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Clobetasol propionate ointment (CLP

The poultice formulation is a patch containing a large amount of water. It is known that the water contained in the adhesive polymer layer (ADPL) of poultice affects the cooling sensation and skin permeability of the active pharmaceutical ingredient (API). In this study, we evaluated the relationship between the water content in a ketoprofen poultice formulation and the amount of time the poultice was left out at room temperature after removal from the airtight container, as well as the influence of the decreasing water content on the skin permeability of the API. After removing the poultice from the container for 1 h, the mass of the ADPL decreased by approximately 40%. When the near-infrared (NIR) spectrum of the ADPL of poultice was measured, the peaks reflecting the hydroxyl group were attenuated depending on the time left out at room temperature. It is suggested that the changes in the mass and NIR spectrum of the ADPL are caused by the change in the water content. Moreover, when the permeability of API was evaluated on hairless mouse skin, the cumulative skin permeation amount and flux decreased, while the lag time was prolonged as the time left out increased. These results suggest that the skin permeability of the API is impaired by water evaporation and that maintaining the water in the ADPL in poultice is very important from not only the viewpoint of cooling sensation, tackiness and moisturizing but also the skin permeability of the API.

We demonstrated the difference in the distribution state of pharmaceutical ingredients between tacrolimus (TCR) original ointment and six kinds of generic medicines. Two-dimensional imaging and depth analysis using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy and confocal Raman microscopy were used, in addition to the evaluation of pharmaceutical properties, including spreading properties, rheological properties, and amount of solvent. The solvents, such as propylene carbonate and triacetin, in TCR ointments formed liquid droplets and dispersed in hydrocarbon oils. Waxes, white beeswax and beeswax, formed other domains. Confocal Raman microscopy could detect liquid droplet size without coalescence of that on germanium or glass surfaces. The combination of ATR FT-IR and confocal Raman imaging would be a powerful tool to reveal the size and shape of liquid droplets of pharmaceutical ingredients in semisolid formulations.

To clarify the volume of water required to paste pediatric powders, we herein established a standard for the powder paste state by measuring yield values when water was added to powders. The powders used in the present study were selected from 8 types including original and generic drugs. Tipepidine hibenzate is prescribed in the pediatric field in combination with ambroxol hydrochloride and l-carbocysteine. The volumes of water needed to achieve the paste state of ambroxol hydrochloride between the original and generic drugs were similar. However, the volumes of water needed for l-carbocysteine markedly differed between the original and generic drugs due to differences in their additives. The spreadability of the mixture when water was added to the powders was evaluated using a spread meter. Among the powders tested in the present study, the yield value to achieve a paste state with the addition of water was approximately 1000 dyne/cm2. The optimum volume of water estimated from this yield value using the linear proportional relationship for the amount of powder may be applied to the mixture of each pediatric power for dosage/body weight.

The Potts model describes Ising-model-like interacting spin systems with multivalued spin component, and ground-state search problems of the Potts model can be efficiently mapped onto various integer optimization problems thanks to the rich expression of the multivalued spins. Here, we demonstrate a solver of this model based on hybrid computation using physical and digital architectures, wherein a digital computer updates the interaction matrices in the iterative calculations of the physical Ising-model solvers. This update of interactions corresponds to learning from the Ising solutions, which allows us to save resources when embedding a problem in a physical system. We experimentally solved integer optimization problems (graph coloring and graph clustering) with this hybrid architecture in which the physical solver consisted of coupled degenerate optical parametric oscillators.

We analytically and numerically show that the Hillery-Zubairy’s entanglement criterion is satisfied both below and above the threshold of coupled non-degenerate optical parametric oscillators (NOPOs) with strong nonlinear gain saturation and dissipative linear coupling. We investigated two cases: for large pump mode dissipation, below-threshold entanglement is possible only when the parametric interaction has an enough detuning among the signal, idler, and pump photon modes. On the other hand, for a large dissipative coupling, below-threshold entanglement is possible even when there is no detuning in the parametric interaction. In both cases, a non-Gaussian state entanglement criterion is satisfied even at the threshold. Recent progress in nano-photonic devices might make it possible to experimentally demonstrate this phase transition in a coherent XY machine with quantum correlations.

