Novel formulation strategies for the fabrication of lyophilised orally disintegrating tablets

Orally disintegrating Tablets (ODTs), also known as fast-disintegrating, fast-melt or fast-dissolving tablets, are a relatively novel dosage technology that involves the rapid disintegration or dissolution of the dosage form into a solution or suspension in the mouth without the need for water. The solution containing the active ingredients is swallowed, and the active ingredients are then absorbed through the gastrointestinal epithelium to reach the target and produce the desired effect. Formulation of ODTs was originally developed to address swallowing difficulties of conventional solid oral dosage forms (tablets and capsules) experienced by wide range of patient population, especially children and elderly. The current work investigates the formulation and development of ODTs prepared by freeze drying. Initial studies focused on formulation parameters that influence the manufacturing process and performance of lyophilised tablets based on excipients used in commercial products (gelatin and saccharides). The second phase of the work was followed up by comprehensive studies to address the essential need to create saccharide free ODTs using naturally accruing amino acids individually or in combinations. Furthermore, a factorial design study was carried out to investigate the feasibility of delivering multiparticulate systems of challenging drugs using a novel formulation that exploited the electrostatic associative interaction between gelatin and carrageenan. Finally, studies aimed to replace gelatin with ethically and morally accepted components to the end users were performed and the selected binder was used in factorial design studies to investigate and optimise ODT formulations that incorporated drugs with varies physicochemical properties. Our results show that formulation of elegant lyophilised ODTs with instant disintegration and adequate mechanical strength requires carful optimisation of gelatin concentration and bloom strength in addition to saccharide type and concentration. Successful formulation of saccharides free lyophilised ODTs requires amino acids that crystallise in the frozen state or display relatively high Tg', interact and integrate completely with the binder and, also, display short wetting time with the disintegrating medium. The use of an optimised mixture of gelatin, carrageenan and alanine was able to create viscous solutions to suspend multiparticulate systems and at the same time provide tablets with short disintegration times and adequate mechanical properties. On the other hand, gum arabic showed an outstanding potential for use as a binder in the formulation of lyophilised ODTs. Compared to gelatin formulations, the use of gum arabic simplified the formulation stages, shortened the freeze drying cycles and produced tablets with superior performance in terms of the disintegration time and mechanical strength. Furthermore, formulation of lyophilised ODTs based on gum arabic showed capability to deliver diverse range of drugs with advantages over commercial products.

Design and fabrication of a nonlinear micro impact oscillator

In this paper we describe the design and fabrication of a mechanical autonomous impact oscillator with a MEMS resonator as the frequency control element. The design has been developed with scalability to large 2-D arrays of coupled oscillators in mind. The dynamic behaviour of the impact oscillator was numerically studied and it was found that the geometry nonlinearity has an effect on the static pull-in voltage and equilibrium position. The external driving power can alter the frequency of the impact oscillator. The autonomous nature of the oscillator simplifies the complexity of the drive circuitry and is essential for large 2-D arrays.

The microstructure of the Irish stock market

This is the first paper to examine the microstructure of the Irish Stock Market empirically and is motivated by the adoption, on June 7th of Xetra the modern pan European auction trading system. Prior to this the exchange utilized an antiquated floor based system. This change was an important event for the market as a rich literature exists to suggest that the trading system exerts a strong influence over the behavior of security returns. We apply the ICSS algorithm of Inclan and Tiao (1994) to discover whether the change to the trading system caused a shift in unconditional volatility at the time Xetra was introduced. Because the trading mechanism can influence volatility in a number of ways we also estimate the partial adjustment coefficients of the Amihud and Mendelson (1987) model prior and subsequent to the introduction of Xetra. Although we find no evidence of volatility changes associated with the introduction of Xetra we do find evidence of an increase in the speed of adjustment (JEL: G15).

