Monohydrate Phase Research Articles

Dehydration and rehydration of Zn-hydroxy sulfate minerals with interrupted decorated hydroxide sheets

The dehydration-rehydration processes of three Zn-hydroxy sulfate minerals with interrupted decorated sheet structures – osakaite, gordaite and Ca-gordaite were investigated. The obtained products and processes were characterized by DTA-TG-MS, in situ and ex situ PXRD and FTIR.In osakaite structure the two different positions of water molecules cause different ways of dehydration. The derivation of each interlayer molecule results in the formation of discrete phases, with 4, 3 and 1 H2O, without any evidence for dihydrate formation. The process was conducted by both heating and adsorption. The rehydration of these metaphases proceeds reciprocally to the dehydration with relatively high rate at middle and high RH values. The derivation of water molecules from the Zn tetrahedron occurs only on heating. The derivation of only half of the apical molecules was observed. The rehydration of formed hemihydrate metaphase proceeds very slowly even at high RH values. The fully dehydrated phase thus proved to be impossible to form. Structural schemes of monohydrate and hemihydrate phases were proposed. In osakaite structure type all changes occur on the surface of the hydroxide layer, preserving its electrically neutral character, with further possible implications for facilitating intercalation of polar molecules.The negatively charged surface of gordaite hydroxide layer, caused by the occupation of apical position of Zn tetrahedra by Cl− determine dehydration behavior, similar to that of montmorillonite and vermiculite structures. On heating, gordaite and Ca-gordaite form three and two pillared structures with different sizes of interlayer space and different amount of water molecules for each phase. The rate of dehydration and/or rehydration and particular quantity of derived water molecules is controlled by the interlayer cations. In accordance with the high ionic potential of calcium, the dehydration of Ca-gordaite occurs only on heating and the rehydration proceeds at very low RH conditions. To the contrary, the much lower ionic potential of sodium causes the formation of dehydrated gordaite phases by both heating and by adsorption. Similarly to the montmorillonite and vermiculite – these two gordaite minerals can be expected to be used for both cation exchange for interlayer cations and anionic exchange of apical Cl−anion.

Guanine Crystallization in Aqueous Solutions Enables Control over Crystal Size and Polymorphism

Anhydrous guanine crystals are among the most widespread organic crystals used by organisms to produce structural colors. The main advantage of guanine is its exceptionally high refractive index in the reflecting direction (∼1.8). For the same reason, guanine is a promising candidate material for a variety of different optical applications. Crystallization of guanine is challenging and usually involves using polar aprotic organic solvents such as dimethyl sulfoxide (DMSO). Here, we show that the crystallization of guanine from aqueous solutions is possible under conditions that provide control over crystal polymorphism and size. Using this approach we were able produce large crystals of the elusive guanine monohydrate phase. We were also able to rationalize the formation of the different phases obtained as a function of which tautomer of guanine is stable in solutions of varying pH.

Understanding the Solid-State Hydration Behavior of a Common Amino Acid: Identification, Structural Characterization, and Hydration/Dehydration Processes of New Hydrate Phases of l-Lysine

The crystal structure of l-lysine was reported very recently and represented the final member of the set of 20 directly encoded proteinogenic amino acids to have a crystal structure of the enantiomerically pure form determined. Under ambient conditions, l-lysine has a strong propensity to undergo hydration by incorporation of water into the crystal structure, and dehydration under rigorously dry conditions is required to obtain anhydrous l-lysine. In the present paper, we explore the hydration of l-lysine, which has led to the identification and characterization of a hemihydrate phase and a monohydrate phase. As the hydration processes give rise to microcrystalline powder samples of the hydrate phases, powder X-ray diffraction has been exploited for crystal structure determination of both l-lysine hemihydrate and l-lysine monohydrate. The conditions for interconversion between anhydrous l-lysine and the two hydrate phases have been investigated by dynamic vapor sorption measurements, leading to an underst...

Investigation of the Interaction between Perovskite Films with Moisture via in Situ Electrical Resistance Measurement.

