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.

Comment on "Local accumulation times for source, diffusion, and degradation models in two and three dimensions" [J. Chem. Phys. 138, 104121 (2013)]

In a recent paper, Gordon, Muratov, and Shvartsman studied a partial differential equation (PDE) model describing radially symmetric diffusion and degradation in two and three dimensions. They paid particular attention to the local accumulation time (LAT), also known in the literature as the mean action time, which is a spatially dependent timescale that can be used to provide an estimate of the time required for the transient solution to effectively reach steady state. They presented exact results for three-dimensional applications and gave approximate results for the two-dimensional analogue. Here we make two generalizations of Gordon, Muratov, and Shvartsman’s work: (i) we present an exact expression for the LAT in any dimension and (ii) we present an exact expression for the variance of the distribution. The variance provides useful information regarding the spread about the mean that is not captured by the LAT. We conclude by describing further extensions of the model that were not considered by Gordon,Muratov, and Shvartsman. We have found that exact expressions for the LAT can also be derived for these important extensions...

The interplay between chondrocyte redifferentiation pellet size and oxygen concentration

Chondrocytes dedifferentiate during ex vivo expansion on 2-dimensional surfaces. Aggregation of the expanded cells into 3-dimensional pellets, in the presence of induction factors, facilitates their redifferentiation and restoration of the chondrogenic phenotype. Typically 1×105–5×105 chondrocytes are aggregated, resulting in “macro” pellets having diameters ranging from 1–2 mm. These macropellets are commonly used to study redifferentiation, and recently macropellets of autologous chondrocytes have been implanted directly into articular cartilage defects to facilitate their repair. However, diffusion of metabolites over the 1–2 mm pellet length-scales is inefficient, resulting in radial tissue heterogeneity. Herein we demonstrate that the aggregation of 2×105 human chondrocytes into micropellets of 166 cells each, rather than into larger single macropellets, enhances chondrogenic redifferentiation. In this study, we describe the development of a cost effective fabrication strategy to manufacture a microwell surface for the large-scale production of micropellets. The thousands of micropellets were manufactured using the microwell platform, which is an array of 360×360 µm microwells cast into polydimethylsiloxane (PDMS), that has been surface modified with an electrostatic multilayer of hyaluronic acid and chitosan to enhance micropellet formation. Such surface modification was essential to prevent chondrocyte spreading on the PDMS. Sulfated glycosaminoglycan (sGAG) production and collagen II gene expression in chondrocyte micropellets increased significantly relative to macropellet controls, and redifferentiation was enhanced in both macro and micropellets with the provision of a hypoxic atmosphere (2% O2). Once micropellet formation had been optimized, we demonstrated that micropellets could be assembled into larger cartilage tissues. Our results indicate that micropellet amalgamation efficiency is inversely related to the time cultured as discreet microtissues. In summary, we describe a micropellet production platform that represents an efficient tool for studying chondrocyte redifferentiation and demonstrate that the micropellets could be assembled into larger tissues, potentially useful in cartilage defect repair.

The role of the board of directors in ensuring a culture of integrity

Corporate scandals are as old as the corporate form itself. Consider, for example, the controversies surrounding the role of one of the first modern corporations, the British East India Company, in the Bengal famine of 1770 and in the Chinese opium trade. Yet it is the increasing scale and scope of unethical acts carried out by individuals in the name, and interests, of corporations that continue to be concerning. Recent revelations surrounding the extent of bribery and covert surveillance used by News Corporation journalists in its British operations continue to shock the world and undermine confidence in that organiszation and journalists in general. Yet despite the systemic nature of many of these unethical activities, corporate leaders generally plead ignorance when transgressions come to light. During the enquity into the News Corporation scandal, Rupert Murdoch, the CEO and chairman, rejected the assertion that he was ultimately 'responsible for this whole fiasco' (House of Commons, 2011, Q.230). Instead, like many corporate leaders before him, Murdoch placed blame on the employees within the newspaper. His responses poses an increasingly important question: Do corporate leaders bear responsibility for the conduct of individuals within a corporation and, if so, why?

Influence of drying conditions on the moisture diffusion during single stage and two stage fluidized bed drying of bovine intestine for pet food

Bovine intestine samples were heat pump fluidized bed dried at atmospheric pressure and at temperatures below and above the material freezing points equipped with a continuous monitoring system. The investigation of the drying characteristics has been conducted in the temperature range -10~25oC and the airflow in the range 1.5~2.5 m/s. Some experiments were conducted as a single temperature drying experiments and others as two stage drying experiments employing two temperatures. An Arrhenius-type equation was used to interpret the influence of the drying air parameters on the effective diffusivity, calculated with the method of slopes in terms of energy activation, and this was found to be sensitivity of the temperature. The effective diffusion coefficient of moisture transfer was determined by Fickian method using uni-dimensional moisture movement in both moisture, removal by evaporation and combined sublimation and evaporation. Correlations expressing the effective moisture diffusivity and drying temperature are reported.

