Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Modelling the flow of cane constituents in the milling process

A model has been developed to track the flow of cane constituents through the milling process. While previous models have tracked the flow of fibre, brix and water through the process, this model tracks the soluble and insoluble solid cane components using modelling theory and experiment data, assisting in further understanding the flow of constituents into mixed juice and final bagasse. The work provided an opportunity to understand the factors which affect the distribution of the cane constituents in juice and bagasse. Application of the model should lead to improvements in the overall performance of the milling train.

Diet, physical activity and substrate oxidation : implications for appetite control, weight loss and body composition

In many countries, governments and health agencies are strongly promoting physical activity as a means to prevent the accumulation of fatness that leads to weight gain and obesity. However, there is often a resistance to respond to health promotion initiatives. For example, in the UK, the Chief Medical Officer has recently reported that 71% of women and 61% of men fail to carry out even the minimal amount of physical activity recommended in the government’s guidelines. Similarly, the Food safety Agency has promoted reductions in the intake of fat, sugar and salt but with very little impact on the pattern of consumption. Why is it that recommendations to improve health are so difficult to implement, and produce the desired outcome?

Characterisation of sugarcane juice particles that influence the clarification process

Problems associated with processing whole sugarcane crop can be minimised by removing impurities during the clarification stage. As a first step, it is important to understand the colloidal chemistry of juice particles on a molecular level to assist development of strategies for effective clarification performance. This paper presents the composition and surface characteristics of colloidal particles originating from various juice types by using scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), X-ray photoelectron spectroscopy(XPS) and zeta potential measurements. The composition and surface characteristics of colloidal juice particles are reported. The results indicate that there are three types of colloidal particles present, viz. an aluminosilicatecompound, silica and iron oxide, with the latter two being abundant. Proteins, polysaccharides and organic acids were identified on the surface of particles in juice. The overall particle charge varies from -2 mV to -6 mV. In comparison to juice expressed from burnt cane, the zeta potential values were more negative with juice particles originating from whole crop. This in part explains why these juices are difficult to clarify.

Associations exist between food insecurity, poor diet, chronic illness and obesity among an Australian population

Food insecurity is the limited availability of, or access to, sufficient amounts of nutritious, culturally-appropriate and safe foods, or the inability to access such foods by socially-acceptable means. Evidence from the United States and Canada suggests that food insecurity may be associated with poor dietary intakes, obesity, and chronic disease including depression and diabetes, thus constituting a significant public health issue. Currently, no existing studies have investigated the dietary and health factors associated with food insecurity among the general Australian population. The current study investigated the potential associations between food insecurity, diet and health among Australian adults (18 years and over) participating in the cross-sectional National Health Survey (n = 19,500). Data were analysed by logistic regression adjusting for sociodemographic covariates. Those from food insecure households were 50% less likely to consume the recommended number of servings of fruit, 60% more likely to report poor health and experienced a 6-fold increase in the risk of severe depressive disorders, compared to their food secure counterparts. Furthermore, food insecurity was associated with a 50% increase in the risk of being diagnosed with ‘high sugar levels’. Finally, women from food insecure households were 30% more likely to be obese compared to their food secure counterparts. These findings suggest that food insecurity may play an important role in preventing adherence with national dietary recommendations, and may increase the risk of obesity and chronic illness. This has important implications for both clinical practice, and the development of interventions and policy to address food insecurity.

The effect of post-match alcohol ingestion on recovery from competitive Rugby League matches

