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.

Investigations on growth, structure, optical properties and laser damage threshold of organic nonlinear optical crystals of Guanidinium L-Ascorbate

Single crystals of Guanidinium L-Ascorbate (GuLA) were grown and crystal structure was determined by direct methods. GuLA crystallizes in orthorhombic, non-centrosymmetric space group P2(1)2(1)2(1). The UV-cutoff was determined as 325 nm. The morphology was generated and the interplanar angles estimated and compared with experimental values. Second harmonic generation conversion efficiency was measured and compared with other salts of L-Ascorbic acid. Surface laser damage threshold was calculated as 11.3GW/cm(2) for a single shot of laser of 1064 nm wavelength.

Anisotropy in the mechanical properties of organic crystals: temperature dependence

The nanoindentation technique has recently been utilized for quantitative evaluation of the mechanical properties of molecular materials successfully, including their temperature (T) dependence. In this paper, we examine how the mechanical anisotropy varies with T in saccharin and L-alanine single crystals. Our results show that elastic modulus (E) decreases linearly in all the cases examined, with the T-dependence of E being anisotropic. Correspondence between directional dependence of the slopes of the E vs. T plots and the linear thermal expansion coefficients was found. The T-dependence of hardness (H), on the other hand, was found to be nonlinear and significant when (100) of saccharin and (001) of L-alanine are indented. While the anisotropies in E and H of saccharin and E of L-alanine enhance with T, the anisotropy in H of L-alanine was found to reduce with T. Possible mechanistic origins of these variations are discussed.

Structure-mechanical property correlations in mechanochromic luminescent crystals of boron difluoride dibenzoylmethane derivatives

The structure and mechanical properties of crystalline materials of three boron difluoride dibenzoylmethane (BF(2)dbm) derivatives were investigated to examine the correlation, if any, among mechanochromic luminescence (ML) behaviour, solid-state structure, and the mechanical behaviour of single crystals. Qualitative mechanical deformation tests show that the crystals of BF(2)dbm(Bu-t)(2) can be bent permanently, whereas those of BF(2)dbm(OMe)(2) exhibit an inhomogeneous shearing mode of deformation, and finally BF(2)dbmOMe crystals are brittle. Quantitative mechanical analysis by nanoindentation on the major facets of the crystals shows that BF(2)dbm(Bu-t)(2) is soft and compliant with low values of elastic modulus, E, and hardness, H, confirming its superior suceptibility for plastic deformation, which is attributed to the presence of a multitude of slip systems in the crystal structure. In contrast, both BF(2)dbm(OMe)(2) and BF(2)dbmOMe are considerably stiffer and harder with comparable E and H, which are rationalized through analysis of the structural attributes such as the intermolecular interactions, slip systems and their relative orientation with respect to the indentation direction. As expected from the qualitative mechanical behaviour, prominent ML was observed in BF(2)dbm(Bu-t)(2), whereas BF(2)dbm(OMe)(2) exhibits only a moderate ML and BF(2)dbmOMe shows no detectable ML, all examined under identical conditions. These results confirm that the extent of ML in crystalline organic solid-state fluorophore materials can be correlated positively with the extent of plasticity (low recovery). In turn, they offer opportunities to design new and improved efficient ML materials using crystal engineering principles.

An anisotropic elastic-plastic constitutive model for single and polycrystalline metals .1. Theoretical developments

An anisotropic elastic-plastic constitutive model for single and polycrystalline metals is proposed. The anisotropic hardening of single crystals, at first, is discussed with the viewpoint of yield surface and a new formulation of it is proposed. Then, a model for the anisotropic hardening of polycrystals is suggested by increasing the number of slip systems and incorporating the interaction of all slip systems. The interaction of grains through grain boundaries is shown to be similar to, and incorporated into, the interaction of slip systems in grains. The numerical predictions and their comparisons with experiments will follow in Part II of this paper.

