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: Towards a climate event stratigraphy for New Zealand over the past 30,000 years (NZ-INTIMATE project)

authors: Alloway, Brent V.

subjects: Last glacial coldest period

abstract: It is widely recognised that the acquisition of high-resolution palaeoclimate records from southern mid-latitude sites is essential for establishing a coherent picture of inter-hemispheric climate change and for better understanding of the role of Antarctic climate dynamics in the global climate system. New Zealand is considered to be a sensitive monitor of climate change because it is one of a few sizeable landmasses in the Southern Hemisphere westerly circulation zone, a critical transition zone between subtropical and Antarctic influences. New Zealand has mountainous axial ranges that amplify the climate signals and, consequently, the environmental gradients are highly sensitive to subtle changes in atmospheric and oceanic conditions. Since 1995, INTIMATE has, through a series of international workshops, sought ways to improve procedures for establishing the precise ages of climate events, and to correlate them with high precision, for the last 30 000 calendar years. The NZ-INTIMATE project commenced in late 2003, and has involved virtually the entire New Zealand palaeoclimate community. Its aim is to develop an event stratigraphy for the New Zealand region over the past 30 000 years, and to reconcile these events against the established climatostratigraphy of the last glacial cycle which has largely been developed from Northern Hemisphere records (e.g. Last Glacial Maximum (LGM), Termination I, Younger Dryas). An initial outcome of NZ-INTIMATE has been the identification of a series of well-dated, high-resolution onshore and offshore proxy records from a variety of latitudes and elevations on a common calendar timescale from 30 000 cal. yr BP to the present day. High-resolution records for the last glacial coldest period (LGCP) (including the LGM sensu stricto) and last glacial-interglacial transition (LGIT) from Auckland maars, Kaipo and Otamangakau wetlands on eastern and central North Island, marine core MD97-2121 east of southern North Island, speleothems on northwest South Island, Okarito wetland on southwestern South Island, are presented. Discontinuous (fragmentary) records comprising compilations of glacial sequences, fluvial sequences, loess accumulation, and aeolian quartz accumulation in an andesitic terrain are described. Comparisons with ice-core records from Antarctica (EPICA Dome C) and Greenland (GISP2) are discussed. A major advantage immediately evident from these records apart from the speleothem record, is that they are linked precisely by one or more tephra layers. Based on these New Zealand terrestrial and marine records, a reasonably coherent, regionally applicable, sequence of climatically linked stratigraphic events over the past 30 000 cal. yr is emerging. Three major climate events are recognised: (1) LGCP beginning at ca. 28 000 cal. yr BP, ending at Termination I, ca. 18 000 cal. yr BP, and including a warmer and more variable phase between ca. 27 000 and 21 000 cal. yr BP, (2) LGIT between ca. 18 000 and 11 600 cal. yr BP, including a Lateglacial warm period from ca. 14 800 to 13 500 cal. yr BP and a Lateglacial climate reversal between ca. 13 500 and 11 600 cal. yr BP, and (3) Holocene interglacial conditions, with two phases of greatest warmth between ca. 11 600 and 10 800 cal. yr BP and from ca. 6 800 to 6 500 cal. yr BP. Some key boundaries coincide with volcanic tephras.

