Formate Dihydrate Research Articles

Solid-State NMR and X-ray Diffraction Study of Structure and Dynamics of Dihydrate and Anhydrous Form of Tyr-Ala-Phe

Tyr-d-Ala-Phe is a “message sequence” of naturally occurring opioid peptides, deltorphin I (Tyr-d-Ala-Phe-Asp-Val-Val-Gly-NH2), deltorphin II (Tyr-d-Ala-Phe-Glu-Val-Val-Gly-NH2), and dermorphin (Tyr-d-Ala-Phe-Gly-Tyr-Pro-Ser-NH2). Analogous heptapeptides containing l-alanine instead of d-alanine are not biologically active. In a previous paper (J. Phys. Chem. B 2004, 108 (14), 4535−4545), we reported X-ray and NMR data for Tyr-d-Ala-Phe. In the current report, we present structural studies of Tyr-Ala-Phe, a “false message sequence” of opioid peptides. It has been found that Tyr-Ala-Phe crystallizes in two forms, as anhydrate (Form I) and dihydrate (Form II). Crystal and molecular structure of both forms was established by means of low-temperature X-ray measurements. Form I is orthorhombic with space group P212121, while II is hexagonal with space group P65. Solid-state NMR was employed to study the structure and molecular dynamics of I and II. Analysis of cross-polarization buildup curves and 13C chemical...

Inhibition of the crystal growth and aggregation of calcium oxalate by elemental selenium nanoparticles

Chemical modulation of calcium oxalate (CaC 2O 4) crystals morphologies by elemental selenium nanoparticles (nanoSe 0) was investigated with scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), Fourier transform infrared spectrometry (FTIR), and X-ray diffraction (XRD) analysis. The coordination between nanoSe 0 and C 2O 4 2− had great effect on the formation of CaC 2O 4 crystals. NanoSe 0 inhibited the growth of calcium oxalate monohydrate (COM) crystals, prevented the aggregation of COM crystals and induced the formation of the spherical calcium oxalate dihydrate (COD) crystals containing selenium, which are the thermodynamically less stable phase and has a weaker affinity to the cell membranes than COM crystals. The inhibition of the crystal growth and aggregation of CaC 2O 4 crystals by nanoSe 0 displayed concentration effects.

Exploring the Formation of Multiple Layer Hydrates for a Complex Pharmaceutical Compound

The pharmaceutical compound A, 3-{2-oxo-3-[3-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)propyl]imidazolidin-1-yl}-3(S)-(6-methoxypyridin-3-yl)propionic acid, is known to exist in five different crystalline forms that differ in the hydration state ranging from the anhydrous desolvate over hemihydrate, dihydrate, and tetrahydrate forms to the pentahydrate. The formation of the higher hydrates and the concomitant lattice expansion leads to undesirable tablet cracking at higher humidities. In this work, particle-based simulation techniques are used to explore the hydrate formation of compound A as a function of humidity. It is found that a simulation strategy employing Monte Carlo simulations in the isobaric-isothermal and Gibbs ensembles and transferable force fields, which are not parametrized against any experimental data for compound A, is able to yield satisfactory crystal structures for the anhydrate and pentahydrate and to predict the existence of all five hydrates.

Mechanisms for Dehydration of Three Sodium Naproxen Hydrates

Sodium naproxen, a member of the class of nonsteroidal anti-inflammatory drugs (NSAID), exists in an anhydrous form and the following four hydrated ones: one monohydrate, two dehydrates, and one tetrahydrate. In the present work, the authors observed the isothermal dehydration of some of these hydrates by thermogravimetry at several temperatures. The rate of water removal from the crystal was used to determine the mechanism of dehydration in the solid state, by fitting results with selected expressions corresponding to the most common solid-state processes. The water loss was then evaluated according to Eyring’s equation, and both changes in activation enthalpy (ΔH*) and activation entropy (ΔS *) were estimated from rate constant values. Experiments made it possible to distinguish different dehydration mechanisms for these hydrate forms, and in particular, to discern the dehydration behavior of two different dihydrate forms, one obtained by crystallizing sodium naproxen from water (CSN) and the other obta...

