Nickel manganite spinel thin films prepared by chemical solution deposition exhibit negative temperature coefficient of resistance (TCR) values between −3.3 and −4.5%/K. In contrast to bulk thermistors, dense films could be prepared completely within the spinel phase field. Thus, decomposition into the NiO phase and a Mn‐rich spinel, which is problematic in bulk ceramics, is minimized in thin films. For films prepared outside of the single‐phase field, phase separation cannot always be detected using X‐ray diffraction. In such cases, transmission electron microscopy is useful in identifying decomposition. It is found that the lattice parameters for films with compositions ranging between Mn/(Mn+Ni)=0.14 and 0.77 are smaller than the values reported for nickel manganite spinels, suggesting cation deficiency. Single‐phase spinel films are compared with single‐phase bixbyite films synthesized between 630° and 930°C. The bixbyite phase exhibits lower TCR and lower resistivity (TCR=−3.1 to −3.3%/K and resistivity values=400–1600 Ω·cm) compared with spinel (TCR=−3.6 to −4.1%/K and resistivity values=3500–21 000 Ω·cm). Composite films (achieved by controlling the pyrolysis to create a low local pO2 during annealing) show intermediate values (TCR=−3.0 to −3.8%/K and resistivity values=470–6600 Ω·cm).
Single‐phase metastable cubic spinel nickel manganite films, 0.5 ≤ Mn/(Mn+Ni) ≤ 0.8, were produced using chemical solution deposition. Of these, the sample with Mn/(Mn+Ni) = 0.80 showed the lowest electrical resistivity. Films annealed in Argon at 400°C for 5 h exhibit temperature coefficient of resistance values ranging from −3.81 to −3.93%/K and electrical resistivities of ~10 kΩ‐cm. It was found by transmission electron microscopy that the metastable spinel phase appeared in both pyrolyzed and post‐deposition annealed films. Spectroscopic ellipsometry measurements over the spectral range from 0.75 to 6.0 eV showed that the complex dielectric function spectra (ε = ε1 + iε2) varied as a function of the annealing conditions, due at least in part to changes in film density. Aging experiments have been used to identify variations in resistivity and temperature coefficient of resistance as functions of time to assess material stability. As a result, the aging coefficient was 6.5% for a film with Mn/(Ni+Mn) = 0.80 after aging at 150°C for 500 h.
Amitifadine (EB-1010, formerly DOV 21,947) is a serotonin-preferring triple reuptake inhibitor that is a drug candidate for major depressive disorder. We investigated several relevant biopharmaceutic and drug-like characteristics of amitifadine using in vitro methodology and additionally determined the in vivo brain to plasma ratio of the drug in rats. Amitifadine was highly plasma protein bound with over 99% of drug bound to human plasma proteins. Using Caco-2 cell lines, amitifadine was bidirectionally highly permeable and showed no evidence of active secretion. Amitifadine was metabolized slowly by human hepatocytes and the major metabolite was the lactam EB-10101. In vitro studies using human liver microsomes demonstrated that EB-10101 was formed by monoamine oxidase A (MAO-A) and a NADPHdependent enzyme, possibly a cytochrome P450 (CYP) isoform. Amitifadine was a moderate inhibitor of the human isoforms of the major drug metabolizing enzymes CYP2D6, CYP3A4, CYP2C9, and CYP2C19 (IC50 = 9 - 100 μM), but was a potent inhibitor of human CYP2B6 (IC50 = 1.8 μM). The brain to plasma ratio for amitifadine varied from 3.7 - 6.5 at various time points, indicating preferential partitioning into rat brain versus plasma. The low affinity for the major drug metabolizing CYP enzymes and metabolism by multiple pathways may reduce pharmacokinetic drug-drug interactions and effects of enzyme polymorphisms. Overall, these studies suggest that amitifadine has drug-like characteristics favorable for drug development.
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