title: The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

authors: Gardyne, Stephen J.

subjects: melt extrusion

abstract: Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 μg h⁻¹ with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 μg h⁻¹. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556 μg cm⁻² h⁻⁰˙⁵ with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100 μg cm⁻²h⁻⁰˙⁵. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R²=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug diffusion through the PCL with release rate involving an additional dissolution process (of the drug) before permeation occurs accounting for the moderate correlation. In general, of the eight drugs considered, it was clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally not suited to drug delivery via PCL under the conditions used. However, ketoprofen was found to be very suitable as a drug candidate for melt extrusion with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing potential as candidates though to a much lesser extent.

text: The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 μg h⁻¹ with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 μg h⁻¹. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556 μg cm⁻² h⁻⁰˙⁵ with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100 μg cm⁻²h⁻⁰˙⁵. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R²=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug diffusion through the PCL with release rate involving an additional dissolution process (of the drug) before permeation occurs accounting for the moderate correlation. In general, of the eight drugs considered, it was clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally not suited to drug delivery via PCL under the conditions used. However, ketoprofen was found to be very suitable as a drug candidate for melt extrusion with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing potential as candidates though to a much lesser extent.

year: 2011-05

title: The critical role of technical and social principles and values in encryption regulation

authors: Dizon, Michael

abstract: Encryption is a complex and enigmatic technology that poses significant challenges to regulators. While encryption is crucial to preserving the security and privacy of information and communications, it can also be used for illegal purposes and means and impede criminal investigations. Governments around the world have been proposing various ways to regulate this technology since the widespread presence and use of computers and the internet in the 1990s. Legislators have unsurprisingly taken a very law-centred approach to regulating encryption. They assume that the enactment of laws can definitively solve the problems brought about by new or disruptive technologies such as encryption. This regulatory mindset is encapsulated in a statement made by former Austrian Prime Minister Turnbull about how law trumps the underlying mathematics of encryption. He said, “The laws of Australia prevail in Australia, I can assure you of that. The laws of mathematics are very commendable, but the only law that applies in Australia is the law of Australia”. The issue with this exceedingly narrow and one-sided view of the relationship between law and technology is that it neglects to take into account important non-legal factors and considerations that are necessary in order to properly deal with encryption or any technology for that matter. Focusing solely on the laws and legal aspects of encryption without sufficient recognition of its technical and social contexts and conditions can result in the adoption of laws that are either ineffectual or unacceptable to the relevant stakeholders or society as a whole. This presentation will discuss the attendant technical and social principles and values of encryption that must be considered when seeking to develop appropriate laws and policies. Through the examination of the often overlooked technical and social dimensions of encryption, this presentation can provide key insights into how to better regulate encryption and technology more generally.

text: The critical role of technical and social principles and values in encryption regulation Encryption is a complex and enigmatic technology that poses significant challenges to regulators. While encryption is crucial to preserving the security and privacy of information and communications, it can also be used for illegal purposes and means and impede criminal investigations. Governments around the world have been proposing various ways to regulate this technology since the widespread presence and use of computers and the internet in the 1990s. Legislators have unsurprisingly taken a very law-centred approach to regulating encryption. They assume that the enactment of laws can definitively solve the problems brought about by new or disruptive technologies such as encryption. This regulatory mindset is encapsulated in a statement made by former Austrian Prime Minister Turnbull about how law trumps the underlying mathematics of encryption. He said, “The laws of Australia prevail in Australia, I can assure you of that. The laws of mathematics are very commendable, but the only law that applies in Australia is the law of Australia”. The issue with this exceedingly narrow and one-sided view of the relationship between law and technology is that it neglects to take into account important non-legal factors and considerations that are necessary in order to properly deal with encryption or any technology for that matter. Focusing solely on the laws and legal aspects of encryption without sufficient recognition of its technical and social contexts and conditions can result in the adoption of laws that are either ineffectual or unacceptable to the relevant stakeholders or society as a whole. This presentation will discuss the attendant technical and social principles and values of encryption that must be considered when seeking to develop appropriate laws and policies. Through the examination of the often overlooked technical and social dimensions of encryption, this presentation can provide key insights into how to better regulate encryption and technology more generally.

year: 2021-07-21

title: Mana Wahine Geographies: Spiritual, Spatial and Embodied Understandings of Papatūānuku

authors: Simmonds, Naomi Beth

subjects: Mana wahine

abstract: This thesis is a theoretical and empirical exploration of Māori women's knowledges and understandings of Papatūānuku in contemporary Aotearoa. The primary focus of this research is on the complexities, connections, and contradictions of Māori women's embodied relationships with the spaces of Papatūānuku - spaces that are simultaneously material, discursive, symbolic, and spiritual. In doing so, I displace the boundaries between coloniser/colonised, self/other, rational/irrational and scientific/spiritual. I demonstrate that Māori women's colonised realities produce multiple, complex and hybrid understandings of Papatūānuku. 