Solubility Advantage of Pharmaceutical Cocrystals

Pharmaceutical cocrystals can improve solubility, dissolution, and bioavailability of poorly water soluble drugs. However, true cocrystal solubility is not readily measured for highly soluble cocrystals because they can transform to the most stable drug form in solution. The objectives of this study are to develop a method to estimate the cocrystal solubility in pure solvent and establish the influence of constituent drug and ligand (i.e., coformer) properties. Cocrystal solubility and solubility product were derived from transition concentration measurements where a solution is in equilibrium with solid drug and cocrystal. Transition concentrations and solubilities are reported for carbamazepine cocrystals in water, ethanol, isopropanol, and ethyl acetate. The aqueous solubility for seven carbamazepine cocrystals was estimated to be 2−152 times greater than the solubility of the stable carbamazepine dihydrate form. Cocrystal solubility is shown to be directly proportional to the solubility of constituent...

Peganine hydrochloride dihydrate an orally active antileishmanial agent

Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (±8.07)% against established VL in hamsters at a dose of 100 mg/kg b.wt.

Water sorption on composite “silica modified by calcium nitrate”

Composite SWS-8L was synthesized by impregnating a mesoporous silica KSK with a saturated aqueous solution of Ca(NO 3) 2. Its equilibrium with water vapor was studied by measuring sorption isobars and isosters at T = 30–150 °C. The water sorption increased up to 0.2–0.3 g/g due to the presence of the salt inside the silica pores. The water uptake was not a simple addition of those by the bulk salt and the silica, because the confined salt changed its properties. The isosteric sorption heat decreased from 52 to 47 kJ/mol when the water uptake increased from 0.07 to 0.23 g/g. The X-ray diffraction study revealed no formation of crystalline dihydrate in the confined state during the hydration process that can be caused by the dihydrate dissolution inside the pores. For approximation of the sorption equilibrium, a simple analytical equation based on the Polanyi principle of temperature invariance was suggested. Sorption kinetics was studied by the Isothermal Differential Step method at T = 50 and 70 °C and the pressure range 10–35 mbar. Confinement of calcium nitrate to the silica pores significantly hastened the sorption with respect to the bulk salt. The hydration of the confined salt was limited by the intraparticle water diffusion instead of intrinsic chemical transformation of the bulk salt. Comparison of the new composite adsorbent with those based on CaCl 2, MgSO 4 and LiBr confined to the same host matrix showed that SWS-8L can be envisaging further development for adsorptive air conditioning driven by low temperature heat.

Effect of supersaturation ratio and Khella extract on nucleation and morphology of kidney stones

Induction times in supersaturated calcium oxalate (CaOx)–the major component of most kidney stones–solutions were determined at 37°C using UV–vis spectrometry with and without Khella extract. The slope of the light absorbance measurement curve indicated the inhibition of calcium oxalate nucleation with Khella extract. The induction time was estimated from the time vs. absorbance curve. Khella seeds were obtained from two sources, one in Turkey and one in Egypt. High performance liquid chromatography (HPLC) results showed that only Turkish Khella extract contained khellin and visnagin that are believed to be the active components of the herb. Both extracts contained calcium, magnesium, and oxalate. It was found that both Khella extracts reduced the induction time at every supersaturation ratio.Using an equation that relates induction times and supersaturation ratios, free energy barrier, and critical nuclei radius were calculated. The results revealed that decrease of free energy barrier and critical nuclei radius as supersaturation ratio increased. In addition, the calculated surface energy of calcium oxalate crystals was decreased from 9.01 to 6.79 and 6.40mJ/m2 with Egyptian Khella extract and Turkish Khella extract, respectively. Scanning electron microscopy (SEM) photomicrographs showed that the control supersaturated CaOx solutions produced CaOx monohydrate (COM) crystals. With the addition of Khella extract, the resulting crystals were modified to calcium oxalate dihydrate (COD) form.

Depleted zinc: Properties, application, production

The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

Identification of monoclinic calcium pyrophosphate dihydrate and hydroxyapatite in human sclera using Raman microspectroscopy

Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.