Organometal halide perovskites have recently emerged as outstanding semiconductors for solid-state optoelectronic devices. Their sensitivity to moisture is one of the biggest barriers to commercialization. In order to identify the effect of moisture in the degradation process, here we combined the in situ electrical resistance measurement with time-resolved X-ray diffraction analysis to investigate the interaction of CH3NH3PbI(3-x)Cl(x) perovskite films with moisture. Upon short-time exposure, the resistance of the perovskite films decreased and it could be fully recovered, which were ascribed to a mere chemisorption of water molecules, followed by the reversible hydration into CH3NH3PbI(3-x)Cl(x)·H2O. Upon long-time exposure, however, the resistance became irreversible due to the decomposition into PbI2. The results demonstrated the formation of monohydrated intermediate phase when the perovskites interacted with moisture. The role of moisture in accelerating the thermal degradation at 85 °C was also demonstrated. Furthermore, our study suggested that the perovskite films with fewer defects may be more inherently resistant to moisture.

Studies of phase transitions in the aripiprazole solid dosage form

Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10mg and 30mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify® 10mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III.

Structural Diversity in 1,3-Bis(m-cyanophenyl)urea

Hydrogen bonding between 1,3-bis ureas is a commonly used motif in the assembly of supramolecular structures such as gels, capsules and crystals. The title compound, 1,3-bis(m-cyanophenyl)urea (mCyPU), has previously been shown to crystallize in both an anhydrous and monohydrate phase (α and H–I). An expanded search for polymorphs and cocrystals of mCyPU revealed a much greater diversity of solid forms including three additional polymorphs (β, δ, e), a second hydrate (H–II) and two cocrystal phases with dimethyl sulfoxide and triphenylphosphine oxide. Analysis of the single crystal structures obtained in this study shows that the typical 1-dimensional H-bonding between 1,3-bis urea groups is disrupted by the presence of other H-bond acceptors including cyano, water, sulfoxide and phosphine oxide functionalities. Re-examination of α-mCyPU additionally showed both blade and plate-like morphologies could be obtained from different growth solvents, with crystals of the latter morphology exhibiting a grain bou...

Temperature- and moisture-dependent powder X-ray diffraction studies of kanemite (NaSi2O4(OH)·3H2O)

AbstractThe high-temperature- and moisture-dependent behaviour of synthetic kanemite (NaSi2O4(OH)·3H2O orSKS-10) has been studied byin situpowder X-ray diffraction. Heating experiments in the range between ambient temperatures and 250°C confirm earlier investigations that the dehydration of kanemite occurs in two steps. According to our results the two different reactions start at ∼30 and 75°C. The dehydration products have the following compositions: NaSi2O4(OH)·H2O (monohydrate) and NaSi2O4(OH), respectively. The crystal structures of both phases have been solved at ambient conditionsab initiofrom laboratory powder diffraction data using samples that have been carefully dehydrated at 60 and 150°C, respectively, and refined subsequently by the Rietveld method. Basic crystallographic data are as follows: NaSi2O4(OH)·H2O: orthorhombic, space groupPna21,a= 7.2019(1),b= 15.3252(2),c= 4.8869(1) Å,V= 539.37(1) Å3,Z= 4; NaSi2O4(OH): monoclinic, space groupP21,a= 6.3873(1),b= 4.8876(1),c= 7.1936(1) Å, β = 93.36(1)°,V= 224.19(1) Å3,Z= 2. Both compounds belong to the group of single-layer silicates based on Si2O4(OH) sheets. The sodium cations are located between the tetrahedral sheets and are surrounded by oxygen atoms from silicate anions and/or water molecules. Depending on the dehydration step the coordination numbers of the alkali ions vary between six (kanemite) and five (NaSi2O4(OH)). Kanemite and its two dehydration products show structural similarities which are discussed in detail. Moisture-dependent diffraction studies at ambient temperatures indicate that kanemite is stable between 10% and at least 90% relative humidity. Below the lower threshold a transformation to the monohydrate phase was observed. Dehydration and rehydration as a function of humidity is reversible. However, this process is combined with a significant loss of crystallinity of the samples.

