Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

MRI as a promising tool for evaluation of the stability of cosmetic emulsions.

OBJECTIVE: We have recently established a novel method to evaluate the emulsion stability of pharmaceutical skin cream. The key technology of the method is magnetic resonance imaging (MRI). The purpose of this study was to verify the usefulness of the method in the cosmetic industry. METHODS: Milky lotion-type emulsions were employed as test samples. We note that the test samples were prepared by taking account of commercial milky lotions. After the sample preparation, a centrifugation treatment (5000 g for up to 120 min) was implemented to accelerate their destabilization processes. The centrifuged samples were monitored by using T2 relaxation time (T2 ) maps. Furthermore, the histograms generated from the T2 maps were analysed to investigate the destabilization process in more detail. In addition, small fractions of the upper and lower phases were collected from the centrifuged samples, and microscopic observations were conducted. RESULTS: T2 maps successfully visualized the destabilization process accompanying the centrifugation protocol. From the microscopic observations, it was clarified that the main mechanism of the destabilization process was creaming. The sensitivity of the T2 map to creaming was much superior to that of visible observation; the T2 map can detect a slight creaming that is not visible to the naked eye. In addition, the T2 map also enables the detection of slight reversible creaming-dispersion changes accompanied by a repeated centrifugation-vortexing treatment. By using the parameters derived from the histogram analysis, the creaming behaviour can be evaluated more precisely and more objectively. This study prepared emulsions containing different thickener contents and then compared their creaming behaviours. As a consequence of the analysis, we could fully evaluate the effect of thickener on the emulsion stability by the evaluation method. CONCLUSION: MRI is a promising tool for evaluation of the stability of cosmetic emulsions.

Role of valence fluctuations in the superconductivity of Ce122 compounds.

Pressure dependence of the Ce valence in CeCu(2)Ge(2) has been measured up to 24 GPa at 300 K and to 17 GPa at 18-20 K using x-ray absorption spectroscopy in the partial fluorescence yield. A smooth increase of the Ce valence with pressure is observed across the two superconducting (SC) regions without any noticeable irregularity. The chemical pressure dependence of the Ce valence was also measured in Ce(Cu(1-x)Ni(x))(2)Si(2) at 20 K. A very weak, monotonic increase of the valence with x was observed, without any significant change in the two SC regions. Within experimental uncertainties, our results show no evidence for the valence transition with an abrupt change in the valence state near the SC II region, challenging the valence-fluctuation mediated superconductivity model in these compounds at high pressure and low temperature.

Direct observation of lattice symmetry breaking at the hidden-order transition in URu2Si2.

Since the 1985 discovery of the phase transition at THO=17.5 K in the heavy-fermion metal URu2Si2, neither symmetry change in the crystal structure nor large magnetic moment that can account for the entropy change has been observed, which makes this hidden order enigmatic. Recent high-field experiments have suggested electronic nematicity that breaks fourfold rotational symmetry, but direct evidence has been lacking for its ground state in the absence of magnetic field. Here we report on the observation of lattice symmetry breaking from the fourfold tetragonal to twofold orthorhombic structure by high-resolution synchrotron X-ray diffraction measurements at zero field, which pins down the space symmetry of the order. Small orthorhombic symmetry-breaking distortion sets in at THO with a jump, uncovering the weakly first-order nature of the hidden-order transition. This distortion is observed only in ultrapure samples, implying a highly unusual coupling nature between the electronic nematicity and underlying lattice.

Possibility of valence-fluctuatsion-mediated superconductivity in Cd-doped CeIrIn(5) probed by In NQR.

We report on a pressure-induced evolution of exotic superconductivity and spin correlations in CeIr(In(1-x)Cd(x))(5) by means of in-nuclear-quadrupole-resonance (NQR) studies. Measurements of an NQR spectrum and nuclear-spin-lattice-relaxation rate 1/T(1) have revealed that antiferromagnetism induced by Cd doping emerges locally around Cd dopants, but superconductivity is suddenly induced at T(c)=0.7 and 0.9 K at 2.34 and 2.75 GPa, respectively. The unique superconducting characteristics with a large fraction of the residual density of state at the Fermi level which increases with T(c) differ from those for anisotropic superconductivity mediated by antiferromagnetic correlations. By incorporating the pressure dependence of the NQR frequency pointing to the valence change of Ce, we suggest that unconventional superconductivity in the CeIr(In(1-x)Cd(x))(5) system may be mediated by valence fluctuations.