This study investigated the effects of alcohol ingestion on lower body strength and power, and physiological and cognitive recovery following competitive Rugby League matches. Nine male Rugby players participated in two matches, followed by one of two randomized interventions; a control or alcohol ingestion session. Four hours post-match, participants consumed either beverages containing a total of 1g of ethanol per kg bodyweight (vodka and orange juice; ALC) or a caloric and taste matched non-alcoholic beverage (orange juice; CONT). Pre, post, 2 h post and 16 h post match measures of countermovement jump (CMJ), maximal voluntary contraction(MVC), voluntary activation (VA), damage and stress markers of creatine kinase (CK), C-reactive protein (CRP), cortisol, and testosterone analysed from venous blood collection, and cognitive function (modified Stroop test) were determined. Alcohol resulted in large effects for decreased CMJ height(-2.35 ± 8.14 and -10.53 ± 8.36 % decrement for CONT and ALC respectively; P=0.15, d=1.40), without changes in MVC (P=0.52, d=0.70) or VA (P=0.15, d=0.69). Furthermore, alcohol resulted in a significant slowing of total time in a cognitive test (P=0.04, d=1.59), whilst exhibiting large effects for detriments in congruent reaction time (P=0.19, d=1.73). Despite large effects for increased cortisol following alcohol ingestion during recovery (P=0.28, d=1.44), post-match alcohol consumption did not unduly affect testosterone (P-0.96, d=0.10), CK (P=0.66, d=0.70) or CRP(P=0.75, d=0.60). It appears alcohol consumption during the evening following competitive rugby matches may have some detrimental effects on peak power and cognitive recovery the morning following a Rugby League match. Accordingly, practitioners should be aware of the potential associated detrimental effects of alcohol consumption on recovery and provide alcohol awareness to athletes at post-match functions.

The potential for ethanol production from sugarcane in Australia

The Australian sugar industry processes approximately 35 million tonnes of sugarcane per year from 400 000 hectares of land. Sugar remains the principal revenue stream from sugarcane in Australia with less than 60 ML/y of fuel ethanol produced from final molasses at present. Modelling has been undertaken to estimate the potential ethanol production from the Australian sugar industry for integrated facilities producing both sugar and ethanol from the entire sugarcane resource. Although research aimed at developing commercial processes is ongoing, the use of a proportion of the bagasse and trash for ethanol production, in addition to juice and molasses fermentation, would allow significant increases in the scale of ethanol production from sugarcane in Australia, increasing total industry revenues while maintaining energy self sufficiency.

Towards a commercial lignocellulosic ethanol industry in Australia : the Mackay Renewable Biocommodities Pilot Plant

In 2007, the Queensland University of Technology (QUT) received funding from the Australian Government through the NCRIS program and from the then Queensland Government Department of State Development to construct a pilot research and development facility for the production of bioethanol and other renewable biocommodities from biomass including sugar cane bagasse. This facility is being constructed adjacent to the Racecourse Sugar Mill in Mackay and is known as the Mackay Renewable Biocommodities Pilot Plant (MRBPP). The MRBPP will be capable of processing biomass through a pressurised pretreatment reactor and includes equipment for enzymatic saccharification, fermentation and distillation to produce ethanol. Lignin and fermentation co-products will also be produced at a pilot scale for product development and testing.

An update on the Mackay Renewable Biocommodities Pilot Plant : preliminary trial results

THE Mackay Renewable Biocommodities Pilot Plant is a pilot scale facility owned and operated by QUT for research and demonstration of the conversion of lignocellulosic biomass such as sugarcane bagasse into biofuels. The pilot plant accommodates unique state-of-the-art equipment to process a wide range of feedstocks and is strategically located on the site of the Mackay Sugar Ltd Racecourse Mill. Major facilities include a biomass handling system, pre-treatment reactor, saccharification reactor, fermentors, distillation column and bioseparations equipment. This paper provides an update on the design, construction, commissioning and start-up of the facility. In addition, the paper provides results from preliminary facility trials on the pre-treatment of sugarcane bagasse for cellulosic ethanol production.

Predicting the effects of bagasse depithing operations on boiler combustion performance

The sugar industry is pursuing diversification options using bagasse as a feedstock. Depithing, the removal of the smaller bagasse particles, is an integral part of the manufacturing processes for bagasse by-products such as pulp and paper. There are possible environmental and economic benefits associated with incorporating depithing operations into a sugar factory. However there have only been limited investigations into the effects of depithing operations on a sugar factory boiler station. This paper describes a modelling investigation, using the lumped parameter boiler design tool BOILER and the CFD code FURNACE, to predict the effects of pith, depithed bagasse and mixed bagasse/pith firing on the efficiency, fuel consumption and combustion performance of a typical sugar factory boiler.