The low-lying dipole strength in the 90,94Zr nuclei was investigated via (p,p′γ) at 80 MeV and (α,α′γ) at 130 MeV. The experiments, made at RCNP, used the magnetic spectrometer Grand Raiden for the scattered particles and the array CAGRA with HPGe detectors for the γ-decay. For 94Zr these are the first data for both reactions and for 90Zr these are the first data with (p,p′γ) and the first ones at high resolution for (α,α′γ). The comparison of the present results for the two nuclei with existing (γ,γ′) data shows that both nuclear probes produce an excitation pattern different than that of the electromagnetic probes. DWBA calculations were made using form factors deduced from transition densities, based on RPA calculations, characterized by a strong neutron component at the nuclear surface. A combined analysis of the two reactions was performed for the first time to investigate the isoscalar character of the 1− states in 90,94Zr. The (p,p′γ) cross section was calculated using values for the isoscalar electric dipole energy-weighted sum rule (E1 ISEWSR) obtained from the (α,α′γ) data. The isoscalar strength for 90Zr was found to exhaust 20 ± 2.5% of the EWSR in the energy range up to 12 MeV. In case of 94Zr, a strength of 9 ± 1.1% of the EWSR was found in the range up to 8.5 MeV. Although an overall general description was obtained in the studied energy intervals, not all proton cross sections were well reproduced using the isoscalar strength from (α,α′γ). This might suggest mixing of isoscalar and isovector components and that this mixing and the degree of collectivity are not the same for all the 1− states below the particle binding energy.

We show that the nonlinear stochastic dynamics of a measurement-feedback-based coherent Ising machine (MFB-CIM) in the presence of quantum noise can be exploited to sample degenerate ground and low-energy spin configurations of the Ising model. We formulate a general discrete-time Gaussian-state model of the MFB-CIM which faithfully captures the nonlinear dynamics present at and above system threshold. This model overcomes the limitations of both mean-field models, which neglect quantum noise, and continuous-time models, which assume long photon lifetimes. Numerical simulations of our model show that when the MFB-CIM is operated in a quantum-noise-dominated regime with short photon lifetimes (i.e., low cavity finesse), homodyne monitoring of the system can efficiently produce samples of low-energy Ising spin configurations, requiring many fewer roundtrips to sample than suggested by established high-finesse, continuous-time models. We find that sampling performance is robust to, or even improved by, turning off or altogether reversing the sign of the parametric drive, but performance is critically reduced in the absence of optical nonlinearity. For the class of MAX-CUT problems with binary-signed edge weights, the number of roundtrips sufficient to fully sample all spin configurations up to the first-excited Ising energy, including all degeneracies, scales as $1.08^N$. At a problem size of $N = 100$ with a few dozen (median of 20) such desired configurations per instance, we have found median sufficient sampling times of $6\times10^6$ roundtrips; in an experimental implementation of an MFB-CIM with a 10 GHz repetition rate, this corresponds to a wall-clock sampling time of 60 ms., Comment: The first two authors contributed equally to this work. 24 pages, 9 figures

We propose a network of open-dissipative quantum oscillators with optical error correction circuits. In the proposed network, the squeezed/anti-squeezed vacuum states of the constituent optical parametric oscillators below the threshold establish quantum correlations through optical mutual coupling, while collective symmetry breaking is induced above the threshold as a decision-making process. This initial search process is followed by a chaotic solution search step facilitated by the optical error correction feedback. As an optical hardware technology, the proposed coherent Ising machine (CIM) has several unique features, such as programmable all-to-all Ising coupling in the optical domain, directional coupling $(J_{ij} \neq J_{ji})$ induced chaotic behavior, and low power operation at room temperature. We study the performance of the proposed CIMs and investigate how the performance scales with different problem sizes. The quantum theory of the proposed CIMs can be used as a heuristic algorithm and efficiently implemented on existing digital platforms. This particular algorithm is derived from the truncated Wigner stochastic differential equation. We find that the various CIMs discussed are effective at solving many problem types, however the optimal algorithm is different depending on the instance. We also find that the proposed optical implementations have the potential for low energy consumption when implemented optically on a thin film LiNbO3 platform.