Cyclotron resonance in the hidden-order phase of URu2Si2.

We report the first observation of cyclotron resonance in the hidden-order phase of ultraclean URu2Si2 crystals, which allows the full determination of angle-dependent electron-mass structure of the main Fermi-surface sheets. We find an anomalous splitting of the sharpest resonance line under in-plane magnetic-field rotation. This is most naturally explained by the domain formation, which breaks the fourfold rotational symmetry of the underlying tetragonal lattice. The results reveal the emergence of an in-plane mass anisotropy with hot spots along the [110] direction, which can account for the anisotropic in-plane magnetic susceptibility reported recently. This is consistent with the "nematic" Fermi liquid state, in which itinerant electrons have unidirectional correlations.

Twofold spontaneous symmetry breaking in the heavy-fermion superconductor UPt3.

The field-orientation dependent thermal conductivity of the heavy-fermion superconductor UPt3 was measured down to very low temperatures and under magnetic fields throughout the distinct superconducting phases: B and C phases. In the C phase, a striking twofold oscillation of the thermal conductivity within the basal plane is resolved reflecting the superconducting gap structure with a line of node along the a axis. Moreover, we find an abrupt vanishing of the oscillation across a transition to the B phase, as a clear indication of a change of gap symmetries. We also identify extra two line nodes below and above the equator in both B and C phases. From these results together with the symmetry consideration, the gap function of UPt3 is determined as a E(1u) representation characterized by a combination of two line nodes at the tropics and point nodes at the poles.

Rotational symmetry breaking in the hidden-order phase of URu2Si2.

A second-order phase transition is characterized by spontaneous symmetry breaking. The nature of the broken symmetry in the so-called "hidden-order" phase transition in the heavy-fermion compound URu(2)Si(2), at transition temperature T(h) = 17.5 K, has posed a long-standing mystery. We report the emergence of an in-plane anisotropy of the magnetic susceptibility below T(h), which breaks the four-fold rotational symmetry of the tetragonal URu(2)Si(2). Two-fold oscillations in the magnetic torque under in-plane field rotation were sensitively detected in small pure crystals. Our findings suggest that the hidden-order phase is an electronic "nematic" phase, a translationally invariant metallic phase with spontaneous breaking of rotational symmetry.

Spin susceptibility of noncentrosymmetric heavy-fermion superconductor CeIrSi3 under pressure: 29Si Knight-shift study on single crystal.

We report 29Si NMR study on a single crystal of the heavy-fermion superconductor CeIrSi3 without an inversion symmetry along the c axis. The 29Si Knight-shift measurements under pressure have revealed that the spin susceptibility for the ab plane decreases slightly below T(c), whereas along the c axis it does not change at all. The result can be accounted for by the spin susceptibility in the superconducting state being dominated by the strong antisymmetric (Rashba-type) spin-orbit interaction that originates from the absence of an inversion center along the c axis and it being much larger than superconducting condensation energy. This is the first observation which exhibits an anisotropy of the spin susceptibility below T(c) in the noncentrosymmetric superconductor dominated by strong Rashba-type spin-orbit interaction.

Sign reversal of field-angle resolved heat capacity oscillations in a heavy Fermion superconductor CeCoIn5 and d{x{2}-y{2}} pairing symmetry.