Advanced UV inscribed fibre grating structures and applications in optical sensing and laser systems

This thesis presents detailed investigation of UV inscribed fibre grating based devices and novel developments in the applications of such devices in optical sensing and fibre laser systems. The major contribution of this PhD programme includes the systematic study on fabrication, spectral characteristics and applications of different types of UV written in-fibre gratings such as Type I and IA Fibre Bragg Gratings (FBGs), Chirped Fibre Bragg Gratings (CFBGs) and Tilted Fibre Gratings (TFGs) with small, large and 45º tilted structures inscribed in normal silica fibre. Three fabrication techniques including holographic, phase-mask and blank beam exposure scanning, which were employed to fabricate a range of gratings in standard single mode fibre, are fully discussed. The thesis reports the creation of smart structures with self-sensing capability by embedding FBG-array sensors in Al matrix composite. In another part of this study, we have demonstrated the particular significant improvements made in sensitising standard FBGs to the chemical surrounding medium by inducing microstructure to the grating by femtosecond (fs) patterning assisted chemical etching technique. Also, a major work is presented for the investigation on the structures, inscription methods and spectral Polarisation Dependent Loss (PDL) and thermal characteristics of different angle TFGs. Finally, a very novel application in realising stable single polarisation and multiwavelength switchable Erbium Doped Fibre Lasers (EDFLs) using intracavity polarisation selective filters based on TFG devices with tilted structures at small, large and exact 45° angles forms another important contribution of this thesis.

Design and fabrication of fibre Bragg gratings with V-shaped dispersion profile for multi-channel signal processing

We have designed and fabricated a new type of fibre Bragg grating (FBG) with a V-shaped dispersion profile for multi-channel dispersion compensation in communication links.

Design and fabrication of fiber Bragg gratings with V-shaped dispersion profile

We propose a new type of fiber Bragg grating (FBG) with a V-shaped dispersion profile. We demonstrate that such V-shaped FBGs bring advantages in manipulation of optical signals compared to conventional FBGs with a constant dispersion, e.g., they can produce larger chirp for the same input pulsewidth and/or can be used as pulse shapers. Application of the proposed V-shaped FBGs for signal prechirping in fiber transmission is examined. The proposed design of the V-shaped FBG can be easily extended to embrace multichannel devices.

Fabrication and application of short and novel structure in-fibre Bragg gratings

This thesis presents details on progress made in the fabrication and application of short and novel structure fibre Bragg gratings. The basic theoretical concepts of in-fibre Bragg gratings and photosensitive mechanisms are introduced together with an overview of fabrication methods and applications presented to date. The fabrication of fibre Bragg gratings using a quadrupled Nd:YAG laser is presented and some of the issues of grating fabrication using a fabrication using a phasemask are investigated, including the variation of the separation of the fibre and phasemask, and other alignment issues. A new apodisation technique is presented, enabling the production of gratings with a wide range of spectral profiles. The technique is used to investigate the design and fabrication of length limited fibre Bragg gratings for use in telecommunication systems as filters. Application to devices designed for use in WDM systems is presented. The use of fibre Bragg gratings as high spatial resolution distributed sensors is investigated. Grating sensing arrays comprising very short apodised gratings are demonstrated and Chirped Moiré gratings are implemented as distributed sensors achieving high spatial resolution with miniature point sensing sub-elements. A novel grating sensing element designed to imitate an interferometer is also presented. Finally, the behaviour of gratings fabricated in Boron-Germania-co-doped fibre is investigated, revealing atypical behaviour of the Bragg wavelength during ageing.

Advanced Fibre Bragg Grating fabrication systems and devices

This thesis address the creation of fibre Bragg grating based sensors and the fabrication systems which are used to manufacture them. The information is presented primarily with experimental evidence, backed up with the current theoretical concepts. The issues involved in fabricating high quality fibre Bragg gratings are systematically investigated. Sources of errors in the manufacturing processes are detected, analysed and reduced to allow higher quality gratings to be fabricated. The use of chirped Moiré gratings as distributed sensors is explored, the spatial resolution is increased beyond that of any previous work and the use of the gratings as distributed load sensors is also presented. Chirped fibre Bragg gratings are shown to be capable of operating as in-situ wear sensors, capable of accurately measuring the wear or erosion of the surface of a material. Two methods of measuring the wear are compared, giving a comparison between an expensive high resolution method and a cheap lower resolution method. The wear sensor is also shown to be capable of measuring the physical size and location of damage induced on the surface of a material. An array method is demonstrated to provide a high survivability such that the array may be damaged yet operate with minimal degradation in performance.