Crystal Chemistry of the Antibiotic Doripenem

Doripenem, an ultrabroad spectrum-injectable antibiotic belonging to the wide class of carbapenem beta-lactams, is commonly marketed as powders of a pure monohydrate phase. Here, we have selectively prepared another hydrated phase (a dihydrate) and determined the crystal structure of both forms by state-of-the art powder diffraction methods. Both phases crystallize in the monoclinic P21 space group, and, to some extent, are structurally related. Moreover, by using variable temperature diffractometric analyses, we also discovered a crystalline anhydrous form of doripenem, the structure of which (with two crystallographically independent molecules in the monoclinic P21 space group) remains so far unknown. The thermal interconversion among these phases was further studied by thermogravimetry, differential scanning calorimetry, and thermodiffractometric analyses, and their (metric or stereochemical) mutual relations fully analyzed. The complete structural characterization of the two hydrated phases allows the use of accurate whole pattern profile-fitting procedures for quantitative analyses of these drugs in polycrystalline, or even amorphous, matrices, opening the way to industrial process control and legal protection. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3641-3647, 2014.

Structure of the calcium pyrophosphate monohydrate phase (Ca2P2O7·H2O): towards understanding the dehydration process in calcium pyrophosphate hydrates.

Calcium pyrophosphate hydrate (CPP, Ca(2)P(2)O(7) · nH2O) and calcium orthophosphate compounds (including apatite, octacalcium phosphate etc.) are among the most prevalent pathological calcifications in joints. Even though only two dihydrated forms of CPP (CPPD) have been detected in vivo (monoclinic and triclinic CPPD), investigations of other hydrated forms such as tetrahydrated or amorphous CPP are relevant to a further understanding of the physicochemistry of those phases of biological interest. The synthesis of single crystals of calcium pyrophosphate monohydrate (CPPM; Ca(2)P(2)O(7) · H2O) by diffusion in silica gel at ambient temperature and the structural analysis of this phase are reported in this paper. Complementarily, data from synchrotron X-ray diffraction on a CPPM powder sample have been fitted to the crystal parameters. Finally, the relationship between the resolved structure for the CPPM phase and the structure of the tetrahydrated calcium pyrophosphate β phase (CPPT-β) is discussed.

Parametric Rietveld refinement applied to dehydration of sodium naproxen

The identification of the hydration and dehydration transformations of drugs is vital to establish stable pharmaceutical components. Our aim is to monitor the kinetics of hydration and dehydration processes in pharmaceutical solids, and to relate these to the molecular-level crystal structures. One of the primary tools to achieve this is parametric Rietveld refinement. The dehydration of two dihydrate polymorphs of the non-steroidal anti-inflammatory drug (NSAID) sodium naproxen was monitored using synchrotron powder X-ray diffraction measurements at Beamline I711, MAX IV Laboratory, Lund University. Diffraction patterns were measured in the range 300-400 K at 1 K increments. Both polymorphs dehydrate to form identical monohydrate then anhydrous phases. Independent Rietveld refinements were initially performed for each unique phase in order to establish initial values for the parametric refinement. The refinements were performed using TOPAS-Academic [1]. The structures are molecular and both dihydrate polymorphs display pseudosymmetry, thereby requiring an extensive set of restraints. One of the key advantages of the parametric Rietveld refinement is the possibility to introduce algebraic equations that describe the evolution of various parameters [2]. The kinetics of the dehydration processes were monitored using a sigmoid function applied to the scale factors of the various phases (see Figure). The evolution of the unit-cell parameters and atomic displacement parameters were also treated parametrically, and the influence of using multiple coordinate sets (one model per temperature) or a single common coordinate set for each phase was examined. One dihydrate polymorph shows a smooth and continuous transition to the monohydrate, whereas the other polymorph shows an abrupt transition. These differences are linked to the existence of topotactic or non-topotactic chemical transformations between the dihydrate polymorphs and the monohydrate phase.

In situ monitoring of hydration and dehydration in pharmaceutical solids

This talk will describe a multi-technique study of hydration and dehydration in pharmaceutical solids, using sodium naproxen as a case study. The aim of the work is to establish molecular-level structural understanding of the chemical changes that take place in the solid state as a function of temperature and relative humidity. Dynamic vapour sorption (DVS) analysis on the anhydrous compound carried out as a function of temperature provides a preliminary overview of the solid-form landscape and identifies static conditions to obtain four different hydrate forms [1]. Differences in the sorption and desorption cycles indicates the existence of a polymorphic dihydrate, and the two polymorphs show significant differences in their dehydration behaviour. Crystal structures are established for all phases in the system using either single-crystal or powder X-ray diffraction data, supplemented by dispersion-corrected density functional theory (DFT-D) calculations. The hydration and dehydration processes are monitored by powder X-ray diffraction (PXRD), as a function of relative humidity and temperature, and by variable-temperature solid-state 13C and 23Na NMR. Synchrotron PXRD is applied to the two dihydrate polymorphs to monitor the dehydration processes in approximately real time. The kinetic and structural details of dehydration are established by applying parametric Rietveld refinement [2] to the synchrotron data. This approach adds a structural picture to the kinetic processes. The PXRD studies indicate an essentially continuous dehydration pathway from one of the dihydrate polymorphs to the monohydrate, but a stepped dehydration pathway for the other dihydrate polymorph. The different mechanisms are linked to different degrees of structural similarity, and in particular to the existence of topotactic or non-topotactic transformations between the dihydrate polymorphs and the unique monohydrate and anhydrate phases.