text: Towards a climate event stratigraphy for New Zealand over the past 30,000 years (NZ-INTIMATE project) It is widely recognised that the acquisition of high-resolution palaeoclimate records from southern mid-latitude sites is essential for establishing a coherent picture of inter-hemispheric climate change and for better understanding of the role of Antarctic climate dynamics in the global climate system. New Zealand is considered to be a sensitive monitor of climate change because it is one of a few sizeable landmasses in the Southern Hemisphere westerly circulation zone, a critical transition zone between subtropical and Antarctic influences. New Zealand has mountainous axial ranges that amplify the climate signals and, consequently, the environmental gradients are highly sensitive to subtle changes in atmospheric and oceanic conditions. Since 1995, INTIMATE has, through a series of international workshops, sought ways to improve procedures for establishing the precise ages of climate events, and to correlate them with high precision, for the last 30 000 calendar years. The NZ-INTIMATE project commenced in late 2003, and has involved virtually the entire New Zealand palaeoclimate community. Its aim is to develop an event stratigraphy for the New Zealand region over the past 30 000 years, and to reconcile these events against the established climatostratigraphy of the last glacial cycle which has largely been developed from Northern Hemisphere records (e.g. Last Glacial Maximum (LGM), Termination I, Younger Dryas). An initial outcome of NZ-INTIMATE has been the identification of a series of well-dated, high-resolution onshore and offshore proxy records from a variety of latitudes and elevations on a common calendar timescale from 30 000 cal. yr BP to the present day. High-resolution records for the last glacial coldest period (LGCP) (including the LGM sensu stricto) and last glacial-interglacial transition (LGIT) from Auckland maars, Kaipo and Otamangakau wetlands on eastern and central North Island, marine core MD97-2121 east of southern North Island, speleothems on northwest South Island, Okarito wetland on southwestern South Island, are presented. Discontinuous (fragmentary) records comprising compilations of glacial sequences, fluvial sequences, loess accumulation, and aeolian quartz accumulation in an andesitic terrain are described. Comparisons with ice-core records from Antarctica (EPICA Dome C) and Greenland (GISP2) are discussed. A major advantage immediately evident from these records apart from the speleothem record, is that they are linked precisely by one or more tephra layers. Based on these New Zealand terrestrial and marine records, a reasonably coherent, regionally applicable, sequence of climatically linked stratigraphic events over the past 30 000 cal. yr is emerging. Three major climate events are recognised: (1) LGCP beginning at ca. 28 000 cal. yr BP, ending at Termination I, ca. 18 000 cal. yr BP, and including a warmer and more variable phase between ca. 27 000 and 21 000 cal. yr BP, (2) LGIT between ca. 18 000 and 11 600 cal. yr BP, including a Lateglacial warm period from ca. 14 800 to 13 500 cal. yr BP and a Lateglacial climate reversal between ca. 13 500 and 11 600 cal. yr BP, and (3) Holocene interglacial conditions, with two phases of greatest warmth between ca. 11 600 and 10 800 cal. yr BP and from ca. 6 800 to 6 500 cal. yr BP. Some key boundaries coincide with volcanic tephras.

year: 2007-01

title: Decolonisation as a social change framework and its impact on the development of Indigenous-based curricula for Helping Professionals in mainstream Tertiary Education Organisations