Access to East European and Eurasian culture : publishing, acquisitions, digitization, metadata

Review of the book 'Access to East European and Eurasian culture: publishing, acquisitions, digitization, metadata', edited by Miranda Remnek, published by Haworth Information Press, 2009.

The Cyndi Lauper affect : bodies, girlhood and popular culture

Using a collective biography method informed by a Deleuzian theoretical approach (Davies and Gannon 2009, 2012), this article analyses embodied memories of girlhood becomings through affective engagements with resonating images in media and popular culture. In this approach to analysis we move beyond the impasse in some feminist cultural studies where studies of popular culture have been understood through theories of representation and reception that retain a sense of discrete subjectivity and linear effects. In these approaches, analysis focuses respectively on decoding and deciphering images in terms of their normative and ideological baggage, and, particularly with moving images, on psychological readings. Understanding bodies and popular culture through Deleuzian notions of “becoming” and “assemblage” opens possibilities for feminist researchers to consider the ways in which bodies are not separate from images but are, rather, becomings that are known, felt, materialized and mobilized with/through images(Coleman 2008a, 2008b, 2008c, 2009, 2011; Ringrose and Coleman 2013). We tease out the implications of this new approach to media affects through three memories of girls’ engagements with media images, reconceived as moments of embodied being within affective flows of popular culture that might momentarily extend upon ways of being and doing girlhood.

First-principle studies of the formation and diffusion of hydrogen vacancies in magnesium hydride

Ab initio density functional theory (DFT) calculations are performed to study the formation and diffusion of hydrogen vacancies on MgH2(110) surface and in bulk. We find that the formation energies for a single H-vacancy increase slightly from the surface to deep layers. The energies for creating adjacent surface divancacies at two inplane sites and at an inplane and a bridge site are even smaller than that for the formation of a single H-vacancy, a fact that is attributed to the strong vacancy−vacancy interactions. The diffusion of an H-vacancy from an in-plane site to a bridge site on the surface has the smallest activation barrier calculated at 0.15 eV and should be fast at room temperature. The activation barriers computed for H-vacancy diffusion from the surface into sublayers are all less than 0.70 eV, which is much smaller than the activation energy for desorption of hydrogen on the MgH2(110) surface (1.78−2.80 eV/H2). This suggests that surface desorption is more likely than vacancy diffusion to be rate determining, such that finding effective catalyst on the MgH2 surface to facilitate desorption will be very important for improving overall dehydrogenation performance.

Atomic hydrogen diffusion in novel magnesium nanostructures : the impact of incorporated subsurface carbon atoms

Ab initio Density Functional Theory (DFT) calculations are performed to study the diffusion of atomic hydrogen on a Mg(0001) surface and their migration into the subsurface layers. A carbon atom located initially on a Mg(0001) surface can migrate into the sub-surface layer and occupy a fcc site, with charge transfer to the C atom from neighboring Mg atoms. The cluster of postively charged Mg atoms surrounding a sub-surface C is then shown to facilitate the dissociative chemisorption of molecular hydrogen on the Mg(0001) surface, and the surface migration and subsequent diffusion into the subsurface of atomic hydrogen. This helps rationalize the experimentally-observed improvement in absorption kinetics of H2 when graphite or single walled carbon nanotubes (SWCNT) are introduced into the Mg powder during ball milling.

Computer modeling of diffusion in biological tissues

Molecular-level computer simulations of restricted water diffusion can be used to develop models for relating diffusion tensor imaging measurements of anisotropic tissue to microstructural tissue characteristics. The diffusion tensors resulting from these simulations can then be analyzed in terms of their relationship to the structural anisotropy of the model used. As the translational motion of water molecules is essentially random, their dynamics can be effectively simulated using computers. In addition to modeling water dynamics and water-tissue interactions, the simulation software of the present study was developed to automatically generate collagen fiber networks from user-defined parameters. This flexibility provides the opportunity for further investigations of the relationship between the diffusion tensor of water and morphologically different models representing different anisotropic tissues.