Physico‐Chemical and Technological Properties of Sodium Naproxen Granules Prepared in a High‐Shear Mixer‐Granulator

In the present work, authors produced tablets of anhydrous sodium naproxen by wet granulation using a high‐shear mixer‐granulator. Drug hydrated to the tetrahydrated form, as observed by X‐ray powder diffractometry. After wet granulation, authors then performed two different drying procedures, obtaining granules of different water content and crystallographic characteristics. The first procedure dried granules in the high‐shear mixer‐granulator by applying vacuum at room temperature (batch A), while the second employed the same apparatus and time, under vacuum at 40°C (batch B). X‐ray powder diffractometry revealed that the sodium naproxen (SN) contained in batch A granules was a mixture of dihydrated and tetrahydrated forms (as demonstrated by the coexistence of peaks typical of both hydrated forms), while that of batch B granules was a mixture of monohydrated and tetrahydrated forms. This means that differences in drying procedures could lead to products of different crystallographic properties. The behavior under compression was evaluated, revealing that batch A offered the best tabletability and compressibility. These results make it possible to conclude that differences in the crystallographic properties and water content of SN are such that different hydration/drying processes can alter the drug crystal form and thus the tabletability of the resulting granules. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5263–5273, 2008

Kinetic Study of Formate Compounds Developed on Copper in the Presence of Formic Acid Vapor

“Ant-nest” corrosion is a specific type of premature failure of copper tubes used in air-conditioning units causing the loss of refrigerant liquid and consequent environmental pollution. It is known that attack requires the simultaneous presence of moisture, oxygen, and a corrodent, usually formic acid. This type of corrosion occurs in thin-walled copper pipes, especially when copper is deoxidized high residual phosphorus. A study has been made of the copper corrosion products formed by the action of formic acid vapor for exposure at 100% relative humidity and under thermal cycling. The corrosion-product layer was characterized using X-ray diffraction (XRD). The identified compounds were cuprite , copper hydroxide hydrate , copper hydroxyformate [Cu(OH)(HCOO)], anhydrous copper formate , copper formate dihydrate , and copper formate tetrahydrate . Tentatively, the latter phase is described in relation with ant-nest corrosion in this paper. A kinetic study of the solid crystalline phases formed on copper has been performed using XRD patterns and the compound ratio has been compared over exposure time.

Spectroscopic Monitoring of Carbamazepine Crystallization and Phase Transformation in Ethanol−Water Solution

The crystallization mechanism of anhydrate/hydrate has to be understood in order to control the hydration state of an active pharmaceutical ingredient. In the present work, the formation of the anhydrous (CBZA) and dihydrate (CBZH) form of carbamazepine (CBZ) in ethanol−water solutions was studied by simultaneous monitoring of both the anhydrate/hydrate phase of the crystals and the CBZ concentration in the mother liquor with the Raman immersion probe. Two different cooling strategies and the effect of one surfactant were studied. The information obtained from the Raman spectroscopy indicated that the thermodynamic factor was dominated in determining the anhydrate/hydrate form of the crystals in the studied system. The thermodynamically stable form was obtained in all studied crystallization conditions. The presence of a surfactant additive showed a slight promotion effect only on the phase transformation of CBZA to CBZH. The results obtained in the present work lead to improved understanding of the forma...

Structural studies in solution and in the solid state on the zinc chelate of 2-hydroxy-(4-methylthio)butanoic acid, an effective mineral supplement in animal feeding