authors: Moeke-Pickering, Taima Materangatira

subjects: Indigenous Education

abstract: This research examined the social and political approaches that Indigenous peoples undertook to situate Indigenous-based education programmes in mainstream post-secondary/tertiary education organisations. Indigenous-based helping programmes assist to progress Indigenous aspirations for self-determination and are sites that center Indigenous worldviews. A decolonisation analysis framework that is embedded in the curriculum deepens students’ understanding about the impacts of imperialism, colonisation and post colonial issues. This thesis involved researching two Indigenous-based programmes that are based within mainstream tertiary institutes. The first is the Te Whiuwhiu o te Hau Maori Counselling degree programme which is based at the Waikato Institute of Technology (WINTEC) in Hamilton, Aotearoa, New Zealand. The other is the Native Human Services Social Work degree programme which is based at Laurentian University in Sudbury, Ontario, Canada. I start this thesis with “opening the circle” and situating the context for my research. Next is the literature review chapter. This chapter provides a review of decolonisation-colonisation, decolonisation frameworks within Indigenous education, self-determination and Indigenous peoples, and Maori and Native self-determination strategies relevant to health and education. I used a case study method combined with an Indigenous methodology to guide the research. This involved gathering key pieces of information as well as interviewing participants (graduates, tutors/faculty/developers) from each programme. In chapter four is the Te Whiuwhiu o te Hau case study and in chapter five is found the Native Human Services case study. Each case study covers pre-colonial and colonisation contexts and examines assimilative legislation on Indigenous education and health. The backgrounds of social work and counselling, Native social work and Maori counselling are also presented. In the case studies is the background and rationale for the development of each programme, as well as pertinent information on the course content. Chapter six presents on the findings and conclusion and chapter seven “closes the circle”. The main findings highlighted that Indigenous curricula and pedagogies embrace Indigenous theories and discourse relevant to the helping practice fields. Secondly, each programme fosters students to make positive changes for themselves, for their communities, and for their professions. Another finding is that faculty/tutors promote an inclusive Indigenous pedagogy in the classroom that incorporates cultural ceremonies, encourage personal introspection, builds cultural and professional skills, and teaches critical education. Both programmes reflected a pedagogy that taught students to counter negative narratives while instilling a critical analysis of decolonisation and colonisation. I propose that a decolonisation analysis is both a reflective and healing tool, in that students are provided with the hard evidence about their histories and what happened to their communities. I contend that Indigenous-based programmes contribute to the continuity of Indigenous culture and wellbeing of their communities and, that they play a vital role in advancing Indigenous education priorities.

text: Decolonisation as a social change framework and its impact on the development of Indigenous-based curricula for Helping Professionals in mainstream Tertiary Education Organisations This research examined the social and political approaches that Indigenous peoples undertook to situate Indigenous-based education programmes in mainstream post-secondary/tertiary education organisations. Indigenous-based helping programmes assist to progress Indigenous aspirations for self-determination and are sites that center Indigenous worldviews. A decolonisation analysis framework that is embedded in the curriculum deepens students’ understanding about the impacts of imperialism, colonisation and post colonial issues. This thesis involved researching two Indigenous-based programmes that are based within mainstream tertiary institutes. The first is the Te Whiuwhiu o te Hau Maori Counselling degree programme which is based at the Waikato Institute of Technology (WINTEC) in Hamilton, Aotearoa, New Zealand. The other is the Native Human Services Social Work degree programme which is based at Laurentian University in Sudbury, Ontario, Canada. I start this thesis with “opening the circle” and situating the context for my research. Next is the literature review chapter. This chapter provides a review of decolonisation-colonisation, decolonisation frameworks within Indigenous education, self-determination and Indigenous peoples, and Maori and Native self-determination strategies relevant to health and education. I used a case study method combined with an Indigenous methodology to guide the research. This involved gathering key pieces of information as well as interviewing participants (graduates, tutors/faculty/developers) from each programme. In chapter four is the Te Whiuwhiu o te Hau case study and in chapter five is found the Native Human Services case study. Each case study covers pre-colonial and colonisation contexts and examines assimilative legislation on Indigenous education and health. The backgrounds of social work and counselling, Native social work and Maori counselling are also presented. In the case studies is the background and rationale for the development of each programme, as well as pertinent information on the course content. Chapter six presents on the findings and conclusion and chapter seven “closes the circle”. The main findings highlighted that Indigenous curricula and pedagogies embrace Indigenous theories and discourse relevant to the helping practice fields. Secondly, each programme fosters students to make positive changes for themselves, for their communities, and for their professions. Another finding is that faculty/tutors promote an inclusive Indigenous pedagogy in the classroom that incorporates cultural ceremonies, encourage personal introspection, builds cultural and professional skills, and teaches critical education. Both programmes reflected a pedagogy that taught students to counter negative narratives while instilling a critical analysis of decolonisation and colonisation. I propose that a decolonisation analysis is both a reflective and healing tool, in that students are provided with the hard evidence about their histories and what happened to their communities. I contend that Indigenous-based programmes contribute to the continuity of Indigenous culture and wellbeing of their communities and, that they play a vital role in advancing Indigenous education priorities.

year: 2010