Fabrication and applications of fibre Bragg gratings

The consequences of fabricating Bragg gratings in various fibres, with or without hydrogen loading, and with varying laser power levels are explored. Three new techniques for fabricating chirped gratings are presented. Beams with dissimilar wavefront curvatures are interfered to give chirped gratings. With the same aim techniques of writing gratings on tapered fibres and on deformed fibres are also covered. With these techniques, a wide variety of gratings has been fabricated from the 'superbroad' (with bandwidths of up to 180 nm), small to medium bandwidth gratings with linear chirp profiles and quadratic chirped gratings. It is demonstrated that chirped grating can be concatenated to form all-fibre Fabry-Perot and Moiré resonators. These are further concatenated with chirped gratings to produce filters with narrow passbands and very broad stopbands. A number of other applications are also addressed. The use of chirped fibre gratings for dispersion compensation and femtosecond chirped pulse amplification is demonstrated. Chirped gratings are used as dispersive elements in modelocked fibre lasers producing ultrashort pulses. A chirped fibre grating Fabry-Perot transmission filter is used in a continuous wave laser that exhibits eleven simultaneously lasing wavelengths. Finally, the use of grating-coupler devices as variable reflectivity mirrors for laser optimisation and gain clamping is considered.

Fabrication of micro-channels in optical fibers using femtosecond laser pulses and selective chemical etching

The fabrication of micro-channels in single-mode optical fibers is demonstrated using focused femtosecond laser processing and chemical etching. Straight line micro-channels are achieved based on a simple technique which overcomes limitations imposed by the fiber curved surface.

The microstructure of the foreign exchange market:the determinants of bid-ask spreads in the foreign exchange market

The purpose of this thesis is to shed more light in the FX market microstructure by examining the determinants of bid-ask spread for three currencies pairs, the US dollar/Japanese yen, the British pound/US dollar and the Euro/US dollar in different time zones. I examine the commonality in liquidity with the elaboration of FX market microstructure variables in financial centres across the world (New York, London, Tokyo) based on the quotes of three exchange rate currency pairs over a ten-year period. I use GARCH (1,1) specifications, ICSS algorithm, and vector autoregression analysis to examine the effect of trading activity, exchange rate volatility and inventory holding costs on both quoted and relative spreads. ICSS algorithm results show that intraday spread series are much less volatile compared to the intraday exchange rate series as the number of change points obtained from ICSS algorithm is considerably lower. GARCH (1,1) estimation results of daily and intraday bid-ask spreads, show that the explanatory variables work better when I use higher frequency data (intraday results) however, their explanatory power is significantly lower compared to the results based on the daily sample. This suggests that although daily spreads and intraday spreads have some common determinants there are other factors that determine the behaviour of spreads at high frequencies. VAR results show that there are some differences in the behaviour of the variables at high frequencies compared to the results from the daily sample. A shock in the number of quote revisions has more effect on the spread when short term trading intervals are considered (intra-day) compared to its own shocks. When longer trading intervals are considered (daily) then the shocks in the spread have more effect on the future spread. In other words, trading activity is more informative about the future spread when intra-day trading is considered while past spread is more informative about the future spread when daily trading is considered

3D reconstruction of complex dielectric function of the glass during the femtosecond micro-fabrication

We measure complex amplitude of scattered wave in the far field, and justify theoretically and numerically solution of the inverse scattering problem. This allows single-shot reconstructing of dielectric function distribution during direct femtosecond laser micro-fabrication.