Tuning Mechanical Properties of Pharmaceutical Crystals with Multicomponent Crystals: Voriconazole as a Case Study

Crystals of voriconazole, an antifungal drug, are soft in nature, and this is disadvantageous during compaction studies where pressure is applied on the solid. Crystal engineering is used to make cocrystals and salts with modified mechanical properties (e.g., hardness). Cocrystals with biologically safe coformers such as fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with hydrochloric acid and oxalic acid are prepared through solvent assisted grinding. The presence (salt) or absence (cocrystal) of proton transfer in these multicomponent crystals is unambiguously confirmed with single crystal X-ray diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and 1:1). The nanoindentation technique was applied on single crystals of the salts and cocrystals. The salts exhibit better hardness than the drug and cocrystals in the order salts drug cocrystals. The molecular origin of this mechanical modulation is explained on the basis of slip planes in the crystal structure and relative orientations of the molecules with respect to the nanoindentation direction. The hydrochloride salt is the hardest solid in this family. This may be useful for tableting of the drug during formulation and in drug development.

Effect of Pt doping on the gas sensing properties of porous chromium oxide films through a kinetic response analysis approach

The effect of doping trace amounts of noblemetals (Pt) on the gas sensing properties of chromium oxide thin films, is studied. The sensors are fabricated by depositing chromium oxide films on a glass substrate using a modified spray pyrolysis technique and characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. The films are porous and nanocrystalline with an average crystallite size of similar to 30 nm. The typical p-type conductivity arises due to the presence of Cr vacancies, formed as a result of Cr non-stoichiometry, which is found to vary upon Pt doping. In order to analyze the effect of doping on the gas sensing properties, we have adopted a kinetic response analysis approach, which is based on Langmuir Adsorption isotherm (LA) theory. The sensor response is analyzed with equations obtained from LA theory and time constants as well as energies of adsorption-desorption are evaluated. It is seen that, Pt doping lowers the Schottky barrier height of the metal oxide semiconductor sensor from 222 meV to 172 meV. Subsequently the reduction in adsorption and desorption energies led to enhancement in sensor response and improvement in the kinetics of the sensor response i.e. the response time as well as recovery times of the sensor.

Do carboximide-carboxylic acid combinations form co-crystals? The role of hydroxyl substitution on the formation of co-crystals and eutectics

Carboxylic acids, amides and imides are key organic systems which provide understanding of molecular recognition and binding phenomena important in biological and pharmaceutical settings. In this context, studies of their mutual interactions and compatibility through co-crystallization may pave the way for greater understanding and new applications of their combinations. Extensive co-crystallization studies are available for carboxylic acid/amide combinations, but only a few examples of carboxylic acid/imide co-crystals are currently observed in the literature. The non-formation of co-crystals for carboxylic acid/imide combinations has previously been rationalized, based on steric and computed stability factors. In the light of the growing awareness of eutectic mixtures as an alternative outcome in co-crystallization experiments, the nature of various benzoic acid/cyclic imide combinations is established in this paper. Since an additional functional group can provide sites for new intermolecular interactions and, potentially, promote supramolecular growth into a co-crystal, benzoic acids decorated with one or more hydroxyl groups have been systematically screened for co-crystallization with one unsaturated and two saturated cyclic imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic carboximide co-crystals is reported, including polymorphic and variable stoichiometry co-crystals. In the cases where co-crystals did not form, the combinations are shown invariably to result in eutectics. The presence or absence and geometric disposition of hydroxyl functionality on benzoic acid is thus found to drive the formation of co- crystals or eutectics for the studied carboxylic acid/imide combinations.

Computational modeling of reactive hot pressing of zirconium carbide

A model of reactive hot pressing of zirconium carbide (ZrCx, 0.5 < x < 1) has been constructed that incorporates four processes that occur in parallel: creep of zirconium (Zr), reaction of Zr and carbon (C), increase in volume fraction of hard phase with progressive reaction that reduces the creep of Zr and, finally, de-densification associated with volume reduction during reaction. The reasonable agreement of the model with experimental results verifies that plastic deformation of Zr is the main factor that is responsible for the low-temperature reactive densification of ZrC and that ZrC may be treated as a rigid inclusion that contributes little to densification. It predicts that densification is impaired by increasing carbon stoichiometry due to the increasing amount of starting hard phase and the greater contraction upon reaction. Additionally, the model predicts that mixtures of Zr and ZrC should show equal or better densification than Zr and C mixtures.

The X-ray photoelectron spectroscopy and high-temperature structural studies of Zn1-xNixO/NiO two-phase composites

Detailed investigation of the chemical states and local atomic environment of Ni and Zn in the two-phase composites of Zn1-xNixO/NiO was reported. The X-ray photoelectron spectra of both Ni-2p and Zn-2p revealed the existence of a doublet with spin-orbit splitting approximate to 17.9 and 23.2eV, respectively confirming the divalent oxidation state of both Ni and Zn. However, the samples fabricated under oxygen-rich conditions exhibit significant difference in the binding energy approximate to 18.75eV between the 2p3/2 and 2p1/2 states of Ni. The shift in the satellite peaks of Ni-2p with increasing the Ni composition x within the Zn1-xNixO/NiO matrix signifies the attenuation of nonlocal screening because of reduced site occupancy of two adjacent Zn ions. The temperature dependence of X-ray diffraction analysis reveals a large distortion in the axial-rhombohedral angle for oxygen-rich NiO. Conversely, no significant distortion was noticed in the NiO system present as a secondary phase within Zn1-xNixO. Nevertheless, the unit-cell volume of both wurtzite h.c.p. Zn1-xNixO and f.c.c. NiO exhibits an anomalous behavior between 150 and 300 degrees C. The origin of such unusual change in the unit-cell volume was discussed in terms of oxygen stoichiometry.