The bis-chelate complex of Zn 2+ with 2-hydroxy-(4-methylthio)butanoate (MHA -H the anion derived from the so-called methionine hydroxy-analogue, MHA) is an effective, bioavailable mineral supplement for animal feeding. It can be obtained in two solid forms: the anhydrous [Zn(OC(O)CH 2CH(OH)CH 2CH 2SCH 3) 2] and the corresponding dihydrate species, both well distinguishable by IR spectroscopy and powder X-ray diffraction. The crystal and molecular structure of the dihydrate form has been solved by single-crystal X-ray diffraction. It consists of dinuclear bis-chelate species with a bridging carboxylate group, both zinc atoms displaying hexacoordination involving all the hydroxyl and carboxyl groups from the four MHA -H anions and three oxygens from different water molecules. The fourth water molecule does not participate in coordination. Therefore, the dihydrate complex must be formulated as [Zn 2(OC(O)CH 2CH(OH)CH 2CH 2SCH 3) 4(H 2O) 3] · H 2O ( 1). A molecular computational analysis has been carried out by density functional theory (DFT) on three possible MHA -H zinc chelates, i.e. the dinuclear bis-chelate observed in the solid state, the mononuclear bis-chelate diaquo-complex, and the monochelate tetraaquo-complex. Calculations have suggested that between the dinuclear and mononuclear bis-chelates, the preferred form in aqueous solution may be the second one. Moreover, both 1H (chemical shifts and relaxation rates) and 13C NMR data provide further evidence for the formation of Zn/MHA -H chelates in solution.

Influence of crystal hydration on the mechanical properties of sodium naproxen

The aim of this work is to establish a correlation between water uptake by anhydrous sodium naproxen (ASN) at two different relative humidities and modifications in tableting and densification behaviour under hydration. Water uptake was evaluated at different relative humidities. Models for the hydration kinetics of ASN at 55% and 86%, corresponding to the formation of the dihydrated and tetrahydrated forms, respectively, were evaluated assuming Eyring’s dependence on temperature. Tabletability, compressibility, compactibility, and densification behaviour were determined using an instrumented single punch tablet machine. Kinetic data are consistent with a model where water molecules enter the crystal preferentially along hydrophilic tunnels existing in the crystal structure and corresponding to the propionate side chain. Water inclusion perturbs the crystallographic structure, causing slight structural changes according to the amount and associated to an increase in entropy. The interposition of water molecules between sodium naproxen molecules weakens intermolecular bonds, and these sites can behave like sliding planes under compression. Such structural changes may explain the improved compression behaviour and modified densification propensity mechanism. Kinetic data describing the water hydration mechanism of ASN explain in an original way the improved tableting and densification properties under hydration.

Thermodynamic properties and thermal stability of the synthetic zinc formate dihydrate

Zinc formate dihydrate has been synthesized and characterized by powder X-ray diffraction, elemental analysis, FTIR spectra and thermal analysis. The molar heat capacity of the coordination compound was measured by a temperature modulated differential scanning calorimetry (TMDSC) over the temperature range from 200 to 330 K for the first time. The thermodynamic parameters such as entropy and enthalpy vs. 298.15 K based on the above molar heat capacity were calculated. The thermal decomposition characteristics of this compound were investigated by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). TG curve showed that the thermal decomposition occurred in two stages. The first step was the dehydration process of the coordination compound, and the second step corresponded to the decomposition of the anhydrous zinc formate. The apparent activation energy of the dehydration step of the compound was calculated by the Kissinger method using experimental data of TG analysis. There are three sharply endothermic peaks in the temperature range from 300 to 650 K in DSC curve.

Effect of HPMC on solubility and dissolution of carbamazepine form III in simulated gastrointestinal fluids

The effect of HPMC on solubility and dissolution of carbamazepine form III (CBZ) was investigated in 50% w/w of CBZ form III in HPMC solid dispersion and physical mixture. Powdered samples of CBZ form III, physical mixture, and solid dispersion were characterized for thermal behavior (DSC), crystallinity (PXRD), and compatibility (FT-IR). Solubility and dissolution studies were carried out in different simulated gastrointestinal fluids and de-ionized water. Solubility studies in simulated gastric fluid (SGF) revealed that acidic pH favors formation of CBZ dihydrate.Triton X 100 in blank fast-state simulated gastric fluid (FaSSGF) prevents the formation of CBZ dihydrate in acidic pH. A maximum solubility of 268.77 μg/mL was achieved with fed-state simulated intestinal fluid (FeSSIF). Correlation between solubility and pH could not be established. Both solubility and dissolution studies revealed that HPMC had a profound effect of enhancement of solubility and dissolution of CBZ form III in both physical mixtures and solid dispersions. HPMC prevents the formation of CBZ dihydrate and thereby improves the solubility and dissolution. This was further correlated with results obtained from DSC and XRD. There was no drastic difference in solubility and dissolution of CBZ form III with different media. It was observed that there was no existing relationship between solubility and dissolution of CBZ form III in different media.

