Formulation of multiparticulate systems as lyophilised orally disintegrating tablets

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality.

Formulation and process engineering of freeze-dried orally disintegrating tablets

Orally disintegrating tablets (ODTs) which are also referred to as orodispersible and fast disintegrating tablets, are solid oral dosage forms which upon placing on the tongue, disperse/disintegrate rapidly before being swallowed as a suspension or solution. ODTs are therefore easier and more convenient to administer than conventional tablets and are particularly beneficial for paediatric and geriatric patients, who generally have difficulty swallowing their medication. The work presented in this thesis involved the formulation and process development of ODTs, prepared using freeze-drying. Gelatin is one of the principal excipients used in the formulation of freeze-dried ODTs. One of the studies presented in this thesis investigated the potential modification of the properties of this excipient, in order to improve the performance of the tablets. As gelatin is derived from animal sources, a number of ethical issues surround its use as an excipient in pharmaceutical preparations. This was one of the motivations, Methocel™ and Kollicoat® IR were evaluated as binders as alternative materials to gelatin. Polyox™ was also evaluated as a binder together with its potential uses as a viscosity increasing and mucoadhesive agent to increase the retention of tablets in the mouth to encourage pre-gastric absorption of active pharmaceutical ingredients (APIs). The in vitro oral retention of freeze-dried ODT formulations was one property which was assessed in a design of experiments – factorial design study, which was carried out to further understand the role that formulation excipients have on the properties of the tablets. Finally, the novel approach of incorporating polymeric nanoparticles in freeze-dried ODTs was investigated, to study if the release profile of APIs could be modified, which could improve their therapeutic effect. The results from these studies demonstrated that the properties of gelatin-based formulations can be modified by adjusting pH and ionic strength. Adjustment of formulation pH has shown to significantly reduce tablet disintegration time. Evaluating Methocel™, in particular low viscosity grades, and Kollicoat® IR as binders has shown that these polymers can form tablets of satisfactory hardness and disintegration time. Investigating Polyox™ as an excipient in freeze-dried ODT formulations revealed that low viscosity grades appear suitable as binders whilst higher viscosity grades could potentially be utilised as viscosity increasing and mucoadhesive agents. The design of experiments – factorial design study revealed the influence of individual excipients in a formulation mix on resultant tablet properties and in vitro oral retention of APIs. Novel methods have been developed, which allows the incorporation of polymeric nanoparticles in situ in freeze-dried ODT formulations, which allows the modification of the release profile of APIs.

Student success : the identification and support of first year university students at risk of attrition

The engagement behaviour of 1,524 student-enrolments (“students”) in five first year units was monitored and 608 (39.9%) were classified as “at risk” using the criterion of not submitting or failing their first assignment. Of these, 327 (53.8%) were successfully contacted (i.e., spoken to by phone) and provided with advice and/or referral to learning and personal support services while the remaining 281 (46.2%) could not be contacted. Nine hundred and sixteen students (60.1%) were classified as “not at risk.” Overall, the at risk group who were contacted achieved significantly higher end-of-semester final grades than, and persisted (completed the unit) at more than twice the rate of, the at risk group who were not contacted. There were variations among the units which were explained by the timing of the first assignment, specific teaching-learning processes and the structure of the curriculum. Implications for curriculum design and supporting first year students within a personal, social and academic framework are discussed.

Sustainability and mandatory disclosure in Queensland : an assessment of the impact on home buyer patterns

Sustainability Declarations were introduced by the Queensland State Government on 1 January 2010 as a compulsory measure for all dwelling sales. The purpose of this policy decision was to improve the relevance of sustainability in the home ownership decision making process. This paper assesses the initial impact of this initiative over its first year in operation. In partnership with the Real Estate Institute of Queensland, real estate agents and salespeople in Queensland were surveyed to determine what impact the Sustainability Declaration has had on home buyer decision making. The level of compliance by the real estate industry was also reviewed. These preliminary findings indicate a high level of compliance from the real estate industry, however results confirm that sustainability is yet to become a criterion of relevance to the majority of home buyers in Queensland. The Sustainability Declarations are a first step in raising awareness in home owners of the importance of sustainability in housing. Further monitoring of this impact will be carried out over time.