To identify the superconducting gap symmetry in CeCoIn5 (T{c}=2.3 K), we measured the angle-resolved specific heat (C{phi}) in a field rotated around the c axis down to a very low temperature, 0.05T{c}, and made detailed theoretical calculations. In a field of 1 T, a sign reversal of the fourfold angular oscillation in C{phi} was observed at T approximately 0.1T{c} upon entering a quasiclassical regime where the maximum of C{phi} corresponds to the antinodal direction, coinciding with the angle-resolved density of states (ADOS) calculation. The C{phi} behavior, which exhibits minima along the [110] directions, unambiguously allows us to conclude d{x{2}-y{2}} symmetry of this system. The ADOS-quasiclassical region is confined to a narrow T and H domain within T/T{c} approximately 0.1 and 1.5 T (0.13H{c2}).

Evolution of the Fermi surface of BaFe2(As1-xPx){2} on entering the superconducting dome.

Using the de Haas-van Alphen effect we have measured the evolution of the Fermi surface of BaFe2(As1-xPx){2} as a function of isoelectric substitution (As/P) for 0.41

Prediction of permeability of FD-4 through porous poly (2-hydroxyethyl methacrylate) membrane by multiple linear regression and artificial neural network.

The aim of this study was to predict the permeability through porous poly (2-hydroxyethyl methacrylate) (pHEMA) membranes of fluorescein isothiocyanate-labeled dextran molecular weight 4400 (FD-4) as a model of peptide and protein drug movement. Homogeneous standard membranes were prepared by redox polymerization. Permeability data were predicted by an artificial neural network (ANN) as a function of polymerization factors, and the accuracy was compared with that of conventional multiple linear regression (MLR). Good linearity was observed with each model, with the correlation coefficient of a leave-one-out cross-validation (Rcross) being 0.857 for the MLR model and 0.876 for the ANN model. The mean bias and mean accuracy for the ANN were somewhat smaller than those of the MLR. The ANN method provides an accurate quantitative approximation of the permeability coefficient of FD-4, as judged by conventional MLR, and could be applied to prediction of the non-linear relation between polymerization factors and the permeability of FD-4.

Possible phase transition deep inside the hidden order phase of ultraclean URu2Si2.

To elucidate the underlying nature of the hidden order (HO) state in heavy-fermion compound URu(2)Si(2), we measure electrical transport properties of ultraclean crystals in a high field, low temperature regime. Unlike previous studies, the present system with much less impurity scattering resolves a distinct anomaly of the Hall resistivity at H;{*} = 22.5 T, well below the destruction field of the HO phase = or approximately 36 T. In addition, a novel quantum oscillation appears above a magnetic field slightly below H;{*}. These results indicate an abrupt reconstruction of the Fermi surface, which implies a possible phase transition well within the HO phase caused by a band-dependent destruction of the HO parameter.

Point-contact spectroscopy of the heavy-fermion superconductor CePt(3)Si.

Differential resistance spectra (dV/dI-V characteristics) have been measured for point contacts between the heavy-fermion superconductor (HFS) CePt(3)Si and a normal metal. Some contacts show a peak at V = 0 that is characteristic of HFS coexisting with a magnetic order such as UPd(2)Al(3), UNi(2)Al(3) and URu(2)Si(2). The evolution of the peak occurs well above the antiferromagnetic transition temperature T(N)∼2.2 K, so that the direct relationship with the magnetic transition is questionable. The half-width of the peak seems to reflect the crystal field splitting or the spin-wave gap as observed for the above-mentioned HFSs, possibly suggesting that some common scattering process induces the zero-bias peaks in these materials.

Unconventional superconductivity of NpPd(5)Al(2).

The high quality single crystals of NpPd(5)Al(2) with the body-centered tetragonal structure were grown by the Pb flux method. NpPd(5)Al(2) was found to be the first Np-based heavy fermion superconductor with the relatively high critical temperature T(sc) = 4.9 K. The upper critical field H(c2) is large and highly anisotropic. Corresponding to the heavy electronic state, the initial slope of H(c2) is large, but H(c2) at low temperatures is suppressed by the magnetic field, indicating a strong Pauli paramagnetic effect and the first-order transition at H(c2). These results imply that NpPd(5)Al(2) is located at the proximity of the antiferromagnetic ordering, which might be hidden by the superconductivity. The d-wave superconductivity with a spin singlet state is most likely realized in NpPd(5)Al(2).