Crystal growth of cholesterol in hydrogels and its characterization

In this work, we report the crystallization of cholesterol in ethanol solution and in three different hydrogel media: tetramethyl orthosilane, sodium metasilicate, and poly(vinyl)alcohol, whose structures are similar to the gel-like polymer structure of mucin, which is found in the mucus present in bile stone formation. The monohydrated triclinic phase was identified in all the samples by means of X-ray powder diffraction. The characteristic polymorphic crystalline transition of the anhydrous cholesterol was detected by differential thermal analysis and modulated differential scanning calorimetry only in crystals grown in ethanol, sodium silicate, and tetramethyl orthosilane. Finally, hysteresis of the phase transition temperature was measured by modulated differential scanning calorimetry in crystals grown in ethanol. The biological implications of the crystallization of cholesterol for bile stones formation are discussed in the last part of this contribution.

Assessing the Role of Water on the Electronic Structure and Vibrational Spectra of Monohydrated l-Aspartic Acid Crystals

In this work, we compare the calculated electronic and vibrational properties (infrared and Raman spectra) of anhydrous and monohydrated l-aspartic acid crystals to unveil the role of water in the later. This is accomplished through density functional theory (DFT) simulations within the Tkatchenko and Scheffler dispersion corrected generalized gradient approximation (GGA+TS). Both crystals are shown to have indirect band gaps and the simulations predict that water has a small effect on the Kohn–Sham band gap value (60 meV). Δ-sol corrected gaps, in contrast, exhibited a larger difference between the anhydrous and monohydrated crystals (main gap 0.30 eV larger for the latter). The conduction bands of the monohydrated species are much flatter because of structural changes produced by the presence of water, which leads to very large electron effective masses. However, the hole effective mass along the stacking direction of water molecules in the GGA+TS optimized monohydrated crystal is smaller than in other directions, suggesting that water stacking can improve on hole transport in similar bioorganic systems. These effects highlight the complex role of water on the carrier transport properties in monohydrated l-aspartic acid crystals, which is in contrast with the general belief that water simply increases the electrical conductance in molecular crystals. Finally, the calculated infrared and Raman spectra of the monohydrated phase exhibit molecular water vibrational signatures as well as water related peak shifts of as much as 100 cm–1 in comparison to those of the anhydrous structure. Remarkable water related Raman intensity peaks were obtained for the monohydrated crystal in the wavenumber ranges between 600 and 1000 cm–1 and between 2350 and 3450 cm–1, while for the infrared spectrum, a set of water absorption bands can be clearly identified in the 1550–1750 and 2800–3400 cm–1 wavenumber intervals.

Salt Forms of Amides: Protonation and Polymorphism of Carbamazepine and Cytenamide

In situ generation of HCl or HBr in alcohol leads to O-protonation of the amide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the only product isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.

Expanding the Solid-State Landscape of l-Phenylalanine: Discovery of Polymorphism and New Hydrate Phases, with Rationalization of Hydration/Dehydration Processes

To date, only one crystal structure of l-phenylalanine has been reported, with no confirmed report of polymorphism of this material. In the present work, we report the discovery of a new polymorph of l-phenylalanine, with the structural properties determined directly from powder X-ray diffraction data. The new polymorph of l-phenylalanine is stable only under rigorously dry conditions. In addition, two new solid hydrate phases of l-phenylalanine have been discovered: a monohydrate and a hemihydrate. The hemihydrate is susceptible to partial water deficiency. The crystal structures of the monohydrate and hemihydrate phases have also been determined directly from powder X-ray diffraction data. On the basis of results from dynamic vapor sorption and other experiments, we demonstrate that the three new solid forms are readily interconvertible as a function of relative humidity.

