Ultrasound-assisted surface engineering of pharmaceutical powders

Effective processing of powdered particles can facilitate powder handling and result in better drug product performance, which is of great importance in the pharmaceutical industry where the majority of active pharmaceutical ingredients (APIs) are delivered as solid dosage forms. The purpose of this work was to develop a new ultrasound-assisted method for particle surface modification and thin-coating of pharmaceutical powders. The ultrasound was used to produce an aqueous mist with or without a coating agent. By using the proposed technique, it was possible to decrease the interparticular interactions and improve rheological properties of poorly-flowing water-soluble powders by aqueous smoothing of the rough surfaces of irregular particles. In turn, hydrophilic polymer thin-coating of a hydrophobic substance diminished the triboelectrostatic charge transfer and improved the flowability of highly cohesive powder. To determine the coating efficiency of the technique, the bioactive molecule β-galactosidase was layered onto the surface of powdered lactose particles. Enzyme-treated materials were analysed by assaying the quantity of the reaction product generated during enzymatic cleavage of the milk sugar. A near-linear increase in the thickness of the drug layer was obtained during progressive treatment. Using the enzyme coating procedure, it was confirmed that the ultrasound-assisted technique is suitable for processing labile protein materials. In addition, this pre-treatment of milk sugar could be used to improve utilization of lactose-containing formulations for populations suffering from severe lactose intolerance. Furthermore, the applicability of the thin-coating technique for improving homogeneity of low-dose solid dosage forms was shown. The carrier particles coated with API gave rise to uniform distribution of the drug within the powder. The mixture remained homogeneous during further tabletting, whereas the reference physical powder mixture was subject to segregation. In conclusion, ultrasound-assisted surface engineering of pharmaceutical powders can be effective technology for improving formulation and performance of solid dosage forms such as dry powder inhalers (DPI) and direct compression products.

Biocompatibility and biofunctionalization of mesoporous silicon particles

Several of the newly developed drug molecules experience poor biopharmaceutical behavior, which hinders their effective delivery at the proper site of action. Among the several strategies employed in order to overcome this obstacle, mesoporous silicon-based materials have emerged as promising drug carriers due to their ability to improve the dissolution behavior of several poorly water-soluble drugs compounds confined within their pores. In addition to improve the dissolution behavior of the drugs, we report that porous silicon (PSi) nanoparticles have a higher degree of biocompatibility than PSi microparticles in several cell lines studied. In addition, the degradation of the nanoparticles showed its potential to fast clearance in the body. After oral delivery, the PSi particles were also found to transit the intestines without being absorbed. These results constituted the first quantitative analysis of the behavior of orally administered PSi nanoparticles compared with other delivery routes in rats. The self-assemble of a hydrophobin class II (HFBII) protein at the surface of hydrophobic PSi particles endowed the particles with greater biocompatibility in different cell lines, was found to reverse their hydrophobicity and also protected a drug loaded within its pores against premature release at low pH while enabling subsequent drug release as the pH increased. These results highlight the potential of HFBII-coating for PSi-based drug carriers in improving their hydrophilicity, biocompatibility and pH responsiveness in drug delivery applications. In conclusion, mesoporous silicon particles have been shown to be a versatile platform for improving the dissolution behavior of poorly water-soluble drugs with high biocompatibility and easy surface modification. The results of this study also provide information regarding the biofunctionalization of the THCPSi particles with a fungal protein, leading to an improvement in their biocompatibility and endowing them with pH responsive and mucoadhesive properties.

Atomic Layer Deposition and Photocatalytic Properties of Titanium Dioxide Thin Films

