Application of mesoporous silica for the oral delivery of poorly water-soluble drugs

The objective of this thesis was to improve the dissolution rate of the poorly waters-soluble drug, fenofibrate by processing it with a high surface area carrier, mesoporous silica. The subsequent properties of the drug – silica composite were studied in terms of drug distribution within the silica matrix, solid state and release properties. Prior to commencing any experimental work, the properties of unprocessed mesoporous silica and fenofibrate were characterised (chapter 3), this allowed for comparison with the processed samples studied in later chapters. Fenofibrate was a highly stable, crystalline drug that did not adsorb moisture, even under long term accelerated storage conditions. It maintained its crystallinity even after SC-CO2 processing. Its dissolution rate was limited and dependent on the characteristics of the particular in vitro media studied. Mesoporous silica had a large surface area and mesopore volume and readily picked up moisture when stored under long term accelerated storage conditions (75% RH, 40 oC). It maintained its mesopore character after SC-CO2 processing. A variety of methods were employed to process fenofibrate with mesoporous silica including physical mixing, melt method, solvent impregnation and novel methods such as liquid and supercritical carbon dioxide (SC-CO2) (chapter 4). It was found that it was important to break down the fenofibrate particulate structure to a molecular state to enable drug molecules enter into the silica mesopores. While all processing methods led to some increase in fenofibrate release properties; the impregnation, liquid and SC-CO2 methods produced the most rapid release rates. SC-CO2 processing was further studied with a view to optimising the processing parameters to achieve the highest drug-loading efficiency possible (chapter 5). In this thesis, it was that SC-CO2 processing pressure had a bearing on drug-loading efficiency. Neither pressure, duration or depressurisation rate affected drug solid state or release properties. The amount of drug that could be loaded onto to the mesoporous silica successfully was also investigated at different ratios of drug mass to silica surface area under constant SC-CO2 conditions; as the drug – silica ratio increased, the drug-loading efficiency decreased, while there was no effect on drug solid state or release properties. The influence of the number of drug-loading steps was investigated (chapter 6) with a view to increasing the drug-loading efficiency. This multiple step approach did not yield an increase in drug-loading efficiency compared to the single step approach. It was also an objective in this chapter to understand how much drug could be loaded into silica mesopores; a method based on the known volume of the mesopores and true density of drug was investigated. However, this approach led to serious repercussions in terms of the subsequent solid state nature of the drug and its release performance; there was significant drug crystallinity and reduced release extent. The impact of in vitro release media on fenofibrate release was also studied (chapter 6). Here it was seen that media containing HCl led to reduced drug release over time compared to equivalent media not containing HCl. The key findings of this thesis are discussed in chapter 7 and included: 1. Drug – silica processing method strongly influenced drug distribution within the silica matrix, drug solid state and release. 2. The silica surface area and mesopore volume also influenced how much drug could be loaded. It was shown that SC-CO2 processing variables such as processing pressure (13.79 – 41.37 MPa), duration time (4 – 24 h) and depressurisation rate (rapid or controlled) did not influence the drug distribution within the SBA- 15 matrix, drug solid state form or release. Possible avenues of research to be considered going forward include the development and application of high resolution imaging techniques to visualise drug molecules within the silica mesopores. Also, the issues surrounding SBA-15 usage in a pharmaceutical manufacturing environment should be addressed.

Embedding colloidal nanoparticles inside mesoporous silica using gas expanded liquids for high loading recyclable catalysts

The ability to tune the structural and chemical properties of colloidal nanoparticles (NPs), make them highly advantageous for studying activity and selectivity dependent catalytic behaviour. Incorporating pre-synthesized colloidal NPs into porous supports materials remains a challenge due to poor wetting and pore permeability. In this report monodisperse, composition controlled AgPd alloy NPs were synthesised and embedded into SBA-15 using supercritical carbon dioxide and hexane. Supercritical fluid impregnation resulted in high metal loading without the requirement for surface pre-treatments. The catalytic activity, reaction profiles and recyclability of the alloy NPs embedded in SBA-15 and immobilised on non-porous SiO2 are evaluated. The NPs incorporated within the SBA-15 porous network showed significantly greater recyclability performance compared to non-porous SiO2.

Experimental impulse radio IEEE 802.15.4a UWB based wireless sensor localization technology: Characterization, reliability and ranging

Ultra Wide Band (UWB) transmission has recently been the object of considerable attention in the field of next generation location aware wireless sensor networks. This is due to its fine time resolution, energy efficient and robustness to interference in harsh environments. This paper presents a thorough applied examination of prototype IEEE 802.15.4a impulse UWB transceiver technology to quantify the effect of line of sight (LOS) and non line of sight (NLOS) ranging in real indoor and outdoor environments. Results included draw on an extensive array of experiments that fully characterize the 802.15.4a UWB transceiver technology, its reliability and ranging capabilities for the first time. A new two way (TW) ranging protocol is proposed. The goal of this work is to validate the technology as a dependable wireless communications mechanism for the subset of sensor network localization applications where reliability and precision positions are key concerns.

Impact of non-optimal grounding of the CC2420 RFIC on a 802.15.4 Tyndall sensor wireless mote

The performance of an RF output matching network is dependent on integrity of the ground connection. If this connection is compromised in anyway, additional parasitic elements may occur that can degrade performance and yield unreliable results. Traditionally, designers measure Constant Wave (CW) power to determine that the RF chain is performing optimally, the device is properly matched and by implication grounded. It is shown that there are situations where modulation quality can be compromised due to poor grounding that is not apparent using CW power measurements alone. The consequence of this is reduced throughput, range and reliability. Measurements are presented on a Tyndall Mote using a CC2420 RFIC todemonstrate how poor solder contact between the ground contacts and the ground layer of the PCB can lead tothe degradation of modulated performance. Detailed evaluation that required the development of a new measurement definition for 802.15.4 and analysis is presented to show how waveform quality is affected while the modulated output power remains within acceptable limits.

Algorithms for indoor localization based on IEEE 802.15.4-2011 UWB and inertial sensors

In this thesis, extensive experiments are firstly conducted to characterize the performance of using the emerging IEEE 802.15.4-2011 ultra wideband (UWB) for indoor localization, and the results demonstrate the accuracy and precision of using time of arrival measurements for ranging applications. A multipath propagation controlling technique is synthesized which considers the relationship between transmit power, transmission range and signal-to-noise ratio. The methodology includes a novel bilateral transmitter output power control algorithm which is demonstrated to be able to stabilize the multipath channel, and enable sub 5cm instant ranging accuracy in line of sight conditions. A fully-coupled architecture is proposed for the localization system using a combination of IEEE 802.15.4-2011 UWB and inertial sensors. This architecture not only implements the position estimation of the object by fusing the UWB and inertial measurements, but enables the nodes in the localization network to mutually share positional and other useful information via the UWB channel. The hybrid system has been demonstrated to be capable of simultaneous local-positioning and remote-tracking of the mobile object. Three fusion algorithms for relative position estimation are proposed, including internal navigation system (INS), INS with UWB ranging correction, and orientation plus ranging. Experimental results show that the INS with UWB correction algorithm achieves an average position accuracy of 0.1883m, and gets 83% and 62% improvements on the accuracy of the INS (1.0994m) and the existing extended Kalman filter tracking algorithm (0.5m), respectively.