We present analytical and numerical simulation results for squeezing, entanglement, and quantum discord in a dissipatively coupled coherent Ising machine (CIM). Both analytical solutions and numerical simulation results, which are obtained with positive-$P$, truncated-Wigner, and truncated-Husimi representations for the density operator, predict the presence of entanglement and quantum discord, below and above the threshold of CIM. The entanglement criteria and quantum discord are evaluated as a function of the dissipative coupling strength relative to the background loss. For coupled two DOPOs, while entanglement disappears as the background loss exceeds the Ising coupling strength, the quantum discord remains finite even with a large linear loss. For one-dimensional lattice of DOPOs, while entanglement disappears for DOPO pair with large distance, quantum discord remains finite.

L0-regularization-based compressed sensing (L0-RBCS) has the potential to outperform L1-regularization-based compressed sensing (L1-RBCS), but the optimization in L0-RBCS is difficult because it is a combinatorial optimization problem. To perform optimization in L0-RBCS, we propose a quantum–classical hybrid system consisting of a quantum machine and a classical digital processor. The coherent Ising machine (CIM) is a suitable quantum machine for this system because this optimization problem can only be solved with a densely connected network. To evaluate the performance of the CIM-classical hybrid system theoretically, a truncated Wigner stochastic differential equation (W-SDE) is introduced as a model for the network of degenerate optical parametric oscillators, and macroscopic equations are derived by applying statistical mechanics to the W-SDE. We show that the system performance in principle approaches the theoretical limit of compressed sensing and this hybrid system may exceed the estimation accuracy of L1-RBCS in actual situations, such as in magnetic resonance imaging data analysis.

The coherent Ising machine (CIM) is a network of optical parametric oscillators (OPOs) that solves for the ground state of Ising problems through OPO bifurcation dynamics. Here, we present experimental results comparing the performance of the CIM to quantum annealers (QAs) on two classes of NP-hard optimization problems: ground state calculation of the Sherrington-Kirkpatrick (SK) model and MAX-CUT. While the two machines perform comparably on sparsely-connected problems such as cubic MAX-CUT, on problems with dense connectivity, the QA shows an exponential performance penalty relative to CIMs. We attribute this to the embedding overhead required to map dense problems onto the sparse hardware architecture of the QA, a problem that can be overcome in photonic architectures such as the CIM.

Combination tablets containing multiple active pharmaceutical ingredients (APIs) are expected to improve patient convenience by decreasing the number of tablets to be taken; thus, numerous formulations containing multiple APIs have recently been developed. To allow for dose adjustments based on patient conditions, many tablets have a bisection line to allow equal division of tablets. However, there have been no investigations regarding content uniformity among divided combination tablets. Therefore, in this study, the content uniformity of combination tablets after division was investigated using near IR and low-frequency (LF) Raman spectroscopy imaging as well as the Japanese Pharmacopoeia (JP) content uniformity tests. As model drugs, five tablets of three combination drugs containing 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) and benserazide hydrochloride (BNS) as APIs for treating Parkinson's disease were bisected; the resultant 10 samples were subjected to the JP content uniformity tests. We found that acceptance values of L-DOPA and BNS were 11.0-21.9% and 13.3-17.5%, respectively, with some non-conformity to the maximum allowed acceptance value (15.0%) as per the current JP. Image analyses by near IR showed that L-DOPA, BNS, lactose, and corn starch were uniformly distributed in each tablet; moreover, LF Raman spectroscopy imaging also supported the result that L-DOPA, BNS, and lactose were evenly distributed. Therefore, drug content in the tablets was uniform; thus, careful manipulation was recommended in the tablet bisection. However, the results of bisection line specifications and hardness tests revealed that the ease of division differed depending on the tablets, which warrants attention.