Nickel substitution induced effects on gas sensing properties of cobalt ferrite nanoparticles

Ni2+ ion induced unusual conductivity reversal and an enhancement in the gas sensing properties of ferrites based gas sensors, is reported. The Co1-xNixFe2O4 (for x = 0, 0.5 and 1) nanoparticles were synthesized by wet chemical co-precipitation method and gas sensing properties were studied as a function of composition and temperature. The structural, morphological and microstructural characterization revealed crystallite size of in the range 10-20 nm with porous morphology consisting of nano-sized grains. The Energy Dispersive X-ray (EDX) mapping confirms homogeneous distribution of Co, Ni, Fe and O elements in the ferrites. The non-stoichiometry of the inverse spinel type ferrites and the relative concentration of Ni3+/Co3+ defects were studied using X-ray photoelectron spectroscopy. It is found that the addition of Ni2+ ions into cobalt ferrite shows preferred selectivity towards CO gas at high temperature (325 degrees C) and ethanol gas at low temperature (250 degrees C), unlike undoped cobalt ferrite or undoped nickel ferrite, which show similar response for both these gases. Moreover, an unusual conductivity reversal is observed, except cobalt ferrite due to the difference in reactivity of the gases as well as characteristic non-stoichiometry of ferrites. This behavior is highly gas ambient dependent and hence can be well-exploited for selective detection of gases. (C) 2015 Elsevier B.V. All rights reserved.

Binding of carboxylatopillar5]arene with alkyl and aryl ammonium salts in aqueous medium

The complex formation of alkyl ammonium salts by water-soluble carboxylatopillar5] arene (CP5A) in aqueous medium is reported. p-Xylene diammonium salt and a series of secondary alkyl ammonium salts with various alkyl groups have been prepared and investigated for complex formation. All the ammonium salts exhibit strong host-guest complexation with CP5A under neutral aqueous conditions. H-1 NMR, H-1 DOSY and 2D NOESY NMR experiments have been performed to characterize these inclusion complexes. In this study, the hydrophobic and electrostatic interactions govern the complex formation leading to the formation of pseudorotaxane species. Five pseudo2] rotaxanes and one pseudo3] rotaxane were obtained whose association constant values and stoichiometry were evaluated by an NMR titration method. The results indicate the use of ammonium salts as new complimentary synthons for CP5A in aqueous medium, adding to the repertoire of existing recognition motifs such as paraquat and 1,4-bis(pyridinium) derivatives.

Effect of applied pressure on densification of monolithic ZrCx ceramic by reactive hot pressing

The effect of applied pressure on reactive hot pressing (RHP) of zirconium (Zr):graphite (C) in molar ratios of 1:0.5, 1:0.67, 1:0.8, and 1:1 was studied at 1200 degrees C for 60 min. The relative density achievable increased with increasing pressure and ranged from 99% at 4 MPa for ZrC0.5 to 93% for stoichiometric ZrC at 100 MPa. The diminishing influence of pressure on the final density with increasing stoichiometry is attributed to two causes: the decreasing initial volume fraction of the plastically deforming Zr metal which leads to the earlier formation of a contiguous, stress shielding carbide skeleton and the larger molar volume shrinkage during reaction which leads to pore formation in the final stages. A numerical model of the creep densification of a dynamically evolving microstructure predicts densities that are consistent with observations and confirm that the availability of a soft metal is primarily responsible for the achievement of such elevated densification during RHP. The ability to densify nonstoichiometric compositions like ZrC0.5 at pressures as low as 4 MPa offers an alternate route to fabricating dense nonstoichiometric carbides.

Localized Charge Carrier Transport Properties of Zn1-x Ni (x) O/NiO Two-Phase Composites

We report the localized charge carrier transport of two-phase composite Zn1-x Ni (x) O/NiO (0 a parts per thousand currency sign x a parts per thousand currency sign 1) using the temperature dependence of ac-resistivity rho (ac)(T) across the N,el temperature T (N) (= 523 K) of nickel oxide. Our results provide strong evidence to the variable range hopping of charge carriers between the localized states through a mechanism involving spin-dependent activation energies. The temperature variation of carrier hopping energy epsilon (h)(T) and nearest-neighbor exchange-coupling parameter J (ij)(T) evaluated from the small poleron model exhibits a well-defined anomaly across T (N). For all the composite systems, the average exchange-coupling parameter (J (ij))(AVG) nearly equals to 70 meV which is slightly greater than the 60-meV exciton binding energy of pure zinc oxide. The magnitudes of epsilon (h) (similar to 0.17 eV) and J (ij) (similar to 11 meV) of pure NiO synthesized under oxygen-rich conditions are consistent with the previously reported theoretical estimation based on Green's function analysis. A systematic correlation between the oxygen stoichiometry and, epsilon (h)(T) and J (ij)(T) is discussed.