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.

Understanding the operational structure of Southeast Asian drug trafficking groups in Australia

This thesis examined the operational structure of Southeast Asian drug trafficking groups operating on the eastern seaboard of Australia by testing the validity and application of organised crime and drug trafficking typologies using data obtained from 159 drug trafficking cases in three Australian states: New South Wales; Queensland; and Victoria. Key findings indicated that the usefulness of typologies is limited when classifying and analysing organised crime groups. In particular, Southeast Asian drug trafficking groups operated largely in small, informal, family-based hierarchies or groups that were better conceptualised using theoretical perspectives from network and cultural studies. The study recommended that replicating previous empirical research in the field is an effective approach that will contribute towards building a cumulative body of knowledge on organised crime structures.

Enlarged stopping distance to improve vehicle discharge at urban signalised intersections

Normally, vehicles queued at an intersection reach maximum flow rate after the fourth vehicle and results in a start-up lost time. This research demonstrated that the Enlarged Stopping Distance (ESD) concept could assist in reducing the start-up time and therefore increase traffic flow capacity at signalised intersections. In essence ESD gives sufficient space for a queuing vehicle to accelerate simultaneously without having to wait for the front vehicle to depart, hence reducing start-up lost time. In practice, the ESD concept would be most effective when enlarged stopping distance between the first and second vehicle allowing faster clearance of the intersection.

Youth Alcohol and Drug Practice Guide 3 : Practice Strategies and Interventions

This guide canvasses a range of practice strategies and interventions utilised by workers and services who engage with young people experiencing problematic AOD use whilst also exploring the many and varied challenges associated with this type of work.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

Pharmacokinetic studies of a Chinese triple herbal drug formula

Yin Chen Hao Tang preparation (YCHTP) is a classic traditional Chinese medicine formula, which is commonly used for clinical treatment of hepatological diseases. In this study, a rapid and validated high-performance liquid chromatography (HPLC) method was developed to simultaneously identify 6,7-dimethylesculetin and geniposide in rat plasma. This assay was performed on a Dikma Diamonsil RP(18) column (200 mmx4.6 mm, 5 mum) with acetonitrile-methanol-water (0.1% formic acid) as the mobile phase, showing acceptable linearity, intra- and inter-day precision and accuracy (R.S.D.=5%), and absolute recovery for two analytes (74%); the limits of quantitation were 0.4 and 1.12 mug/ml, and the limits of detection were 0.06 and 0.09 mug/ml for two analytes. The developed method was successfully applied to study the effect of formula compatibility on the pharmacokinetics of 6,7-dimethylesculetin and geniposide in YCHTP when orally administrating an effective human daily dose of YCHTP to rats. We surmise that formula compatibility can significantly influence the pharmacokinetics of YCHTP, and we have elucidated and validated the compatible administration of YCHTP.

Vehicle-to-vehicle real-time relative positioning using 5.9 GHz DSRC media

Vehicular accidents are one of the deadliest safety hazards and accordingly an immense concern of individuals and governments. Although, a wide range of active autonomous safety systems, such as advanced driving assistance and lane keeping support, are introduced to facilitate safer driving experience, these stand-alone systems have limited capabilities in providing safety. Therefore, cooperative vehicular systems were proposed to fulfill more safety requirements. Most cooperative vehicle-to-vehicle safety applications require relative positioning accuracy of decimeter level with an update rate of at least 10 Hz. These requirements cannot be met via direct navigation or differential positioning techniques. This paper studies a cooperative vehicle platform that aims to facilitate real-time relative positioning (RRP) among adjacent vehicles. The developed system is capable of exchanging both GPS position solutions and raw observations using RTCM-104 format over vehicular dedicated short range communication (DSRC) links. Real-time kinematic (RTK) positioning technique is integrated into the system to enable RRP to be served as an embedded real-time warning system. The 5.9 GHz DSRC technology is adopted as the communication channel among road-side units (RSUs) and on-board units (OBUs) to distribute GPS corrections data received from a nearby reference station via the Internet using cellular technologies, by means of RSUs, as well as to exchange the vehicular real-time GPS raw observation data. Ultimately, each receiving vehicle calculates relative positions of its neighbors to attain a RRP map. A series of real-world data collection experiments was conducted to explore the synergies of both DSRC and positioning systems. The results demonstrate a significant enhancement in precision and availability of relative positioning at mobile vehicles.