Synchrotron X‐Ray Charge‐Density Study of Coordination Polymer [Mn(HCOO)2(H2O)2]∞

AbstractThree high‐quality single‐crystal X‐ray diffraction data sets have been measured under very different conditions on a structurally simple, but magnetically complex, coordination polymer, [Mn(HCOO)2(H2O)2]∞(1). The first data set is a conventional 100(2) K MoKαdata set, the second is a very high resolution 100(2) K data set measured on a second‐generation synchrotron source, while the third data set was measured with a tiny crystal on a high brilliance third‐generation synchrotron source at 16(2) K. Furthermore, the magnetic susceptibility (χ) and the heat capacity (Cp) have been measured from 2 to 300 K on pressed powder. The charge density of1was determined from multipole modeling of the experimental structure factors, and overall there is good agreement between the densities obtained separately from the three data sets. When considering the fine density features, the two 100 K data sets agree well with each other, but show small differences to the 16 K data set. Comparison with ab initio theory suggests that the 16 K APS data set provides the most accurate density. Topological analysis of the metal–ligand bonding, experimental 3d orbital populations on the Mn atoms, and Bader atomic charges indicate quite ionic, high‐spin metal atoms. This picture is supported by the effective moment estimated from the magnetization measurements (5.840(2) μB), but it is at variance with earlier spin density measurements from polarized neutron diffraction. The magnetic ordering originates from superexchange involving covalent interactions with the ligands, and non‐ionic effects are observed in the static deformation density maps as well as in plots of the valence shell charge concentrations. Overall, the present study provides a benchmark charge density that can be used in comparison with future metal formate dihydrate charge densities.

Effect of Polymer Additives on the Transformation of BMS-566394 Anhydrate to the Dihydrate Form

To investigate the effect of polymer additives on the transformation of BMS-566394 anhydrate to the dihydrate form and to propose the possible mechanisms for inhibition of conversion of the anhydrate to the dihydrate form. The conversion of anhydrate to dihydrate was monitored using differential scanning calorimetry, powder X-ray diffraction and polarized light microscopy. Solubility and intrinsic dissolution studies were performed on anhydrate and dihydrate. IR and NMR spectroscopy were used to probe the molecular interactions between BMS-566394 and cellulose ether polymers. The anhydrate form of BMS-566394 was readily transformed into the more stable dihydrate form in aqueous suspension. The kinetic solubility and intrinsic dissolution rate of the anhydrate were ca. fourfold that of the dihydrate. Addition of cellulose ether polymers (HPC, HPMC, MC) inhibited anhydrate to dihydrate transformation in aqueous suspensions. Hydrogen bonding interaction between the polar groups of the drug and polymers was inferred from infrared spectroscopy. Solution NMR also indicated a hydrophobic interaction between the drug and polymer backbone. The anhydrate form of BMS-566394 is stabilized in the presence of cellulose ether polymers. Spectroscopic evidence is offered to postulate a molecular interaction between drug and polymers.

Preparation and Dissolution Profiles of the Amorphous, Dihydrated Crystalline, and Anhydrous Crystalline Forms of Paclitaxel

The selection of pharmaceutical polymorphisms in the final production step is very important in terms of product recovery, properties, and storage. The amorphous, dihydrated crystalline, and anhydrous crystalline forms of paclitaxel were prepared using precipitation, spray drying, and colloid formation methods. These methods were found to be highly efficient and convenient, giving high recovery, short processing time, and good stability, as compared with conventional methods such as freeze drying, evaporation, recrystallization, and melting. The polymorphic natures of the resulting paclitaxel samples were confirmed by XRPD, IR, TGA, DSC, and SEM. The dissolution rates of the paclitaxel samples were studied in pharmaceutical solvents, which included cotton seed oil, corn oil, tricaprylin, and tributyrin. For each solvent, all of the amorphous paclitaxel samples showed much higher dissolution rates than the dihydrated crystalline, anhydrous crystalline, and commercial forms, and can be used for clinical applications that demand improvements in drug delivery.