A coherent Ising machine (CIM) is a network of optical parametric oscillators (OPOs), in which the "strongest" collective mode of oscillation at well above threshold corresponds to an optimum solution of a given Ising problem. When a pump rate or network coupling rate is increased from below to above threshold, however, the eigenvectors with a smallest eigenvalue of Ising coupling matrix [J_ij] appear near threshold and impede the machine to relax to true ground states. Two complementary approaches to attack this problem are described here. One approach is to utilize squeezed/anti-squeezed vacuum noise of OPOs below threshold to produce coherent spreading over numerous local minima via quantum noise correlation, which could enable the machine to access either true ground states or excited states with eigen-energies close enough to that of ground states above threshold. The other approach is to implement real-time error correction feedback loop so that the machine migrates from one local minimum to another during an explorative search for ground states. Finally, a set of qualitative analogies connecting the CIM and traditional computer science techniques are pointed out. In particular, belief propagation and survey propagation used in combinatorial optimization are touched upon., Comment: 32 pages and 7 figures

Background The clobetasol propionate cream formulations (CLBCr) belong to the “strongest” group, and are used widely. In addition, those formulations are often used as a mixture with moisturizer. Recently, we evaluated pharmaceutical properties of the CLBCr using near infrared (NIR) spectroscopy, and characteristic NIR spectra depending on the formulation were observed. In the present study, we attempted to evaluate the more diverse pharmaceutical properties of CLBCr, including the stability of mixture of CLBCr and moisturizer. Method Pharmaceutical properties of CLBCr were evaluated using from rheological characteristics, microscopic observation, dye permeability observations, electrical conductivity method, thermogravimetry-differential thermal analysis (TG-DTA) and near infrared (NIR) spectroscopy. Stability of mixtures of CLBCr and moisturizer were evaluated using from dye method and NIR spectroscopy. Results The hardness of Dermovate® (DRM), Glydil® (GDL), and Myalone® (MYA) was greater than that of CLBCr. High concentrations of white beeswax were considered the reason for the hardness of DRM and GDL. On the other hand, the hardness of MYA may be due to the presence of macrogol 6000. After storage of the cream formulations discharged from the tube at room temperature, mass reduction and attenuation of the peak reflecting water of NIR spectroscopy occurred in a time-dependent manner, except for GDL and MYA. Only GDL was shown to be a w/o-type formulation by dye and electric conductivity measurements, which suggested that this was the reason for the lack of changes in the mass or NIR spectrum of samples after storage. In the NIR spectrum of MYA, the peak reflecting water slightly increased in a time-dependent manner, suggesting the water absorption of macrogol 6000. TG-DTA provided curves indicating the presence of water in each formulation, except for MYA, which was consistent with water quantification previously reported. Finally, when mixing the CLBCr with a moisturizer, in any CLBCr, the stability of the mixture with w/o-type moisturizer varies greatly depending on the each CLBCr. Conclusion Thus, even for cream formulations with the same active pharmaceutical ingredient, pharmaceutical properties and stability of mixture with moisturizer may different significantly.