Photocatalytic TiO2 thin films can be highly useful in many environments and applications. They can be used as self-cleaning coatings on top of glass, tiles and steel to reduce the amount of fouling on these surfaces. Photocatalytic TiO2 surfaces have antimicrobial properties making them potentially useful in hospitals, bathrooms and many other places where microbes may cause problems. TiO2 photocatalysts can also be used to clean contaminated water and air. Photocatalytic oxidation and reduction reactions proceed on TiO2 surfaces under irradiation of UV light meaning that sunlight and even normal indoor lighting can be utilized. In order to improve the photocatalytic properties of TiO2 materials even further, various modification methods have been explored. Doping with elements such as nitrogen, sulfur and fluorine, and preparation of different kinds of composites are typical approaches that have been employed. Photocatalytic TiO2 nanotubes and other nanostructures are gaining interest as well. Atomic Layer Deposition (ALD) is a chemical gas phase thin film deposition method with strong roots in Finland. This unique modification of the common Chemical Vapor Deposition (CVD) method is based on alternate supply of precursor vapors to the substrate which forces the film growth reactions to proceed only on the surface in a highly controlled manner. ALD gives easy and accurate film thickness control, excellent large area uniformity and unparalleled conformality on complex shaped substrates. These characteristics have recently led to several breakthroughs in microelectronics, nanotechnology and many other areas. In this work, the utilization of ALD to prepare photocatalytic TiO2 thin films was studied in detail. Undoped as well as nitrogen, sulfur and fluorine doped TiO2 thin films were prepared and thoroughly characterized. ALD prepared undoped TiO2 films were shown to exhibit good photocatalytic activities. Of the studied dopants, sulfur and fluorine were identified as much better choices than nitrogen. Nanostructured TiO2 photocatalysts were prepared through template directed deposition on various complex shaped substrates by exploiting the good qualities of ALD. A clear enhancement in the photocatalytic activity was achieved with these nanostructures. Several new ALD processes were also developed in this work. TiO2 processes based on two new titanium precursors, Ti(OMe)4 and TiF4, were shown to exhibit saturative ALD-type of growth when water was used as the other precursor. In addition, TiS2 thin films were prepared for the first time by ALD using TiCl4 and H2S as precursors. Ti1-xNbxOy and Ti1-xTaxOy transparent conducting oxide films were prepared successfully by ALD and post-deposition annealing. Highly unusual, explosive crystallization behaviour occurred in these mixed oxides which resulted in anatase crystals with lateral dimensions over 1000 times the film thickness.

Modelling vacuum arcs : from plasma initiation to surface interactions

A better understanding of vacuum arcs is desirable in many of today's 'big science' projects including linear colliders, fusion devices, and satellite systems. For the Compact Linear Collider (CLIC) design, radio-frequency (RF) breakdowns occurring in accelerating cavities influence efficiency optimisation and cost reduction issues. Studying vacuum arcs both theoretically as well as experimentally under well-defined and reproducible direct-current (DC) conditions is the first step towards exploring RF breakdowns. In this thesis, we have studied Cu DC vacuum arcs with a combination of experiments, a particle-in-cell (PIC) model of the arc plasma, and molecular dynamics (MD) simulations of the subsequent surface damaging mechanism. We have also developed the 2D Arc-PIC code and the physics model incorporated in it, especially for the purpose of modelling the plasma initiation in vacuum arcs. Assuming the presence of a field emitter at the cathode initially, we have identified the conditions for plasma formation and have studied the transitions from field emission stage to a fully developed arc. The 'footing' of the plasma is the cathode spot that supplies the arc continuously with particles; the high-density core of the plasma is located above this cathode spot. Our results have shown that once an arc plasma is initiated, and as long as energy is available, the arc is self-maintaining due to the plasma sheath that ensures enhanced field emission and sputtering. The plasma model can already give an estimate on how the time-to-breakdown changes with the neutral evaporation rate, which is yet to be determined by atomistic simulations. Due to the non-linearity of the problem, we have also performed a code-to-code comparison. The reproducibility of plasma behaviour and time-to-breakdown with independent codes increased confidence in the results presented here. Our MD simulations identified high-flux, high-energy ion bombardment as a possible mechanism forming the early-stage surface damage in vacuum arcs. In this mechanism, sputtering occurs mostly in clusters, as a consequence of overlapping heat spikes. Different-sized experimental and simulated craters were found to be self-similar with a crater depth-to-width ratio of about 0.23 (sim) - 0.26 (exp). Experiments, which we carried out to investigate the energy dependence of DC breakdown properties, point at an intrinsic connection between DC and RF scaling laws and suggest the possibility of accumulative effects influencing the field enhancement factor.