This thesis has three main strands. The first is theoretical. I offer mana wahine (Māori feminist discourses) as another perspective for geography that engages with the complex intersections of colonisation, race and gender. A mana wahine geography framework is a useful lens through which to explore the complexities of Māori women's relationships to space and place. This framework contributes to, and draws together, feminist geographies and Māori and indigenous academic scholarship.

Autobiographical material is woven with joint and individual semi-structured in-depth interviews conducted with nine Māori women in the Waikato region. The second strand, woven into this thesis, is a critical examination of the colonisation of Māori women's spiritual and embodied relationships to Papatūānuku. The invisibility of Māori women's knowledges in dominant conceptualisations of mythology, tikanga and wairua discourses is not a harmless omission rather it contains a political imperative that maintains the hegemony of colonialism and patriarchy. I argue that to understand further Māori women's relationships to space and place an examination of wairua discourses is necessary.

The third strand reconfigures embodied and spatial conceptualisations of Papatūānuku. Māori women's maternal bodies are intimately tied to Papatūānuku in a way that challenges the oppositional distinctions between mind/body and biology/social inscription. Māori women's maternal bodies (and the representation of them in te reo Māori) are constructed by, and in turn, construct Papatūānuku. Furthermore, women's spatial relationship to tūrangawaewae, home space and wider environmental concerns demonstrates the co-constitution of subjectivities, bodies and space/place. 

My hope is that this thesis will add to geographical literature by addressing previously ignored knowledges and that it will contribute to indigenous scholarship by providing a spatial perspective.

text: Mana Wahine Geographies: Spiritual, Spatial and Embodied Understandings of Papatūānuku This thesis is a theoretical and empirical exploration of Māori women's knowledges and understandings of Papatūānuku in contemporary Aotearoa. The primary focus of this research is on the complexities, connections, and contradictions of Māori women's embodied relationships with the spaces of Papatūānuku - spaces that are simultaneously material, discursive, symbolic, and spiritual. In doing so, I displace the boundaries between coloniser/colonised, self/other, rational/irrational and scientific/spiritual. I demonstrate that Māori women's colonised realities produce multiple, complex and hybrid understandings of Papatūānuku. 

This thesis has three main strands. The first is theoretical. I offer mana wahine (Māori feminist discourses) as another perspective for geography that engages with the complex intersections of colonisation, race and gender. A mana wahine geography framework is a useful lens through which to explore the complexities of Māori women's relationships to space and place. This framework contributes to, and draws together, feminist geographies and Māori and indigenous academic scholarship.

Autobiographical material is woven with joint and individual semi-structured in-depth interviews conducted with nine Māori women in the Waikato region. The second strand, woven into this thesis, is a critical examination of the colonisation of Māori women's spiritual and embodied relationships to Papatūānuku. The invisibility of Māori women's knowledges in dominant conceptualisations of mythology, tikanga and wairua discourses is not a harmless omission rather it contains a political imperative that maintains the hegemony of colonialism and patriarchy. I argue that to understand further Māori women's relationships to space and place an examination of wairua discourses is necessary.

The third strand reconfigures embodied and spatial conceptualisations of Papatūānuku. Māori women's maternal bodies are intimately tied to Papatūānuku in a way that challenges the oppositional distinctions between mind/body and biology/social inscription. Māori women's maternal bodies (and the representation of them in te reo Māori) are constructed by, and in turn, construct Papatūānuku. Furthermore, women's spatial relationship to tūrangawaewae, home space and wider environmental concerns demonstrates the co-constitution of subjectivities, bodies and space/place. 

My hope is that this thesis will add to geographical literature by addressing previously ignored knowledges and that it will contribute to indigenous scholarship by providing a spatial perspective.

year: 2009