Mathematical modelling of controlled drug release from polymer micro-spheres : incorporating the effects of swelling, diffusion and dissolution via moving boundary problems

Controlled drug delivery is a key topic in modern pharmacotherapy, where controlled drug delivery devices are required to prolong the period of release, maintain a constant release rate, or release the drug with a predetermined release profile. In the pharmaceutical industry, the development process of a controlled drug delivery device may be facilitated enormously by the mathematical modelling of drug release mechanisms, directly decreasing the number of necessary experiments. Such mathematical modelling is difficult because several mechanisms are involved during the drug release process. The main drug release mechanisms of a controlled release device are based on the device’s physiochemical properties, and include diffusion, swelling and erosion. In this thesis, four controlled drug delivery models are investigated. These four models selectively involve the solvent penetration into the polymeric device, the swelling of the polymer, the polymer erosion and the drug diffusion out of the device but all share two common key features. The first is that the solvent penetration into the polymer causes the transition of the polymer from a glassy state into a rubbery state. The interface between the two states of the polymer is modelled as a moving boundary and the speed of this interface is governed by a kinetic law. The second feature is that drug diffusion only happens in the rubbery region of the polymer, with a nonlinear diffusion coefficient which is dependent on the concentration of solvent. These models are analysed by using both formal asymptotics and numerical computation, where front-fixing methods and the method of lines with finite difference approximations are used to solve these models numerically. This numerical scheme is conservative, accurate and easily implemented to the moving boundary problems and is thoroughly explained in Section 3.2. From the small time asymptotic analysis in Sections 5.3.1, 6.3.1 and 7.2.1, these models exhibit the non-Fickian behaviour referred to as Case II diffusion, and an initial constant rate of drug release which is appealing to the pharmaceutical industry because this indicates zeroorder release. The numerical results of the models qualitatively confirms the experimental behaviour identified in the literature. The knowledge obtained from investigating these models can help to develop more complex multi-layered drug delivery devices in order to achieve sophisticated drug release profiles. A multi-layer matrix tablet, which consists of a number of polymer layers designed to provide sustainable and constant drug release or bimodal drug release, is also discussed in this research. The moving boundary problem describing the solvent penetration into the polymer also arises in melting and freezing problems which have been modelled as the classical onephase Stefan problem. The classical one-phase Stefan problem has unrealistic singularities existed in the problem at the complete melting time. Hence we investigate the effect of including the kinetic undercooling to the melting problem and this problem is called the one-phase Stefan problem with kinetic undercooling. Interestingly we discover the unrealistic singularities existed in the classical one-phase Stefan problem at the complete melting time are regularised and also find out the small time behaviour of the one-phase Stefan problem with kinetic undercooling is different to the classical one-phase Stefan problem from the small time asymptotic analysis in Section 3.3. In the case of melting very small particles, it is known that surface tension effects are important. The effect of including the surface tension to the melting problem for nanoparticles (no kinetic undercooling) has been investigated in the past, however the one-phase Stefan problem with surface tension exhibits finite-time blow-up. Therefore we investigate the effect of including both the surface tension and kinetic undercooling to the melting problem for nanoparticles and find out the the solution continues to exist until complete melting. The investigation of including kinetic undercooling and surface tension to the melting problems reveals more insight into the regularisations of unphysical singularities in the classical one-phase Stefan problem. This investigation gives a better understanding of melting a particle, and contributes to the current body of knowledge related to melting and freezing due to heat conduction.

Membership retention within the sporting industry : factors affecting relationship dissolution

Relationship dissolution has been somewhat ignored in the study of relationship marketing paradigm. While there has been an abundance of literature giving broad conceptualizations on how to master the intricacies of relationships, very little has discussed the concept of relationship dissolution. This is especially true of the sporting industry, which does not yet understand the factors that contribute to members relinquishing their membership and severing relationship ties with the club. Team performance was found to be the most powerful predictor of relationship dissolution; however, both satisfaction with the sportscape and emotional bonds had a significant influence on the decision for a member not to renew their membership. Although team performance is mostly out of the hands of sport marketers, greater focus should be given to implementing strategies that enhance the emotional aspects of the club-member relationship while also improving aspects of the service facility.

