Jekaterina Kozlova

Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs.

Electrospinning was introduced as a novel technique for preparing controlled-release (CR) amorphous solid dispersions (SD) and polymeric nanofibers of a poorly water-soluble drug. Piroxicam (PRX) was used as a low-dose poorly-soluble drug and hydroxypropyl methylcellulose (HPMC) as an amorphous-state stabilising carrier polymer in nanofibers. Raman spectroscopy, X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used in the physical characterisation of the CR-SD nanofibers. Special attention was paid on the effects of a polymer and solvent system on the solid-state properties and physical stability of nanofibers. The average dry diameter of the electrospun CR-SD nanofibers ranged from 400 to 600 nm (SEM). PRX existed in amorphous form in the nanofibers immediately after fabrication and after a short-term (3-month) aging at low temperature (6-8 °C/0% RH) and ambient room temperature (22 °C/0% RH). At higher temperature and humidity (30 °C/85% RH), however, amorphous PRX in the nanofibers tended to slowly recrystallise to PRX form III. The electrospun CR-SD nanofibers exhibited a short lag-time, the absence of initial burst release and zero-order linear CR dissolution kinetics. In conclusion, electrospinning can be used to fabricate supersaturating CR-SD nanofibers of PRX and HPMC, and to stabilise the amorphous state of PRX.

Atomic layer deposition of HfO2 on graphene from HfCl4 and H2O

Atomic layer deposition of HfO2 on unmodified graphene from HfCl4 and H2O was investigated. Surface RMS roughness down to 0.5 nm was obtained for amorphous, 30 nm thick hafnia film grown at 180°C. HfO2 was also deposited in a two-step temperature process where the initial growth of about 1 nm at 170°C was continued up to 10–30 nm at 300°C. This process yielded uniform, monoclinic HfO2 films with RMS roughness of 1.7 nm for 10–12 nm thick films and 2.5 nm for 30 nm thick films. Raman spectroscopy studies revealed that the deposition process caused compressive biaxial strain in graphene, whereas no extra defects were generated. An 11 nm thick HfO2 film deposited onto bilayer graphene reduced the electron mobility by less than 10% at the Dirac point and by 30–40% far away from it.

Water-mediated solid-state transformation of a polymorphic drug during aqueous-based drug-layer coating of pellets

During aqueous drug-layer coating, drug substance(s) are exposed to water and elevated temperatures which can lead to water-mediated process induced transformations (PITs). The effects of aqueous drug-layer coating of pellets (Cellets(®)) on the anhydrous piroxicam, PRX, were investigated in the miniaturized coating equipment and with free films. Hydroxypropyl methylcellulose (HPMC) was used as a carrier coating polymer. Free films were prepared by using an in-house small-scale rotating plate system equipped with an atomization air nozzle. Raman spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the solid-state properties and surface morphology of the pellets and free films. The results showed that anhydrous PRX form I (AH) and monohydrate (MH) were stable during drug-layer coating, but amorphous PRX in solid dispersion (SD) crystallized as MH already after 10 min of coating. Furthermore, the increase in a dissolution rate was achieved from the drug-layer coated inert pellets compared to powder forms. In conclusion, water-mediated solid-state PITs of amorphous PRX is evident during aqueous-based drug-layer coating of pellets, and solid-state change can be verified using Raman spectroscopy.

Atomic Layer Deposition and Characterization of Erbium Oxide-Doped Zirconium Oxide Thin Films

ZrO 2 films doped with Er 2 O 3 were grown by atomic layer deposition from tris(2,2,6,6-tetramethyl-3,5-heptanedionato)erbium, bis(methylcyclopentadienyl)methoxymethylzirconium, and ozone as precursors at 350°C. The erbium content was 1―5 cation %. The films were uniform in thickness. The ZrO 2 :Er 2 O 3 films were crystallized already in the as-deposited state. Upon annealing at 650°C, they were stabilized in the form of cubic or tetragonal polymorph of ZrO 2 . Enhancement in capacitance required intense crystallization that was observed when the film thickness exceeded 4.4 nm. The permittivity of the ZrO 2 :Er 2 O 3 films could reach 31. The capacitors based on the doped ZrO 2 possessed lower capacitance equivalent oxide thickness compared to the nondoped ZrO 2 and also comparable leakage current densities.

Nanometer depth resolution in 3D topographic analysis of drug-loaded nanofibrous mats without sample preparation.

We showed that scanning white light interferometry (SWLI) can provide nanometer depth resolution in 3D topographic analysis of electrospun drug-loaded nanofibrous mats without sample preparation. The method permits rapidly investigating geometric properties (e.g. fiber diameter, orientation and morphology) and surface topography of drug-loaded nanofibers and nanomats. Electrospun nanofibers of a model drug, piroxicam (PRX), and hydroxypropyl methylcellulose (HPMC) were imaged. Scanning electron microscopy (SEM) served as a reference method. SWLI 3D images featuring 29 nm by 29 nm active pixel size were obtained of a 55 μm × 40 μm area. The thickness of the drug-loaded non-woven nanomats was uniform, ranging from 2.0 μm to 3.0 μm (SWLI), and independent of the ratio between HPMC and PRX. The average diameters (n=100, SEM) for drug-loaded nanofibers were 387 ± 125 nm (HPMC and PRX 1:1), 407 ± 144 nm (HPMC and PRX 1:2), and 290 ± 100 nm (HPMC and PRX 1:4). We found advantages and limitations in both techniques. SWLI permits rapid non-contacting and non-destructive characterization of layer orientation, layer thickness, porosity, and surface morphology of electrospun drug-loaded nanofibers and nanomats. Such analysis is important because the surface topography affects the performance of nanomats in pharmaceutical and biomedical applications.

