Screening a trace amount of pharmaceutical cocrystals by using an enhanced nano-spot method.

Cocrystallization is an attractive and promising technology that can improve the physical properties of formulations of active pharmaceutical ingredients (APIs). We have developed a "nano-spot method" that can evaluate the crystalline form on the nanogram scale. In this study, the following studies were performed to obtain versatile and comprehensive improvements to the nano-spot method: modification of the sample solution, application of solvent vapor exposure to attempt the precipitation of various states of crystals, and adoption of low-frequency Raman spectroscopy.

In situ monitoring of cocrystals in formulation development using low-frequency Raman spectroscopy.

In recent years, to guarantee a quality-by-design approach to the development of pharmaceutical products, it is important to identify properties of raw materials and excipients in order to determine critical process parameters and critical quality attributes. Feedback obtained from real-time analyses using various process analytical technology (PAT) tools has been actively investigated. In this study, in situ monitoring using low-frequency (LF) Raman spectroscopy (10-200 cm), which may have higher discriminative ability among polymorphs than near-infrared spectroscopy and conventional Raman spectroscopy (200-1800 cm), was investigated as a possible application to PAT.

Ground states of the SU(N) Heisenberg model.

The SU(N) Heisenberg model with various single-row representations is investigated by quantum Monte Carlo simulations. While the zero-temperature phase boundary agrees qualitatively with the theoretical predictions based on the 1/N expansion, some unexpected features are also observed. For N> or =5 with the fundamental representation, for example, it is suggested that the ground states possess exact or approximate U(1) degeneracy.