Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP

Quantum-confinement effect on holes in silicon nanowires: Relationship between wave function and band structure

The authors theoretically studied the valence band structure and hole effective mass of rectangular cross-sectional Si nanowires (NWs) with the crystal orientation of [110], [111], and [001]. The E–k dispersion and the wave function were calculated using an sp^3d^5s∗ tight-binding method and analyzed with the focus on the nature of p orbitals constituting the subbands. In [110] and [111] nanowires, longitudinal/transverse p orbitals are well separated and longitudinal component makes light (top) subbands and transverse component makes heavy subbands. The heavy subbands are located far below the top light band when NW has square cross-section, but they gain their energy with the increase in the NW width and come near the band edge. This energy shift of heavy bands in [110] NWs shows strong anisotropy to the direction of quantum confinement whereas that in [111] NWs does not have such anisotropy. This anisotropic behavior and the difference among orientations are understandable by the character of the wave function of heavy subbands. Regarding the [001] nanowires, the top valence state is formed by the mixture of longitudinal/transverse p orbitals, which results in heavy effective mass and large susceptibility to lateral-size variation. The correlation of the wave function of hole states between nanowires and bulk is also discussed briefly

Bandgap shift by quantum confinement effect in <100> Si-nanowires derived from threshold-voltage shift of fabricated metal-oxide-semiconductor field effect transistors and theoretical calculations

Si-nanowire (Si-NW) MOSFETs, the cross-sectional size (square root of the cross-sectional area of NWs) of which was changed from 18 to 4 nm, were fabricated and characterized. Both n- and p-channel MOSFETs have shown a nearly ideal subthreshold swing of 63 mV/decade. The threshold voltage of n-/p-channel MOSFETs has gradually increased/decreased with decreasing the cross-sectional size. The bandgap shift from bulk Si has been derived from the threshold-voltage shift. The bandgap of Si-NWs was calculated by a density functional theory, tight binding method, and effective mass approximation. The calculated bandgap shows good agreement with that derived from threshold voltage. The theoretical calculation indicates that the bandgap is dominated by the cross-sectional size (area) and is not very sensitive to the shape within the aspect-ratio range of 1.0-2.5

Mobility oscillation by one-dimensional quantum confinement in Si-nanowire metal-oxide-semiconductor field effect transistors

Si-nanowire p-channel metal-oxide-semiconductor field effect transistors (MOSFETs), in which the typical cross section of the nanowire is a rectangular shape with 3 nm height and 18 nm width, have been fabricated and the current-voltage characteristics have been measured from 101 to 396 K. The transconductance has shown oscillation up to 309 K. The carrier transport has been theoretically analyzed, assuming that the acoustic phonon scattering is dominant. The electronic states have been determined from the effective mass approximation and the mobility from the relaxation time approximation as a function of the Fermi level. Relation between the gate voltage and the Fermi level has been estimated from the MOSFET structure. The calculated mobility has shown the oscillation with change in the Fermi level (the gate voltage), resulting in the transconductance oscillation. The oscillation originates from one-dimensional density of states (∝E−0.5)

The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo

Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2) cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels. The inhibitory action of saxagliptin on the renal DPP-4 activity was retained, even when its inhibitory effect on the plasma DPP-4 activity disappeared. However, the inhibitory action of sitagliptin on the renal DPP-4 activity was abolished in correlation with the inhibition of the plasma DPP-4 activity. In situ staining showed that saxagliptin suppressed the DPP-4 activity in both glomerular and tubular cells and its inhibitory effects were significantly higher than those of sitagliptin. Saxagliptin exerted a sustained inhibitory effect on the renal DPP-4 activity in vitro and in vivo. The long binding action of saxagliptin in renal tubular cells might involve the sustained inhibition of renal DPP-4

The ultrasound-guided nerve blocks of abdominal wall contributed to anesthetic management of cholecystectomy in a patient with Becker muscular dystrophy without using muscle relaxants

Abstract Becker muscular dystrophy (BMD) is a progressive neuromuscular disorder caused by mutations in the dystrophin gene. The sensitivity to non-depolarizing muscle relaxant in a patient with muscle dystrophy is reportedly higher than that in normal individuals, and the duration of the effect is known to be prolonged. In this report, we present the case of a 58-year-old man with BMD who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis under total intravenous anesthesia without the use of muscle-relaxant drugs and supplemented with regional anesthesia. Anesthesia was induced and maintained with propofol, remifentanil, and fentanyl; ultrasound-guided bilateral rectus sheath block (RSB) and right-sided subcostal transversus abdominis plane block (TAP) were performed. The procedure required conversion to open surgery because of hard conglutination; intraoperative and postoperative periods were uneventful. Adequate analgesia was maintained after extubation because of the effect of RSB and TAP