Atomic layer deposition of aluminum oxide films on graphene

Seed-layer approach was studied to initiate atomic layer deposition (ALD) of Al2O3 films on graphene. Low-temperature ALD and electron beam evaporation (EBE) were applied for seed-layer preparation before deposition of the dielectric at 200 °C using trimethyl-aluminum and water or ozone as precursors. To characterize nucleation of the films and possible influence of the ALD processes on the quality of graphene, properties of graphene and Al2O3 films were investigated by Raman spectroscopy, X-ray fluorescence and X-ray photoelectron spectroscopy methods. The results suggest that seed layer formation by low-temperature ALD was more efficient in the O3-based process than in the H2O-based one while EBE seed layer provided fastest growth of Al2O3 together with minimum incubation period.

Atomic Layer Deposition of High-k Oxides on Graphene

Graphene that is a single hexagonal layer of carbon atoms with very high intrinsic charge carrier mobility (more than 200 000 cm2/Vs at 4.2 K for suspended samples; Bolotin, et al., 2008) attracts attention as a promising material for future nanoelectronics. During last few years, significant advancement has been made in preparation of large-area graphene. The lateral sizes of substrates for graphene layers have been increased up to 3⁄4 m (Bae et al., 2010) and continuous roll-to-roll deposition of graphene has been published (Hesjedal, 2011). This kind of progress might allow one to apply similar planar technologies for fabricating graphene-based devices in future as currently used for processing of siliconbased structures. After very first experiments (Novoselov et al., 2004), in which the electrical properties of isolated graphene sheets were characterized, a lot of attention has been paid to the similar studies, i.e. investigation of uncovered graphene flakes deposited on oxidized silicon wafers that served as back gates. However, in order to realize graphene-based devices, a highquality dielectric on top of graphene is required for electrostatic gates as well as for tunnel barriers for spin injection. For efficient control of charge carrier movement dielectric layers deposited on graphene should be very thin, a few nanometers thick, and of very uniform thickness without any pinholes. At the same time, the dielectric should possess high dielectric constant, high breakdown voltage and low leakage current even at a small thickness. And, of course, it is expected that the high mobility of charge carriers in graphene should not be markedly affected by the dielectric layer. In order to make top-gated graphene-based Field Effect Transistor (FET), Lemme et al. (2007) applied evaporation techniques for preparation of a gate stack with ~20 nm thick SiO2 dielectric layer on graphene. They used p-type Si(100) wafers with a boron doping concentration of 1015 cm-3, which were oxydized to a SiO2 thickness of 300 nm. On these wafers, micromechanically exfoliated graphene flakes were sticked. The Ti/Au source and drain electrodes were prepared using optical lift-off lithography. Next, electron beam lift-off lithography was applied to define a top gate electrode on top of the graphene flake covered with the dielectric (Fig. 1a). Lemme et al. were first to demonstrate that the combined effect of back and top gates can be applied to graphene devices. However, measurements of the back-gate characteristics before

Dysprosium oxide and dysprosium-oxide-doped titanium oxide thin films grown by atomic layer deposition

Dysprosium oxide and dysprosium-oxide-doped titanium oxide thin films were grown by atomic layer deposition on silicon substrates. For depositing dysprosium and titanium oxides Dy(thd)3-O3 and TiCl4-O3 were used as precursors combinations. Appropriate parameters for Dy(thd)3-O3 growth process were obtained by using a quartz crystal microbalance system. The Dy2O3 films were deposited on planar substrates and on three-dimensional substrates with aspect ratio 1:20. The Dy/Ti ratio of Dy2O3-doped TiO2 films deposited on a planar silicon substrate ranged from 0.04 to 0.06. Magnetometry studies revealed that saturation of magnetization could not be observed in planar Dy2O3 films, but it was observable in Dy2O3 films on 3D substrates and in doped TiO2 films with a Dy/Ti atomic ratio of 0.06. The latter films exhibited saturation magnetization 10−6 A cm2 and coercivity 11 kA/m at room temperature.

Magnetic and Electrical Performance of Atomic Layer Deposited Iron Erbium Oxide Thin Films

Mixed films of a high-permittivity oxide, Er2O3, and a magnetic material, Fe2O3, were grown by atomic layer deposition on silicon and titanium nitride at 375 °C using erbium diketonate, ferrocene, and ozone as precursors. Crystalline phases of erbium and iron oxides were formed. Growth into three-dimensional trenched structures was demonstrated. A structure deposited using tens to hundreds subsequent cycles for both constituent metal oxide layers promoted both charge polarization and saturative magnetization compared to those in the more homogeneously mixed films.

Atomic Layer Deposition of Zirconium Oxide on Carbon Nanoparticles

In this report we describe preparation of structures containing carbon nanoparticles for potential applications in nonvolatile memories. The carbon nanoparticles were synthesized from 5-methylresorcinol and formaldehyde via base catalysed polycondensation reaction, and were distributed over substrates by dip-coating the substrates into an organic solution. Before deposition of nanoparticles the substrates were covered with 2 nm thick Al2O3 layer grown by atomic layer deposition (ALD) from Al(CH3)3 and O3. After deposition of nanoparticles the samples were coated with ZrO2 films grown from C5H5Zr[N(CH3)2]3 and H2O. Both dielectrics were grown in two-temperature ALD processes starting deposition of Al2O3 at 25 °C and ZrO2 at 200 °C, thereafter completing both processes at a substrate temperature of 300 °C. Deposition of ZrO2 changed the structure of C-nanoparticles, which still remained in a Si/Al2O3/C/ZrO2 structure as a separate layer. Electrical characterization of nanostructures containing Al2O3 as tunnel oxide, C-nanoparticles as charge traps and ZrO2 as control oxide showed hysteretic flat-band voltage shift of about 1V.