Preliminary-results of gaas single-crystal growth under high gravity conditions

GaAs single crystals have been grown under high gravity conditions, up to 9g0, by a recrystallization method with decreasing temperature. The impurity striations in GaAs grown under high gravity become weak and indistinct with smaller striation spacings. The dislocation density of surcharge-grown GaAs increases with increase of centrifugal force. The cathodoluminescence results also show worse perfection in the GaAs grown at high gravity than at normal earth gravity.

3D Finite Volume Scheme for Czochralski Single Crystal Growth

Czochralski (Cz) technique, which is used for growing single crystals, has dominated the production of single crystals for electronic applications. The Cz growth process involves multiple phases, moving interface and three-dimensional behavior. Much has been done to study these phenomena by means of numerical methods as well as experimental observations. A three-dimensional curvilinear finite volume based algorithm has been developed to model the Cz process. A body-fitted transformation based approach is adopted in conjunction with a multizone adaptive grid generation (MAGG) technique to accurately handle the three-dimensional problems of phase-change in irregular geometries with free and moving surfaces. The multizone adaptive model is used to perform a three-dimensional simulation of the Cz growth of silicon single crystals.Since the phase change interface are irregular in shape and they move in response to the solution, accurate treatment of these interfaces is important from numerical accuracy point of view. The multizone adaptive grid generation (MAGG) is the appropriate scheme for this purpose. Another challenge encountered is the moving and periodic boundary conditions, which is essential to the numerical solution of the governing equations. Special treatments are implemented to impose the periodic boundary condition in a particular direction and to determine the internal boundary position and shape varying with the combination of ambient physicochemical transport process and interfacial dynamics. As indicated above that the applications and processes characterized by multi-phase, moving interfaces and irregular shape render the associated physical phenomena three-dimensional and unsteady. Therefore a generalized 3D model rather than a 2D simulation, in which the governing equations are solved in a general non-orthogonal coordinate system, is constructed to describe and capture the features of the growth process. All this has been implemented and validated by using it to model the low pressure Cz growth of silicon. Accuracy of this scheme is demonstrated by agreement of simulation data with available experimental data. Using the quasi-steady state approximation, it is shown that the flow and temperature fields in the melt under certain operating conditions become asymmetric and unsteady even in the absence of extrinsic sources of asymmetry. Asymmetry in the flow and temperature fields, caused by high shear initiated phenomena, affects the interface shape in the azimuthal direction thus results in the thermal stress distribution in the vicinity, which has serious implications from crystal quality point of view.

Gamma-ray induced color centers in Yb : YAG crystals grown by Czochralski method

20 at.% Yb:YAG single crystals have been grown by the CZ method and gamma-ray irradiation induced color centers and valence change of Fe3+ and Yb3+ ions in Yb:YAG have been studied. One significant 255 nm absorption band was observed in as-grown crystals and was attributed to Fe3+ ions. Two additional absorption (AA) bands located at 255 nm and 345 nm, respectively, were produced after gamma irradiation. The changes in the AA spectra after gamma irradiation and air annealing are mainly related to the charge exchange of the Fe3+, Fe2+, oxygen vacancies and F-type color centers. Analysis shows that the broad AA band is associated with Fe2+ ions and F-type color centers. The transition Yb3+ Yb2+ takes place as an effect of recharging of one of the Yb3+ ions from a pair in the process of gamma irradiation. (C) 2006 Elsevier Ltd. All rights reserved.

Crystal growth and spectroscopic characterization of Yb-doped and Yb, Na-codoped CaF2 laser crystals by TGT

High-quality 2at%-doped Yb:CaF2 and Yb,Na:CaF2 single crystals with diameter of 76mm were grown by the temperature gradient technique. For the first time, distribution coefficients (KO) of Yb in the two crystals were determined to be 1.07 and 0.91, respectively, by measuring the Yb concentrations at the growth starting position in the as-grown boules. Absorption and emission spectra of the two different crystals were measured at room temperature. Experimental results show that Na+ ions codoping with Yb3+ as charge compensators make Yb3+ ions in CaF2 lattice to be a quasi-single-center system, and greatly suppress the deoxidization of Yb3+ to Yb2+ (c) 2005 Elsevier B.V. All rights reserved.