A study of the diffusion characteristics of normal, delipidized and relipidized articular cartilage using magnetic resonance imaging

This paper assesses the capacity to provide semipermeability of the synthetic layer of surface-active phospholipids created to replace the depleted surface amorphous layer of articular cartilage. The surfaces of articular cartilage specimens in normal, delipidized, and relipidized conditions following incubation in dipalmitoyl-phosphatidylcholine and palmitoyl-oleoyl-phosphatidylcholine components of the joint lipid mixture were characterized nanoscopically with the atomic force microscope and also imaged as deuterium oxide (D2O) diffused transiently through these surfaces in a magnetic resonance imaging enclosure. The MR images were then used to determine the apparent diffusion coefficients in a purpose-built MATLAB®-based algorithm. Our results revealed that all surfaces were permeable to D2O, but that there was a significant difference in the semipermeability of the surfaces under the different conditions, relative to the apparent diffusion coefficients. Based on the results and observations, it can be concluded that the synthetic lipid that is deposited to replace the depleted SAL of articular cartilage is capable of inducing some level of semipermeability.

Newstead House : the social history, culture and architecture of a bygone era

Historic house museums form a significant component of the built heritage and social history of a country. They vary from the elaborate mansions of the wealthy to modest dwellings of the working class. Regardless of the original owner's status in society these house museums are vital to an understanding of architecture, culture and society from a bygone era. The Newstead House, the oldest surviving residence, in Brisbane, is the first house to be designated a 'Historic House Museum' in Queensland. It is a representative example of a house that demonstrates the British colonial heritage of 19th century Australia. Originally a modest cottage, on 34 acres of land, the Newstead house was built by a Scottish migrant. The ownership of the house and land changed many times, during the period from 1847 to 1939. During this period a series of prominent residents of Brisbane either owned or rented this residence. They included, an officer of the Royal Navy, politicians, magistrates, merchant ship owners, and a Consul General of the United States of America. As a result, the house went through a series of renovations and extensions to accommodate the needs of its owners and their position in society. This paper aims to investigate the significance of historic museum houses in educating the community on aspects of social history, culture and architecture of 19th century Australia. It will focus on the heritage listed Newstead House as a case study to demonstrate the significance of the house as an artefact and an educational tool.

Integration of Saudi Arabia’s conservative Islamic culture in sustainable housing design

The cities of Saudi Arabia have perhaps the largest growth rates of cities in the Middle East, such that it has become a cause in shortage of housing for mid and low-income families, as is the case in other developing countries. Even when housing is found, it is not sustainable nor is it providing the cultural needs of those families. The aim of this paper is to integrate the unique conservative Islamic Saudi culture into the design of sustainable housing. This paper is part of a preliminary study of an on-going PhD thesis, which utilises a semistructured interview of a panel of nine experts in collecting the data. The interviews consisted of ten questions ranging from general questions such as stating their expertise and work position to more specific question such as listing the critical success factors and/or barriers for applying sustainability to housing in Saudi Arabia. Since the participants were selected according to their experience, the answers to the interview questions were satisfactory where the generation of the survey questions for the second stage in the PhD thesis took place after analysing the participant’s answers to the interview questions. This paper recommends design requirements for accommodating the conservative Islamic Saudi Culture in low cost sustainable houses. Such requirements include achieving privacy through the use of various types of traditional Saudi architectural elements, such as the method of decorative screening of windows, called Mashrabiya, and having an inner courtyard where the house looks inward rather than outward. Other requirements include educating firms on how to design sustainable housing, educating the public on the advantages of sustainable housing and implementing new laws that enforce the utilisation of sustainable methods to housing construction. This paper contributes towards the body of knowledge by proposing initial findings on how to integrate the conservative Islamic culture of Saudi Arabia into the design of a sustainable house specifically for mid and low-income families. This contribution can be implemented on developing countries in the region that are faced with housing shortage for mid and low-income families.

The impact of organisational culture in project selection process : case of public infrastructure project in Indonesia

The thesis develops an Organisational Culture (OC) based framework for potentially improving the current practice of the infrastructure project selection process (PSP) in Indonesia, particularly for regional road projects. This framework is developed to address the suggestion emanating from the research that there is a need for strengthening the relevant organisational culture dimensions and making changes to current organisational culture profiles to support the effectiveness of the decision-making process of the current PSP. The findings not only benefit existing knowledge but also provide practical contributions for those decision-makers within the Indonesian regional government that are involved in PSP, i.e. by raising the awareness of the influence and the role of organisational culture.

Numerical simulation of anomalous diffusion with application to medical imaging

The first objective of this project is to develop new efficient numerical methods and supporting error and convergence analysis for solving fractional partial differential equations to study anomalous diffusion in biological tissue such as the human brain. The second objective is to develop a new efficient fractional differential-based approach for texture enhancement in image processing. The results of the thesis highlight that the fractional order analysis captured important features of nuclear magnetic resonance (NMR) relaxation and can be used to improve the quality of medical imaging.