Modelling the flow of juice through a mill

A juice flow model has been developed to estimate the juice expression at the four nips of a sixroller mill. An extended volumetric theory was applied to determine the juice expressed at each nip. The model was applied to a first and final mill, using typical mill settings and an empirical equation to estimate reabsorption. Results of using the model for typical heavy-duty pressure feeder settings show that most of the juice is expressed at the pressure feeder nip. Since the pressure feeders are remote from the mill, a significant portion of the juice is expressed before the bagasse enters the mill.

Developing schedules for mixed rail and road cane transport systems

This paper addresses the problem of scheduling a cane transport system involving both rail transport and road transport, where the road transport operates from several sidings in the rail network. An iterative approach for scheduling the rail transport system has been developed using existing rail transport scheduling tools. The assumption that harvesters serviced by road transport are effectively operating from the rail siding from which their bins are supplied seems a reasonable starting point for the analysis. There is a need to manually modify the schedule to take into account the road transport schedule to ensure that full bins are not collected before the road transport system delivers them back to the rail siding.

Food policy, dietary intakes and chronic disease in prisons

International research on prisoners demonstrates poor health outcomes, including chronic disease, with the overall burden to the community high. Prisoners are predominantly male and young. In Australia, the average incarceration length is 3 years, sufficient to impact long term health, including nutrition. Food in prisons is highly controlled, yet gaps exist in policy. In most Western countries prisons promote healthy foods, often incongruent with prisoner expectations or wants. Few studies have been conducted on dietary intakes during incarceration in relation to food policy. In this study detailed diet histories were collected on 120/945 men (mean age = 32 years), in a high-secure prison. Intakes were verified via individual purchase records, mealtime observations, and audits of food preparation, purchasing and holdings. Physical measurements (including fasting bloods) were taken and medical records reviewed. Results showed the standard food provided consistent with current dietary guidelines, however limited in menu choice. Diet histories revealed self-funded foods contributing 1–63% of energy (mean = 30%), 0–83% sugar (mean = 38%), 1–77% saturated fats (mean = 31%) and 1–59% sodium (mean = 23%). High levels of modification to food provided was found using minimal cooking amenities and inclusion of self-funded foods and/or foods retained from previous meals. Medical records and physical measurements confirmed markers of chronic disease. This study highlights the need to establish clear guidelines on all food available in prisons if chronic disease risk reduction is a goal. This study has also supported evidenced based food and nutrition policy including menu choice, food quality, quantity and safety as well as type and access to self-funded foods.

Caustic potash pulping study of water efficient Arudno donax and Sorghum bicolor; a comparison to sugarcane bagasse

Numerous crops grow in sugar regions that have the potential to increase the amount of biomass available to a small bagasse-based pulp factory. Arundo donax and Sorghum offer unique advantages to farmers compared to other agricultural crops. Sorghum bicolour requires only 1/3 of the water of sugarcane. Arundo donax is a very high yield crop, it can also grow with little water but it has the further advantage in that it is also highly stress tolerant, making it suitable for land which is unsuited to other crops. Pulps produced from these crops were benchmarked against sugarcane bagasse pulp. Arundo, sorghum and bagasse were pulped using KOH and anthraquinone to 20 Kappa number so as to produce a bleachable pulp. The unbleached sorghum pulp has better tensile strength properties than the unbleached Arundo pulp (43.8 Nm/g compared to 21.4 Nm/g) and the bleached sorghum pulp tensile strength was similar to bagasse (28.4 Nm/g). At 20 Kappa number, sorghum pulp had acceptable yield for a non-wood fibre (45% c.f. 55% for bagasse), Arundo donax pulp had low tensile strength, and relatively low yield (38.7%), even for an agricultural fibre and required severe cooking conditions to achieve similar delignification to sugarcane bagasse or sorghum. Sorghum and Arundo donax produced thicker handsheets than bagasse (>160 μm c.f. 122 μm for bagasse). In preliminary experiments sorghum and bagasse responded slightly better to Totally Chlorine Free bleaching (QPP), although none achieved a satisfactory brightness level and more optimisation is needed.