Blue upconversion luminescence generation in Ce3+: Gd2SiO5 crystals by infrared femtosecond laser irradiation

Blue frequency-upconversion fluorescence emission has been observed in Ce3+-doped Gd2SiO5 single crystals, pumped with 120-fs 800 nm IR laser pulses. The observed fluorescence emission peaks at about 440nm is due to 5d -> 4f transition of Ce3+ ions. The intensity dependence of the blue fluorescence emission on the IR excitation laser power obeys the cubic law, demonstrating three-photon absorption process. Analysis suggested that three-photon simultaneous absorption induced population inversion should be the predominant frequency upconversion mechanism. (c) 2006 Optical Society of America.

Color centers in Yb : YAG crystals grown by temperature-gradient techniques

Yb: YAG (Yb: Y3Al5O12) crystals have been grown by temperature-gradient techniques (TGT) and their color centers and impurity defects were investigated by means of gamma irradiations and thermal treatment. Two color centers located at 255 and 290 nm were observed in the as-grown TGT-Yb: YAG. Analysis shows that the 255 nm band may be associated with Fe3+ ions. Absorption intensity changes of the 290 nm band after gamma irradiation and thermal treatment indicate that this band may be associated with oxygen-vacancy defects. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectra analysis of a novel Ti-doped LiAlO2 single crystal

LiAlO2 single crystals doped with Ti at concentration 0.2 at.% are grown by the Czochralskl technique with dimensions Phi 42 x 55 mm. Ti ions in the crystal are quadrivalence proven by comparing the absorption and fluorescence spectra of pure LiAlO2 and Ti: LiAlO2. After air and Li-rich atmosphere annealing, the absorption peaks in the range of 600-800nm disappear. We conclude that 682 and 756nm absorption peaks are attributed to the V-Li and V-O absorptions, respectively. The peaks at 716nm and 798nm may stem from the V-Li(+) and F+ absorptions. The colour-centre model can be applied to explain the experimental phenomena. Ti4+-doping produces more lithium vacancies in the LiAlO2 crystal. The intensities of [LiO4] and the associated bonds remain unchanged, which improves the anti-hydrolyzation and thermal stability of LiAlO2 crystals.

Single crystal beta-Ga2O3: Cr grown by floating zone technique and its optical properties

beta-Ga2O3: Cr single crystals were grown by floating zone technique. Absorption spectra and fluorescence spectra were measured at room temperature. The values of field splitting parameter Dq and Racah parameter B were obtained by the peak values of absorption spectra. The value 10Dq/B=23.14 manifests that in beta-Ga2O3 crystals Cr3+ ions are influenced by low energy crystal field. After high temperature annealing in air, the Cr3+ intrinsic emission was enhanced and the green luminescence disappeared. The strong and broad 691 nm emission was obtained at 420 nm excitation due to the electron transition occurred from T-4(2) to (4)A(2). The studies manifest that the beta-Ga2O3 crystals have the potential application for tunable laser.

Growth of ZnO single crystal by chemical vapor transport method

ZnO crystals were grown by CVT method in closed quartz tube under seeded condition. Carbon was used as a transport agent to enhance the chemical transport of ZnO in the growth process. ZnO single crystals were grown by using GaN/sapphire and GaN/Si wafer as seeds. The property and crystal quality of the ZnO single crystals was studied by photoluminescence spectroscopy and X-ray diffraction technique.

Growth of ZnO single crystal by chemical vapor transport method

ZnO crystals were grown by CVT method in closed quartz tube under seeded condition. Carbon was used as a transport agent to enhance the chemical transport of ZnO in the growth process. ZnO single crystals were grown by using GaN/sapphire and GaN/Si wafer as seeds. The property and crystal quality of the ZnO single crystals was studied by photoluminescence spectroscopy and X-ray diffraction technique.