Loading of itraconazole into porous silica and silicon microparticles: characterization and dissolution tests

Most new drug molecules discovered today suffer from poor bioavailability. Poor oral bioavailability results mainly from poor dissolution properties of hydrophobic drug molecules, because the drug dissolution is often the rate-limiting event of the drug’s absorption through the intestinal wall into the systemic circulation. During the last few years, the use of mesoporous silica and silicon particles as oral drug delivery vehicles has been widely studied, and there have been promising results of their suitability to enhance the physicochemical properties of poorly soluble drug molecules. Mesoporous silica and silicon particles can be used to enhance the solubility and dissolution rate of a drug by incorporating the drug inside the pores, which are only a few times larger than the drug molecules, and thus, breaking the crystalline structure into a disordered, amorphous form with better dissolution properties. Also, the high surface area of the mesoporous particles improves the dissolution rate of the incorporated drug. In addition, the mesoporous materials can also enhance the permeability of large, hydrophilic drug substances across biological barriers. T he loading process of drugs into silica and silicon mesopores is mainly based on the adsorption of drug molecules from a loading solution into the silica or silicon pore walls. There are several factors that affect the loading process: the surface area, the pore size, the total pore volume, the pore geometry and surface chemistry of the mesoporous material, as well as the chemical nature of the drugs and the solvents. Furthermore, both the pore and the surface structure of the particles also affect the drug release kinetics. In this study, the loading of itraconazole into mesoporous silica (Syloid AL-1 and Syloid 244) and silicon (TOPSi and TCPSi) microparticles was studied, as well as the release of itraconazole from the microparticles and its stability after loading. Itraconazole was selected for this study because of its highly hydrophobic and poorly soluble nature. Different mesoporous materials with different surface structures, pore volumes and surface areas were selected in order to evaluate the structural effect of the particles on the loading degree and dissolution behaviour of the drug using different loading parameters. The loaded particles were characterized with various analytical methods, and the drug release from the particles was assessed by in vitro dissolution tests. The results showed that the loaded drug was apparently in amorphous form after loading, and that the loading process did not alter the chemical structure of the silica or silicon surface. Both the mesoporous silica and silicon microparticles enhanced the solubility and dissolution rate of itraconazole. Moreover, the physicochemical properties of the particles and the loading procedure were shown to have an effect on the drug loading efficiency and drug release kinetics. Finally, the mesoporous silicon particles loaded with itraconazole were found to be unstable under stressed conditions (at 38 qC and 70 % relative humidity).

Breakdown in p‐n junction diodes made on polycrystalline silicon of large grain size

This communication describes the voltage‐current characteristics in the breakdown region of p‐n junctions made on polycrystalline silicon of large grain size. The observed soft breakdown characteristics have been explained by taking into account the effect of curvature of the junction near the grain boundaries.

Surface Structures of Silicon and Germanium

Si and Ge were cleaved on the (111) plane under ultra high vacuum and exposed to O and subsequent heat treatment. LEED and spot photometric measurements were taken. Cleaved surfaces for both Si and Ge gave the expected (2 x 1) structure. Results for O exposure were qualitatively for Si and Ge. The 1/2 orders disappeared after exposure to approx = 10 exp - exp 7. Integral orders started to weaken at 10 exp -6 to 10 exp - exp 2 torr min., disappearing at 10 exp -1 torr min. Heat treatment of Si at 900 deg C for several seconds restored the integral orders and further heating gave a new pattern with 1/3 orders. Exposure to 2 x 10 exp -6 torr min O without further heating weakened the fractional orders and at 10 exp -5 torr min they disappeared. Integral orders remained after further heating in O. For Ge integral orders were not restored after 0 exposure until heat treatment had continued at 550 deg C for several min. The (1 x 1) structure disappeared after heating at 590 deg C in 7 x 10 exp -1 torr O and further heating at 590 deg C without O restored the integral order Variations of intensity with voltage were measured for the (00) and (20) spots. The results supported a model proposed by Haneman (Phys. Rev., 1968, 170, 705) involving two kinds of atom sites on the cleaved surface. 20 ref.--E.J.S.

I–U Characteristics of MOS Structures on Polycrystalline Silicon

Current-voltage (I–U) characteristics of MOS structures on polycrystalline silicon are investigated. A model based on the carrier transport through the traps in the oxide is described to explain the I–U characteristics.Es werden Strom-Spannungs(I–U)-Charakteristiken von MOS-Strukturen auf polykristallinem Silizium untersucht. Ein Modell zur Erklärung der I–U-Charakteristiken wird beschrieben, das auf dem Ladungstransport über Oxidtraps beruht.

