity was found to decrease with increasing current rates. The long term cycling stability of the above material was demonstrated at a current rate of 0.5 C up to 200 cycles.

Structural Chemistry of a New Chiral Anhydrous Phase of Ru(bipy)3(ClO4)2Established from Powder X-ray Diffraction Analysis

A new anhydrous chiral phase of Ru(bipy)3(ClO4)2 (bipy = 2,2′-bipyridine) has been prepared both by mechanical grinding followed by annealing of the known chiral hydrate phase of this material and by solid-state dehydration of the chiral hydrate phase at high temperature. The new phase is obtained from these processes as a microcrystalline powder, thus limiting the opportunity to carry out structural characterization by single-crystal X-ray diffraction. Instead, our structure determination of the new chiral anhydrous phase has exploited the capabilities of modern powder X-ray diffraction techniques, employing the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement. The structural properties of the chiral anhydrous phase are discussed, particularly with regard to assessing the structural relationship to the parent hydrate phase.

A continuous process for solid-state dehydration, amorphization and recrystallization of metoclopramide HCL monohydrate studied by simultaneous DSC-FTIR microspectroscopy

The purpose of this study was to investigate the thermal-induced solid-state characterization of metoclopramide hydrochloride monohydrate (MCP H2O) by using a combination of differential scanning calorimetry (DSC) and Fourier-transform infrared (simultaneous DSC-FTIR) microspectroscopy. The DSC and thermogravimetric (TG) analyses were also carried out. The result indicates that a continuous process of dehydration, amorphization and recrystallization for MCP H2O in the solid state was easily evidenced via the thermal responsive IR spectral changes by using this simultaneous DSC-FTIR microspectroscopy. In the heating course, one mole of water was first dehydrated from the MCP H2O sample beyond 77 °C, was then quickly transformed to an amorphous form due to the appearance of weak broad IR bands, and continuously recrystallized from 148 °C by showing the sharp IR bands. This one-step novel simultaneous DSC-FTIR microspectroscopy might be available for studying the changes in the progressive processes of the thermal-dependent solid-state characterizations of drugs.

A Solid-State Dehydration Process in an Organic Material Associated with Substantial Hydrogen-Bond Reorganization, Investigated by Powder X-ray Diffraction

Solid tert-butylammonium acetate monohydrate undergoes a facile solid-state dehydration process under ambient conditions, in which single crystals of the monohydrate phase transform to a microcrystalline powder of an anhydrous product phase. The structural properties of the anhydrous phase have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement, allowing rationalization of the structural changes associated with the dehydration process. The dehydration process is associated with substantial reorganization of the hydrogen bonding arrangement, although one component of the hydrogen-bonding scheme is actually preserved in the transformation.

Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques

The extensively used antibacterial agent acrinol is known to form a monohydrate phase (H) on crystallization from water. We demonstrate here that acrinol also forms two anhydrous polymorphs, denoted form I (AI) and form II (AII). Polymorph AI is obtained directly on heating H, by a solid-state dehydration process, and polymorph AII is obtained subsequently from AI, by a polymorphic transformation. The crystal structures of AI and AII have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. From the structural properties of AI and AII, mechanistic aspects of the dehydration process and the polymorphic transformation have been established. From measurements of initial dissolution rates and enthalpies of dissolution, AII is assigned as the thermodynamically stable polymorph, with a monotropic relationship between AI and AII. The hydration properties of AI and AII differ significantly, with hydration of AI occurring at substantially lower relative humidity than AII.

Solid-State Dehydration of Uric Acid Dihydrate

Uric acid dihydrate (UAD) is a crystalline constituent present in a significant fraction of human renal precipitates. Using a combination of techniques including powder X-ray diffraction, hot-stage light microscopy, differential scanning calorimetry, and thermogravimetric analysis, the mechanism and kinetics of its irreversible dehydration to polycrystalline anhydrous uric acid (UA) is analyzed as a function of intrinsic sample parameters (e.g., crystal size, shape, structure) and environmental conditions (e.g., temperature and humidity). The highly anisotropic dehydration of UAD to UA is rationalized on the basis of its crystal structure and morphology, and appears to involve no other crystalline intermediate phases. Mechanistic models derived from both isothermal and nonisothermal kinetic data support a one-dimensional-phase boundary mechanism. Increasing relative humidity conditions were found to decrease the dehydration kinetics up to a point, after which a dissolution−recrystallization mechanism is e...

Facile methods to synthesize nanaosized iron oxide colloidal dispersion and its characterization

In this study, we develop two experimental procedures to synthesize a nanosized α-Fe 2O 3 colloidal suspension within a relatively short reaction time. In the first method, we use ferric chloride as the precursor, both NaOH and urea as the precipitant, and polyvinyl pyrrolidone (PVP) as the protecting agent; we find that by adding ferrous ion (Fe 2+), nanosized α-iron oxide colloids are formed in about 40 min. The ferrous ion accelerates the conversion of Fe(OH) 3 to α-Fe 2O 3, probably by helping with the dissolution of iron hydroxide and then its re-crystallization into iron oxide. In the second method, two thirds of the stoichiometric amount of NaOH is first used to precipitate iron hydroxide. It is then heated at boiling temperature in the presence of urea or sodium bicarbonate (NaHCO 3) to complete the transformation into hematite in less than an hour. The solution pH increases with time and the transformation from iron hydroxide to α-Fe 2O 3 probably takes place by the solid state transformation mechanism. The common point between urea and sodium bicarbonate is the generation of CO 2 during the reaction, which might play some role in helping with the solid state dehydration reaction.

A Solid-State Dehydration Process Associated with a Significant Change in the Topology of Dihydrogen Phosphate Chains, Established from Powder X-ray Diffraction

The anhydrous crystalline phase of chloroquine bis-(dihydrogen phosphate) is obtained by dehydration of the corresponding hydrate phase, but in common with many solid-state dehydration processes, the product is obtained as a polycrystalline powder, thus limiting the opportunity to carry out structural characterization using single crystal X-ray diffraction techniques. Instead, structure determination of the anhydrous phase has exploited the capabilities of modern powder X-ray diffraction techniques, employing the direct-space Genetic Algorithm technique for structure solution followed by Rietveld refinement. The results reveal that the dehydration process is associated with a significant change in the topology of hydrogen bonded chains of dihydrogen phosphate anions, arising from a change in the hydrogen bonding arrangement within the chains, together with a significant change in the conformation of the chloroquine cation.