Summary Gpr52 is an orphan G-protein-coupled receptor of unknown physiological function. We found that Gpr52-deficient (Gpr52−/−) mice exhibit leanness associated with reduced liver weight, decreased hepatic de novo lipogenesis, and enhanced insulin sensitivity. Treatment of the hepatoma cell line HepG2 cells with c11, the synthetic GPR52 agonist, increased fatty acid biosynthesis, and GPR52 knockdown (KD) abolished the lipogenic action of c11. In addition, c11 induced the expressions of lipogenic enzymes (SCD1 and ELOVL6), whereas these inductions were attenuated by GPR52-KD. In contrast, cholesterol biosynthesis was not increased by c11, but its basal level was significantly suppressed by GPR52-KD. High-fat diet (HFD)-induced increase in hepatic expression of Pparg2 and its targets (Scd1 and Elovl6) was absent in Gpr52−/− mice with alleviated hepatosteatosis. Our present study showed that hepatic GPR52 promotes the biosynthesis of fatty acid and cholesterol in a ligand-dependent and a constitutive manner, respectively, and Gpr52 participates in HFD-induced fatty acid synthesis in liver., Graphical abstract, Highlights • Hepatosteatosis is inherently an adaptive response to overnutrition to store energy • On the other hand, it can be a pathological condition causing insulin resistance • High-fat diet increases PPARγ2 expression and lipogenesis in liver via GPR52 • Gpr52 ablation protects mice from developing hepatosteatosis and insulin resistance, Human Metabolism; Molecular Biology

The molecular states of ketoprofen and the interaction between ketoprofen and other pharmaceutical excipients in the matrix layer were examined to determine their effect on the pharmaceutical properties of original and generic ketoprofen dermal patches (generic patches A and B). Molecular states of ketoprofen were evaluated using polarized light microscopy, Raman spectroscopy and powder X-ray diffraction. For the original ketoprofen patch, crystalline components were not observed in the matrix layer. However, crystalline ketoprofen was observed in the two generic ketoprofen patches. Moreover, the ketoprofen exhibited hydrogen bonding with the pharmaceutical excipients or patch materials in the generic products. Skin permeation of ketoprofen from the patches was evaluated using hairless mouse skin. Twelve hours after application, the original patch demonstrated the highest level of cumulative skin permeation of ketoprofen. This was followed by generic patch B while generic patch A showed the lowest level of permeation. Fluxes were calculated from the skin permeation profiles. The original patch was approx. 2.4-times faster compared with generic patch A and approximately 1.9-times faster compared with generic patch B. This investigation suggested that pharmaceutical properties such as skin permeability for these types of products are affected by the precipitation of crystalline ketoprofen in the matrix layer and the interaction of ketoprofen with the pharmaceutical excipients or patch materials.

Optical approaches to AI acceleration have gained intense interest recently due to the potentially breakthrough advantages of photonics: high bandwidth, low power consumption, and efficient data movement. We overview leading photonic AI platforms based on beamsplitter mesh networks, weight banks, and photoelectric multiplication. While the theoretical performance can be orders of magnitude beyond current state of the art, practical issues of chip area, input / output, and crosstalk paint a more nuanced near-term picture of photonic AI acceleration. Both fundamental and near-term limitations to energy efficiency are addressed, and bandwidth limitations due to temporal crosstalk are analyzed.

The purpose of this study is to verify the usefulness of near infrared (NIR) spectroscopy for evaluation of pharmaceutical properties of cream formulations. The present study examined in detail the pharmaceutical properties of clobetasol propionate (CLB) cream formulations using NIR spectroscopy. The characteristic NIR spectrum of Dermovate ® (DRM), the original CLB cream formulation displayed a shoulder around 4800 cm −1 as well as absorption around 5200 cm −1 . A high concentration of propylene glycol (PG) in DRM was thought to be the main contributing factor to this characteristic aspect of the spectrum. Only a peak with absorption around 5200 cm −1 was obtained from the generic CLB creams, except for Myalone ® (MYA), suggesting a lower concentration of PG in those generic formulations compared to the original formulation. The spectrum obtained from the analysis of MYA was significantly different from the other formulations. The fact that it contained macrogol and a high PG concentration were likely the major factors that accounted for the spectral differences. High concentrations (25–30%) of PG were found in DRM and MYA by gas chromatography–mass spectrometry. Thus, even cream formulations with the same active pharmaceutical ingredients can have significantly different pharmaceutical properties. And it is suggested usefulness of NIR spectroscopy for evaluation of pharmaceutical property of cream formulation.