Impedance‐frequency characteristics of metal‐oxide‐semiconductor structures on polycrystalline silicon

This paper reports the variations in impedance with frequency of metal‐oxide‐semiconductor (MOS) structures on polycrystalline silicon. The origin of these impedance‐frequency characteristics are qualitatively explained. These characteristics indicate that the MOS structure on polycrystalline silicon can be exploited to realize voltage controlled filters.

Position-sensitive silicon strip detector characterization using particle beams

Silicon strip detectors are fast, cost-effective and have an excellent spatial resolution. They are widely used in many high-energy physics experiments. Modern high energy physics experiments impose harsh operation conditions on the detectors, e.g., of LHC experiments. The high radiation doses cause the detectors to eventually fail as a result of excessive radiation damage. This has led to a need to study radiation tolerance using various techniques. At the same time, a need to operate sensors approaching the end their lifetimes has arisen. The goal of this work is to demonstrate that novel detectors can survive the environment that is foreseen for future high-energy physics experiments. To reach this goal, measurement apparatuses are built. The devices are then used to measure the properties of irradiated detectors. The measurement data are analyzed, and conclusions are drawn. Three measurement apparatuses built as a part of this work are described: two telescopes measuring the tracks of the beam of a particle accelerator and one telescope measuring the tracks of cosmic particles. The telescopes comprise layers of reference detectors providing the reference track, slots for the devices under test, the supporting mechanics, electronics, software, and the trigger system. All three devices work. The differences between these devices are discussed. The reconstruction of the reference tracks and analysis of the device under test are presented. Traditionally, silicon detectors have produced a very clear response to the particles being measured. In the case of detectors nearing the end of their lifefimes, this is no longer true. A new method benefitting from the reference tracks to form clusters is presented. The method provides less biased results compared to the traditional analysis, especially when studying the response of heavily irradiated detectors. Means to avoid false results in demonstrating the particle-finding capabilities of a detector are also discussed. The devices and analysis methods are primarily used to study strip detectors made of Magnetic Czochralski silicon. The detectors studied were irradiated to various fluences prior to measurement. The results show that Magnetic Czochralski silicon has a good radiation tolerance and is suitable for future high-energy physics experiments.

Neutralization of phosphorus in polycrystalline silicon by hydrogenation

Experimental evidence that phosphorus in silicon is neutralized by hydrogenation is presented by measuring changes in sheet resistance and Hall mobility carrier in heavily phosphorus‐doped polycrystalline films.

Coplanar Capacitively Coupled Probe Fed Microstrip Antennas for Wideband Applications

The design and analysis of a coplanar capacitive fed microstrip antenna suspended above the ground plane is presented. It is demonstrated that the proposed approach can be used for designing antennas with impedance bandwidth of about 50% and a good gain to operate in various microwave bands. The model of the antenna incorporates the capacitive feed strip which is fed by a coaxial probe using equivalent circuit approach, and matches simulation and experimental results. The capacitive feed strip used here is basically a rectangular microstrip capacitor formed from a truncated microstrip transmission line and all its open ends are represented by terminal or edge capacitances. The error analysis was carried out for validity of the model for different design parameters. The antenna configuration can be used where unidirectional radiation patterns are required over a wide bandwidth.

Nanomechanical properties of silicon surfaces nanostructured by excimer laser

Excimer laser irradiation at ambient temperature has been employed to produce nanostructured silicon surfaces. Nanoindentation was used to investigate the nanomechanical properties of the deformed surfaces as a function of laser parameters, such as the angle of incidence and number of laser pulses at a fixed laser fluence of 5 J cm(-2). A single-crystal silicon 311] surface was severely damaged by laser irradiation and became nanocrystalline with an enhanced porosity. The resulting laser-treated surface consisted of nanometer-sized particles. The pore size was controlled by adjusting the angle of incidence and the number of laser pulses, and varied from nanometers to microns. The extent of nanocrystallinity was large for the surfaces irradiated at a small angle of incidence and by a high number of pulses, as confirmed by x-ray diffraction and Raman spectroscopy. The angle of incidence had a stronger effect on the structure and nanomechanical properties than the number of laser pulses.

Effect of magnesium addition and heat treatment on mild wear of hypoeutectic aluminium-silicon alloys

The effect of magnesium addition and subsequent heat treatment on mild wear of a cast hypoeutectic aluminium-silicon alloy when slid against EN 24 steel is studied. Morphology and chemistry of worn surface and subsurface are studied with a view to identify wear mechanism. Stability of an iron-aluminium mixed surface layer was found to be the key factor controlling wear resistance.

Experimental investigation of three-layer electromagnetically coupled circular microstrip antennas

The broadband behaviour of a three-layer electromagnetically coupled circular microstrip antenna is investigated experimentally. The effects of interlayer spacings and the thickness of the parasitic layers on the impedance bandwidth, 3 dB beamwidth and pattern shape, are studied. Experiments show that this structure can provide a frequency bandwidth as high as 20% with a low crosspolarisation level and a moderately high gain.