In this study, the time-dependent evolution of amorphous probucol nanoparticles was characterized by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). The nanoparticles were formed by dispersing ternary solid dispersions of probucol in water. Spray drying and cogrinding were used to prepare a spray-dried sample (SPD) and two ground-mixture samples (GM­(I) and GM­(II)) of probucol (PBC) form I and form II/hypromellose/sodium dodecyl sulfate ternary solid dispersions. The amorphization of PBC in the SPDs and GMs was confirmed using powder X-ray diffraction (PXRD) and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Additionally, differential scanning calorimetry showed that relatively small amounts of PBC nuclei or PBC-rich domains remained in both GMs. Then, the physical stability of drug nanoparticles formed after aqueous dispersion in the SPD and GM suspensions during storage at 40 °C was characterized. Cryogenic transmission electron microscopy was used to monitor the evolution of the amorphous PBC nanoparticles in the SPD and GM suspensions during storage. Spherical nanoparticles smaller than 30 nm were observed in all of the suspensions just after dispersion. The size of the particles in the SPD suspension gradually increased but remained on the order of nanometers and retained their spherical shape during storage. In contrast, both GM suspensions evolved through three morphologies, spherical nanoparticles that gradually increased in size, needle-like nanocrystals, and micrometer-sized crystals with various shapes. The evolution of the nanoparticles suggested that their stability in the GM suspension was lower than in the SPD suspension. PXRD analysis of the freeze-dried suspensions of the particles showed that the PBC in the nanoparticles of the SPD suspension was in the amorphous state just after dispersion, while a small fraction of the PBC in the nanoparticles of the GM suspension exhibited a crystal phase and selectively crystallized to its initial crystal form during storage. AFM force–distance curves also demonstrated the existence of crystal phase PBC in the spherical nanoparticles in the GM suspension just after dispersion. The molecular state of PBC in the ternary solid dispersion was dependent on the preparation method (either completely amorphized or incompletely amorphized with residual nuclei or drug-rich domains) and determined the potential mechanisms of PBC nanoparticle evolution after aqueous dispersion. These findings confirm the importance of the molecular state on the particle evolution and the physical stability of the drug nanoparticles in the suspension. Cryo-TEM and AFM measurements provide more direct insight for designing solid dispersion formulations to produce stable amorphous drug nanosuspensions that efficiently improve the solubility and bioavailability of poorly water-soluble drugs.

High-rate and smooth surface etching of Al2O3-TiC, which is widely used as a slider material for magnetic recording heads, has been developed employing inductively coupled plasma (ICP). The etching rate of 200 nm/min was obtained with Cl2/BCl3 mixture. However the etched morphology exhibited roughness around 40 nm Ra (arithmetic average deviation from center line) because of different etching rates for Al2O3 and TiC grains in the substrate. The addition of Ar to the Cl2/BCl3 improved both the etching rate and roughness of the etched surface considerably. As a result the high etching rate of more than 350 nm/min, which is more than ten times that of conventional Ar+ ion etching, and relatively smooth surface roughness around 20 nm Ra were achieved with Ar/Cl2/BCl3 mixture using 1.2 kW RF power and -500 V V dc.