Novel quantum criticality in CeRu2Si2 near absolute zero observed by thermal expansion and magnetostriction.

We report linear thermal expansion and magnetostriction measurements for CeRu2Si2 in magnetic fields up to 52.6 mT and at temperatures down to 1 mK. At high temperatures, this compound showed Landau-Fermi-liquid behavior: The linear thermal expansion coefficient and the magnetostriction coefficient were proportional to the temperature and magnetic field, respectively. In contrast, a pronounced non-Fermi-liquid effect was found below 50 mK. The negative contribution of thermal expansion and magnetostriction suggests the existence of an additional quantum critical point.

Enhancement of superconducting transition temperature due to the strong antiferromagnetic spin fluctuations in the noncentrosymmetric heavy-fermion superconductor CeIrSi3: A 29Si NMR study under pressure.

We report a (29)Si NMR study on the pressure-induced superconductivity (SC) in an antiferromagnetic (AFM) heavy-fermion compound CeIrSi(3) without inversion symmetry. In the SC state at P = 2.7-2.8 GPa, the temperature (T) dependence of the nuclear-spin lattice relaxation rate 1/T(1) below T(c) exhibits a T(3) behavior without any coherence peak just below T(c), revealing the presence of line nodes in the SC gap. In the normal state, 1/T(1) follows a square root T-like behavior, suggesting that the SC emerges under the non-Fermi-liquid state dominated by AFM spin fluctuations enhanced around a quantum critical point. The reason why the maximum T(c) in CeIrSi(3) is relatively high among the Ce-based heavy-fermion superconductors may be the existence of the strong AFM spin fluctuations. We discuss the comparison with the other Ce-based heavy-fermion superconductors.

Flux line lattice melting and the formation of a coherent quasiparticle Bloch state in the ultraclean URu2Si2 superconductor.

We find that in the ultraclean heavy-fermion superconductor URu(2)Si(2) (T_{c0}=1.45 K) a distinct flux line lattice melting transition with outstanding characters occurs well below the mean-field upper critical fields. We show that a very small number of carriers with heavy mass in this system results in exceptionally large thermal fluctuations even at sub-Kelvin temperatures, which are witnessed by a sizable region of the flux line liquid phase. The uniqueness is further highlighted by an enhancement of the quasiparticle mean free path below the melting transition, implying a possible formation of a quasiparticle Bloch state in the periodic flux line lattice.

Factors affecting release rate of diltiazem hydrochloride from poly (2-hydroxyethyl methacrylate) matrices.

Sustained release diltiazem hydrochloride (DIL) formulation is widely used over 110 countries worldwide, and is among the drugs recommended as a first-line therapy in the major guidelines for the management of hypertension. In search for a most suitable controlled release formulation of DIL, we investigated poly (2-hydroxyethyl methacrylate) matrix (pHEMA matrix) synthesized by photopolymerization. Factors affecting the release rate of DIL from pHEMA matrices were investigated, focusing on the internal structure of the matrices. The effects of the porosity (epsilon), the fractal dimensions (Df) and the microscopic viscosity (eta matrix) of the matrices on the release rate of DIL were investigated on the basis of the linear least square equation as well as the Higuchi's equation. A relation between the actual value and predicted value based on the linear least square equation exhibited a fairly good linearity (r=0.979). Furthermore, the release rate of DIL was represented based on the Higuchi's equation including the values of epsilon, Df and eta matrix. It is likely that the release rate of DIL from pHEMA matrices is mainly controlled by epsilon and Df, but eta matrix was less effective.

Exotic superconducting properties in the electron-hole-compensated heavy-fermion "Semimetal" URu2Si2.

We show that the charge and thermal transport measurements on ultraclean crystals of URu2Si2 reveal a number of unprecedented superconducting properties. The uniqueness is best highlighted by the peculiar field dependence of thermal conductivity including the first-order transition at Hc2 with a reduction of entropy flow. This is a consequence of multiband superconductivity with compensated electronic structure in the hidden order state of this system. We provide strong evidence for a new type of unconventional superconductivity with two distinct gaps having different nodal topology.