A new benzofuroquinoline derivative, 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one (KCA-098), shows poor oral absorption due to practical insolubility in water. In this study, a co-grinding technique employing a water-soluble polymer was used for improvement of the dissolution rate of KCA-098. Powder X-ray diffraction patterns and IR spectra of KCA-098 showed the conversion of the drug from a crystal state to an amorphous state by grinding with a polymer such as hydroxypropyl cellulose (HPC-SL) or polyvinylpyrrolidone (PVP K30). The particle size of KCA-098 was remarkably reduced to a submicron size by grinding with HPC-SL. The co-ground mixture with HPC-SL showed a rapid dissolution rate and maintained supersaturation for more than 1 h. On the other hand, the co-ground mixture with PVP K30 showed rapid dissolution and supersaturation for a shorter period. These data suggest that the rapid dissolution rate was obtained by the conversion of the drug particles from a crystal to amorphous state by grinding with water-soluble polymers and that a reduction in particle size to the submicron level led to the maintenance of supersaturation due to good dispersion.

Transitions in the qualitative behavior of chemical reaction dynamics with a decrease in molecule number have attracted much attention. Here, a method based on a Markov process with a tridiagonal transition matrix is applied to the analysis of this transition in reaction dynamics. The transition to bistability due to the small-number effect and the mean switching time between the bistable states are analytically calculated in agreement with numerical simulations. In addition, a novel transition involving the reversal of the chemical reaction flow is found in the model under an external flow, and also in a three-component model. The generality of this transition and its correspondence to biological phenomena are also discussed.

The excitation and emission spectra of CaWO4, MgWO4, PbWO4, ZnWO4, and CaMoO4 were analyzed by a configurational coordination model. The spectral line shapes simulated by a configurational coordination model with a singlet ground state and an excited triplet state well explained the line shape of the luminescence spectra and the line shape at the rising part of the excitation spectra of these salts at room temperature. The energy level of the excited triplet state and the reorganization energies at the ground sate and the triplet state were determined. It was concluded that the potential curve at the excited state becomes shallower than that at the ground state for these systems.

A method based on multicanonical Monte Carlo is applied to the calculation of large deviations in the largest eigenvalue of random matrices. The method is successfully tested with the Gaussian orthogonal ensemble, sparse random matrices, and matrices whose components are subject to uniform density. Specifically, the probability that all eigenvalues of a matrix are negative is estimated in these cases down to the values of ∼10(-200), a region where simple random sampling is ineffective. The method can be applied to any ensemble of matrices and used for sampling rare events characterized by any statistics.

Multicanonical MCMC (Multicanonical Markov Chain Monte Carlo; Multicanonical Monte Carlo) is discussed as a method of rare event sampling. Starting from a review of the generic framework of importance sampling, multicanonical MCMC is introduced, followed by applications in random matrices, random graphs, and chaotic dynamical systems. Replica exchange MCMC (also known as parallel tempering or Metropolis-coupled MCMC) is also explained as an alternative to multicanonical MCMC. In the last section, multicanonical MCMC is applied to data surrogation; a successful implementation in surrogating time series is shown. In the appendices, calculation of averages and normalizing constant in an exponential family, phase coexistence, simulated tempering, parallelization, and multivariate extensions are discussed.