Metabolic and ecological study of environmental pentose utilizing bacteria (E-PUB)

Lignocellulosic materials, such as sugar cane bagasse, a waste product of the sugarcane processing industry, agricultural residues and herbaceous crops, may serve as an abundant and comparatively cheap feedstock for largescale industrial fermentation, resulting in the production of marketable end-products. However, the complex structure of lignocellulosic materials, the presence of various hexose and pentose sugars in the hemicellulose component, and the presence of various compounds that inhibit the organisms selected for the fermentation process, all constitute barriers that add to the production costs and make full scale industrial production economically less feasible. The work presented in this thesis was conducted in order to screen microorganisms for ability to utilize pentose sugars derived from the sugar mill industrial waste. A large number of individual bacterial strains were investigated from hemi-cellulose rich material collected at the Proserpine and Maryborough sugar mills, notably soil samples from the mill sites. The research conducted to isolation of six pentose-capable Gram-positive organisms from the actinomycetes group by using pentose as a sole carbon source in the cultivation process. The isolates were identified as Corynebacterium glutamicum, Actinomyces odontolyticus, Nocardia elegans, and Propionibacterium freudenreichii all of which were isolated from the hemicellulose-enriched soil. Pentose degrading microbes are very rare in the environment, so this was a significant discovery. Previous research indicated that microbes could degrade pentose after genetic modification but the microbes discovered in this research were able to naturally utilize pentose. Six isolates, identified as four different genera, were investigated for their ability to utilize single sugars as substrates (glucose, xylose, arabinose or ribose), and also dual sugars as substrates (a hexose plus a pentose). The results demonstrated that C. glutamicum, A. odontolyticus, N. elegans, and P. freudenreichii were pentose-capable (able to grow using xylose or other pentose sugar), and also showed diauxie growth characteristics during the dual-sugar (glucose, in combination with xylose, arabinose or ribose) carbon source tests. In addition, it was shown that the isolates displayed very small differences in growth rates when grown on dual sugars as compared to single sugars, whether pentose or hexose in nature. The anabolic characteristics of C. glutamicum, A. odontolyticus, N. elegans and P. freudenreichii were subsequently investigated by qualitative analysis of their end-products, using high performance liquid chromatography (HPLC). All of the organisms produced arginine and cysteine after utilization of the pentose substrates alone. In addition, P. freudenreichii produced alanine and glycine. The end-product profile arising from culture with dual carbon sources was also tested. Interestingly, this time the product was different. All of them produced the amino acid glycine, when grown on a combination substrate-mix of glucose with xylose, and also glucose with arabinose. Only N. elegans was able to break down ribose, either singly or in combination with glucose, and the end-product of metabolism of the glucose plus ribose substrate combination was glutamic acid. The ecological analysis of microbial abundance in sugar mill waste was performed using denaturing gradient gel electrophoresis (DGGE) and also the metagenomic microarray PhyloChip method. Eleven solid samples and seven liquid samples were investigated. A very complex bacterial ecosystem was demonstrated in the seven liquid samples after testing with the PhyloChip method. It was also shown that bagasse leachate was the most different, compared to all of the other samples, by virtue of its richness in variety of taxa and the complexity of its bacterial community. The bacterial community in solid samples from Proserpine, Mackay and Maryborough sugar mills showed huge diversity. The information found from 16S rDNA sequencing results was that the bacterial genera Brevibacillus, Rhodospirillaceae, Bacillus, Vibrio and Pseudomonas were present in greatest abundance. In addition, Corynebacterium was also found in the soil samples. The metagenomic studies of the sugar mill samples demonstrate two important outcomes: firstly that the bagasse leachate, as potentially the most pentose-rich sample tested, had the most complex and diverse bacterial community; and secondly that the pentose-capable isolates that were initially discovered at the beginning of this study, were not amongst the most abundant taxonomic groups discovered in the sugar mill samples, and in fact were, as suspected, very rare. As a bioprospecting exercise, therefore, the study has discovered organisms that are naturally present, but in very small numbers, in the appropriate natural environment. This has implications for the industrial application of E-PUB, in that a seeding process using a starter culture will be necessary for industrial purposes, rather than simply assuming that natural fermentation might occur.