Optimal allocation and sizing of capacitors to minimize the transmission line loss and to improve the voltage profile

To allocate and size capacitors in a distribution system, an optimization algorithm, called Discrete Particle Swarm Optimization (DPSO), is employed in this paper. The objective is to minimize the transmission line loss cost plus capacitors cost. During the optimization procedure, the bus voltage, the feeder current and the reactive power flowing back to the source side should be maintained within standard levels. To validate the proposed method, the semi-urban distribution system that is connected to bus 2 of the Roy Billinton Test System (RBTS) is used. This 37-bus distribution system has 22 loads being located in the secondary side of a distribution substation (33/11 kV). Reducing the transmission line loss in a standard system, in which the transmission line loss consists of only about 6.6 percent of total power, the capabilities of the proposed technique are seen to be validated.

Developing a multi-dimensional scale for ethical decision making: the managerial ethical profile (MEP)

This article describes the development and validation of a multi-dimensional scale for measuring managers’ perceptions of the range of factors that routinely guide their decision-making processes. An instrument for identifying managerial ethical profiles (MEP) is developed by measuring the perceived role of different ethical principles in the decision-making of managers. Evidence as to the validity of the multidimensionality of the ethical scale is provided, based on the comparative assessment of different models for managerial ethical decision-making. Confirmatory Factor Analysis (CFA) supported a eight-factor model including two factors for each of the main four schools of moral philosophy. Future research needs and the value of this measure to business ethics are discussed.

Bioactive inorganic materials/alginate composite microspheres with controllable drug-delivery ability

Alginate microspheres are considered a promising material as a drug carrier in bone repair due to excellent biocompatibility, but their main disadvantage is low drug entrapment efficiency and non-controllable release. The aim of this study was to investigate the effect of incorporating mesoporous bioglass (MBG), non-mesoporous bioglass (BG) or hydroxyapatite (HAp) into alginate microspheres on their drug-loading and release properties. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and atomic emission spectroscopy (AES) were used to analyse the composition, structure and dissolution of bioactive inorganic materials and their microspheres. Dexamethasone (DEX)-loading and release ability of four microspheres were tested in phosphate buffered saline with varying pHs. Results showed that the drug-loading capacity was enhanced with the incorporation of bioactive inorganic materials into alginate microspheres. The MBG/Alginate microspheres had the highest drug loading ability. DEX release from alginate microspheres correlated to the dissolution of MBG, BG and HAp in PBS, and that the pH was an efficient factor in controlling the DEX release; a high pH resulted in greater DEX release, whereas a low pH delayed DEX release. In addition, MBG/alginate, BG/alginate and HAp/alginate microspheres had varying apatite-formation and dissolution abilities, which indicate that the composites would behave differently with respect to bioactivity. The study suggests that microspheres made of a composite of bioactive inorganic materials and alginate have a bioactivity and degradation profile which greatly improves their drug delivery capacity, thus enhancing their potential applications as bioactive filler materials for bone tissue regeneration.

Correlating vehicle forces and track profile

A research project was conducted at Queensland University of Technology on the relationship between the forces at the wheel-rail interface in track and the rate of degradation of track. Data for the study was obtained from an instrumented vehicle which ran repeatedly over a section of Queensland Rail's track in Central Queensland over a 6-month period. The wheel-rail forces had to be correlated with the elements of roughness in the test track profile, which were measured with a variety of equipment. At low frequencies, there was strong correlation between forces and profile, as expected, but diminishing correlation as frequencies increased.

Life in the 'real world': a profile of Queensland University of Technology Library and Information Science graduates.

A graduate destination survey can provide a snap shot in time of a graduate’s career progression and outcome. This paper will present the results of a Queensland University of Technology study exploring the employment outcomes of students who had completed a library and information science course from the Faculty of Information Technology between 2000 and 2008. Seventy-four graduates completed an online questionnaire administered in July 2009. The study found that 90% of the graduates surveyed were working and living in Queensland, with over three quarters living and working in Brisbane. Nearly 70% were working full-time, while only 1.4% indicating that they were unemployed and looking for work. Over 80% of the graduates identified themselves as working in “librarianship”. This study is the first step in understanding the progression and destination of QUT’s library and information science graduates. It is recommended that this survey becomes an ongoing initiative so that the results can be analysed and compared over time.