Methods in general model localization

The aim of this study was to evaluate and test methods which could improve local estimates of a general model fitted to a large area. In the first three studies, the intention was to divide the study area into sub-areas that were as homogeneous as possible according to the residuals of the general model, and in the fourth study, the localization was based on the local neighbourhood. According to spatial autocorrelation (SA), points closer together in space are more likely to be similar than those that are farther apart. Local indicators of SA (LISAs) test the similarity of data clusters. A LISA was calculated for every observation in the dataset, and together with the spatial position and residual of the global model, the data were segmented using two different methods: classification and regression trees (CART) and the multiresolution segmentation algorithm (MS) of the eCognition software. The general model was then re-fitted (localized) to the formed sub-areas. In kriging, the SA is modelled with a variogram, and the spatial correlation is a function of the distance (and direction) between the observation and the point of calculation. A general trend is corrected with the residual information of the neighbourhood, whose size is controlled by the number of the nearest neighbours. Nearness is measured as Euclidian distance. With all methods, the root mean square errors (RMSEs) were lower, but with the methods that segmented the study area, the deviance in single localized RMSEs was wide. Therefore, an element capable of controlling the division or localization should be included in the segmentation-localization process. Kriging, on the other hand, provided stable estimates when the number of neighbours was sufficient (over 30), thus offering the best potential for further studies. Even CART could be combined with kriging or non-parametric methods, such as most similar neighbours (MSN).

High-frequency capacitance-voltage characteristics of amorphous (undoped)/crystalline silicon heterostructures

A numerical procedure is presented for calculating high-frequency capacitance variation with bias in amorphous (undoped)/crystalline silicon heterojunction. The results of the model calculations using this procedure have been reported, for different p silicon substrates. These have been compared with the corresponding capacitance variations in the other limiting case, in which the heterostructure acts like an MIS structure. The effect of interface states on the capacitance characteristics has also been studied. In the second part, we report the results of 1 MHz capacitance measurements on various amorphous (undoped)/crystalline silicon heterostructures.

Mesoporous silica- and silicon-based materials as carriers for poorly water soluble drugs

New chemical entities with unfavorable water solubility properties are continuously emerging in drug discovery. Without pharmaceutical manipulations inefficient concentrations of these drugs in the systemic circulation are probable. Typically, in order to be absorbed from the gastrointestinal tract, the drug has to be dissolved. Several methods have been developed to improve the dissolution of poorly soluble drugs. In this study, the applicability of different types of mesoporous (pore diameters between 2 and 50 nm) silicon- and silica-based materials as pharmaceutical carriers for poorly water soluble drugs was evaluated. Thermally oxidized and carbonized mesoporous silicon materials, ordered mesoporous silicas MCM-41 and SBA-15, and non-treated mesoporous silicon and silica gel were assessed in the experiments. The characteristic properties of these materials are the narrow pore diameters and the large surface areas up to over 900 m²/g. Loading of poorly water soluble drugs into these pores restricts their crystallization, and thus, improves drug dissolution from the materials as compared to the bulk drug molecules. In addition, the wide surface area provides possibilities for interactions between the loaded substance and the carrier particle, allowing the stabilization of the system. Ibuprofen, indomethacin and furosemide were selected as poorly soluble model drugs in this study. Their solubilities are strongly pH-dependent and the poorest (< 100 µg/ml) at low pH values. The pharmaceutical performance of the studied materials was evaluated by several methods. In this work, drug loading was performed successfully using rotavapor and fluid bed equipment in a larger scale and in a more efficient manner than with the commonly used immersion methods. It was shown that several carrier particle properties, in particular the pore diameter, affect the loading efficiency (typically ~25-40 w-%) and the release rate of the drug from the mesoporous carriers. A wide pore diameter provided easier loading and faster release of the drug. The ordering and length of the pores also affected the efficiency of the drug diffusion. However, these properties can also compensate the effects of each other. The surface treatment of porous silicon was important in stabilizing the system, as the non-treated mesoporous silicon was easily oxidized at room temperature. Different surface chemical treatments changed the hydrophilicity of the porous silicon materials and also the potential interactions between the loaded drug and the particle, which further affected the drug release properties. In all of the studies, it was demonstrated that loading into mesoporous silicon and silica materials improved the dissolution of the poorly soluble drugs as compared to the corresponding bulk compounds (e.g. after 30 min ~2-7 times more drug was dissolved depending on the materials). The release profile of the loaded substances remained similar also after 3 months of storage at 30°C/56% RH. The thermally carbonized mesoporous silicon did not compromise the Caco-2 monolayer integrity in the permeation studies and improved drug permeability was observed. The loaded mesoporous silica materials were also successfully compressed into tablets without compromising their characteristic structural and drug releasing properties. The results of this research indicated that mesoporous silicon/silica-based materials are promising materials to improve the dissolution of poorly water soluble drugs. Their feasibility in pharmaceutical laboratory scale processes was also confirmed in this thesis.