Biomechanical aspects of seating comfort in vehicle seating package engineering

In this paper, problems are described which are related to the ergonomic assessment of vehicle package design in vehicle systems engineering. The traditional approach, using questionnaire techniques for a subjective assessment of comfort related to package design, is compared to a biomechanical approach. An example is given for ingress design. The biomechanical approach is based upon objective postural data. The experimental setup for the study is described and methods used for the biomechanical analysis are explained. Because the biomechanic assessment requires not only a complex experimental setup but also time consuming data processing, a systematic reduction and preparation of biomechanic data for classification with an Artificial Neural Network significantly improves the economy of the biomechanical method.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

The impact of interface modality on police officers' visual behaviour when using an in-vehicle system

Background Standard operating procedures state that police officers should not drive while interacting with their mobile data terminal (MDT) which provides in-vehicle information essential to police work. Such interactions do however occur in practice and represent a potential source of driver distraction. The MDT comprises visual output with manual input via touch screen and keyboard. This study investigated the potential for alternative input and output methods to mitigate driver distraction with specific focus on eye movements. Method Nineteen experienced drivers of police vehicles (one female) from the NSW Police Force completed four simulated urban drives. Three drives included a concurrent secondary task: imitation licence plate search using an emulated MDT. Three different interface methods were examined: Visual-Manual, Visual-Voice, and Audio-Voice (“Visual” and “Audio” = output modality; “Manual” and “Voice” = input modality). During each drive, eye movements were recorded using FaceLAB™ (Seeing Machines Ltd, Canberra, ACT). Gaze direction and glances on the MDT were assessed. Results The Visual-Voice and Visual-Manual interfaces resulted in a significantly greater number of glances towards the MDT than Audio-Voice or Baseline. The Visual-Manual and Visual-Voice interfaces resulted in significantly more glances to the display than Audio-Voice or Baseline. For longer duration glances (>2s and 1-2s) the Visual-Manual interface resulted in significantly more fixations than Baseline or Audio-Voice. The short duration glances (<1s) were significantly greater for both Visual-Voice and Visual-Manual compared with Baseline and Audio-Voice. There were no significant differences between Baseline and Audio-Voice. Conclusion An Audio-Voice interface has the greatest potential to decrease visual distraction to police drivers. However, it is acknowledged that an audio output may have limitations for information presentation compared with visual output. The Visual-Voice interface offers an environment where the capacity to present information is sustained, whilst distraction to the driver is reduced (compared to Visual-Manual) by enabling adaptation of fixation behaviour.

Impacts of vehicle-to-grid (V2G) technologies on electricity market operations

The Vehicle-to-Grid (V2G) concept is based on the newly developed and marketed technologies of hybrid petrol-electric vehicles, most notably represented by the Toyota Prius, in combination with significant structural changes to the world's energy economy, and the growing strain on electricity networks. The work described in this presentation focuses on the market and economic impacts of grid connected vehicles. We investigate price reduction effects and transmission system expansion cost reduction. We modelled a large numbers of plug-in-hybrid vehicle batteries by aggregating them into a virtual pumped-storage power station at the Australian national electricity market's (NEM) region level. The virtual power station concept models a centralised control for dispatching (operating) the aggregated electricity supply/demand capabilities of a large number of vehicles and their batteries. The actual level of output could be controlled by human or automated agents to either charge or discharge from/into the power grid. As previously mentioned the impacts of widespread deployments of this technology are likely to be economic, environmental and physical.