Reversible Switching from Antiferro- to Ferromagnetic Behavior by Solvent-Mediated, Thermally-Induced Phase Transitions in a Trimorphic MOF-Based Magnetic Sponge System

Hydrothermal reactions of copper(II) acetate, tetrazolate-5-carboxylate (tzc), and the neutral N-donor spacer ligand 1,3-di(4-pyridyl)propane (dpp) lead in a single reaction vial to the simultaneous formation of three different single-crystalline solvates [Cu(tzc)(dpp)]n·0.5C6H14·0.5H2O (1), [Cu(tzc)(dpp)]n·4.5H2O (2), and [Cu(tzc)(dpp)]n·1.25C6H14 (3). All three structures were characterized by single crystal X-ray diffraction. None of these solvates can be prepared as phase-pure bulk materials, but reaction conditions similar to those used for single crystal synthesis yield a phase-pure polycrystalline bulk material of an additional forth solvate phase [Cu(tzc)(dpp)]n·2H2O (4). Investigations of its thermal properties by in situ temperature-dependent synchrotron-based powder diffraction experiments have shown interesting phase transitions upon heating in a helium stream. Initially, the precursor dihydrate 4 transforms to an anhydrous phase [Cu(tzc)(dpp)]n (6I) via the intermediate monohydrate phase [Cu(tzc)(dpp)]n·H2O (5). Upon further heating, phase 6I transforms to a new anhydrous polymorph 6II, which transforms upon cooling to a further new phase 6III. Thermogravimetric measurements performed in tandem with differential scanning calorimetry as well as infrared spectroscopic investigations are in agreement with these findings. The de/resolvation behavior is accompanied by a dramatic change in their magnetic properties: The dihydrate phase shows antiferromagnetic exchange interactions, whereas ferromagnetic properties are observed for the trimorphic anhydrate system. This magnetic sponge-like behavior can be reversibly cycled upon de/resolvation of the material.

Mechanism of Dehydration–Hydration Processes of Lisinopril Dihydrate Investigated by ab Initio Powder X-ray Diffraction Analysis

Lisinopril is extensively used as an ethical anti-hypertensive drug in its dihydrate crystalline phase, where this phase undergoes dehydration to the metastable monohydrate and anhydrous phases upon being heated. The mechanistic aspects of this two-step dehydration process are successfully established from their crystal structures, determined for the first time by ab initio powder X-ray diffraction (PXRD) analysis. Furthermore, the hydration process of the anhydrous phase was investigated by humidity-controlled PXRD and dynamic vapor sorption. Although the dehydration process of the dihydrate phase proceeded in two steps via the metastable monohydrate phase, the hydration process from the anhydrous phase to the dihydrate phase proceeded in a single step. The mechanisms of these different pathways for the dehydration and hydration processes were also established from the crystal structures.

Importance of Accurate Spectral Simulations for the Analysis of Terahertz Spectra: Citric Acid Anhydrate and Monohydrate

The terahertz (THz) spectra of crystalline solids are typically uniquely sensitive to the molecular packing configurations, allowing for the detection of polymorphs and hydrates by THz spectroscopic techniques. It is possible, however, that coincident absorptions may be observed between related crystal forms, in which case careful assessment of the lattice vibrations of each system must be performed. Presented here is a THz spectroscopic investigation of citric acid in its anhydrous and monohydrate phases. Remarkably similar features were observed in the THz spectra of both systems, requiring the accurate calculation of the low-frequency vibrational modes by solid-state density functional theory to determine the origins of these spectral features. The results of the simulations demonstrate the necessity of reliable and rigorous methods for THz vibrational modes to ensure the proper evaluation of the THz spectra of molecular solids.

Thermal analysis: A further step in characterizing solid forms obtained by screening crystallization of an API

Phase and habit selection is a very important step in the early stages of pharmaceutical development of new APIs. In this paper, we show how observation, diffraction and thermal analysis are complementary methods of solid habit and phase characterization. At the end of phase screening of an API several habits and phases can be discriminated by microscopy, XRPD or Raman spectroscopy. Using thermal methods here allows us to separate the 12 phases discriminated by XRPD into: anhydrous, monohydrate, organic monosolvate and heterosolvate phases.

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.