Vehicle energy throughput analysis as a drivetrain motor design aid

There are many variables to consider in the design of an electric motor. However, meeting the performance requirements for an electric vehicle drive may cause a designer to loose focus on its typical operation and hence fail to optimise the motor in the region where it processes the most power. This paper investigates operating requirements of electric vehicle motor drives using the University concept vehicle as an example. The paper outlines a methodology for determining primary operating region of a vehicle drive. The methodology is applied to standard driving cycles that are commonly used in the design and testing of vehicles.

Ironless wheel motor for a direct drive vehicle application

An ironless motor for use as direct wheel drive is presented. The motor is intended for use in a lightweight (600kg), low drag, series hybrid commuter vehicle under development at The University of Queensland. The vehicle will utilise these ironless motors in each of its rear wheels, with each motor producing a peak torque output of 500Nm and a maximum rotational speed of 1500rpm. The axial flux motor consists of twin Ironless litz wire stators with a central magnetic ring and simplified Halbach magnet arrays on either side. A small amount of iron is used to support the outer Halbach arrays and to improve the peak magnetic flux density. Ducted air cooling is used to remove heat from the motor and will allow for a continuous torque rating of 250Nm. Ironless machines have previously been shown to be effective in high speed, high frequency applications (+1000Hz). They are generally regarded as non-optimal for low speed applications as iron cores allow for better magnet utilisation and do not significantly increase the weight of a machine. However, ironless machines can also be seen to be effective in applications where the average torque requirement is much lower than the peak torque requirement such as in some vehicle drive applications. The low spinning losses in ironless machines are shown to result in very high energy throughput efficiency in a wide range of vehicle driving cycles.

Brake system performance requirements of a lightweight electric/hybrid rear wheel drive vehicle

Investigates the braking performance requirements of the UltraCommuter, a lightweight series hybrid electric vehicle currently under development at the University of Queensland. With a predicted vehicle mass of 600 kg and two in-wheel motors each capable of 500 Nm of peak torque, decelerations up to 0.46 g are theoretically possible using purely regenerative braking. With 99% of braking demands less than 0.35 g, essentially all braking can be regenerative. The wheel motors have sufficient peak torque capability to lock the rear wheels in combination with front axle braking, eliminating the need for friction braking at the rear. Emergency braking levels approaching 1 g are achieved by supplementation with front disk brakes. This paper presents equations describing the peak front and rear axle braking forces which occur under straight line braking, including gradients. Conventionally, to guarantee stability, mechanical front/rear proportioning of braking effort ensures that the front axle locks first. In this application, all braking is initially regenerative at the rear, and an adaptive ''by-wire'' proportioning system presented ensures this stability requirement is still satisfied. Front wheel drive and all wheel drive systems are also discussed. Finally, peak and continuous performance measures, not commonly provided for friction brakes, are derived for the UltraCommuter's motor capability and range of operation.

The UltraCommuter : a viable and desirable solar-powered commuter vehicle

The University of Queensland UltraCommuter project is the demonstration of an ultra-light weight, low drag, energy efficient and low polluting, electric commuter vehicle equipped with a 2.5m2 on-board solar array. A key goal of the project is to make the vehicle predominantly self-sufficient from solar power for normal driving purposes , so that it does not require charging or refuelling from off-board sources. This paper examines the technical feasibility of the solar-powered commuter vehicle concept, as it applies the UltraCommuter project. A parametric description of a solar-powered commuter vehicle is presented. Real solar insolation data is then used to predict the solar driving range for the UltraCommuter and this is compared to typical urban usage patterns for commuter vehicles in Queensland. A comparative analysis of annual greenhouse gas emissions from the vehicle is also presented. The results show that the UltraCommuter’s on-board solar array can provide substantial supplementation of the energy required for normal driving, powering 90% of annual travel needs for an average QLD passenger vehicle. The vehicle also has excellent potential to reduce annual greenhouse gas emissions from the private transport sector, achieving a 98% reduction in CO2 emissions when compared to the average QLD passenger vehicle. Lastly, the vehicle battery pack provides for tolerance to consecutive days of poor weather without resorting to grid charging, giving uninterrupted functionality to the user. These results hold great promise for the technical feasibility of the solar-powered commuter vehicle concept.