Home sustainability policy and mandatory disclosure. a survey of buyer and seller participation and awareness in Qld

Sustainability Declarations were introduced by the Queensland State Government on 1 January 2010 as a mandatory disclosure measure for all dwelling sales in the State. The purpose of this paper is to assess the impact this policy decision has had in the homebuyer decision-making process in the first year since its introduction and to consider the effectiveness of the legislation in meeting its policy objectives. This quantitative research comprised a two-part process: the first stage surveyed the level of compliance by the real estate industry with the legislative requirements. Stage two comprised an online survey of Real Estate Institute of Queensland members to determine what impact the Sustainability Declaration has had on home buyer decision making and how effective the legislative mechanisms have been in achieving the policy objectives. This paper assesses the initial impact of this initiative over its first year in operation. These preliminary findings indicate a high level of compliance from the real estate industry, however results confirm that sustainability is yet to become a criterion of relevance to the majority of homebuyers in Queensland. These quantitative findings support anecdotal evidence that the objectives of the legislation to increase homebuyer awareness and relevance of sustainability issues in the home are not being achieved. Sustainability Declarations are a first step in raising homebuyer awareness of the importance of sustainability in housing. Further monitoring of this impact will be carried out over time. This is the first research undertaken to assess the impact of this new mandatory disclosure legislation in Queensland, Australia. The findings will inform policy makers and assist them to assess the effectiveness of the current legislation in achieving its policy objectives.

Towards a model of spray-canopy interactions : interception, shatter, bounce and retention of droplets on horizontal leaves

Pesticides used in agricultural systems must be applied in economically viable and environmentally sensitive ways, and this often requires expensive field trials on spray deposition and retention by plant foliage. Computational models to describe whether a spray droplet sticks (adheres), bounces or shatters on impact, and if any rebounding parent or shatter daughter droplets are recaptured, would provide an estimate of spray retention and thereby act as a useful guide prior to any field trials. Parameter-driven interactive software has been implemented to enable the end-user to study and visualise droplet interception and impaction on a single, horizontal leaf. Living chenopodium, wheat and cotton leaves have been scanned to capture the surface topography and realistic virtual leaf surface models have been generated. Individual leaf models have then been subjected to virtual spray droplets and predictions made of droplet interception with the virtual plant leaf. Thereafter, the impaction behaviour of the droplets and the subsequent behaviour of any daughter droplets, up until re-capture, are simulated to give the predicted total spray retention by the leaf. A series of critical thresholds for the stick, bounce, and shatter elements in the impaction process have been developed for different combinations of formulation, droplet size and velocity, and leaf surface characteristics to provide this output. The results show that droplet properties, spray formulations and leaf surface characteristics all influence the predicted amount of spray retained on a horizontal leaf surface. Overall the predicted spray retention increases as formulation surface tension, static contact angle, droplet size and velocity decreases. Predicted retention on cotton is much higher than on chenopodium. The average predicted retention on a single horizontal leaf across all droplet size, velocity and formulations scenarios tested, is 18, 30 and 85% for chenopodium, wheat and cotton, respectively.

Speaker attribution of Australian broadcast news data

Speaker attribution is the task of annotating a spoken audio archive based on speaker identities. This can be achieved using speaker diarization and speaker linking. In our previous work, we proposed an efficient attribution system, using complete-linkage clustering, for conducting attribution of large sets of two-speaker telephone data. In this paper, we build on our proposed approach to achieve a robust system, applicable to multiple recording domains. To do this, we first extend the diarization module of our system to accommodate multi-speaker (>2) recordings. We achieve this through using a robust cross-likelihood ratio (CLR) threshold stopping criterion for clustering, as opposed to the original stopping criterion of two speakers used for telephone data. We evaluate this baseline diarization module across a dataset of Australian broadcast news recordings, showing a significant lack of diarization accuracy without previous knowledge of the true number of speakers within a recording. We thus propose applying an additional pass of complete-linkage clustering to the diarization module, demonstrating an absolute improvement of 20% in diarization error rate (DER). We then evaluate our proposed multi-domain attribution system across the broadcast news data, demonstrating achievable attribution error rates (AER) as low as 17%.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Do the kinematics of a baulked take-off in springboard diving differ from those of a completed dive

Consistency and invariance in movements are traditionally viewed as essential features of skill acquisition and elite sports performance. This emphasis on the stabilization of action has resulted in important processes of adaptation in movement coordination during performance being overlooked in investigations of elite sport performance. Here we investigate whether differences exist between the movement kinematics displayed by five, elite springboard divers (age 17 ± 2.4 years) in the preparation phases of baulked and completed take-offs. The two-dimensional kinematic characteristics of the reverse somersault take-off phases (approach and hurdle) were recorded during normal training sessions and used for intra-individual analysis. All participants displayed observable differences in movement patterns at key events during the approach phase; however, the presence of similar global topological characteristics suggested that, overall, participants did not perform distinctly different movement patterns during completed and baulked dives. These findings provide a powerful rationale for coaches to consider assessing functional variability or adaptability of motor behaviour as a key criterion of successful performance in sports such as diving.

Test-retest reliability of physical activity measures used in Australian population surveys

PURPOSE Accurate monitoring of prevalence and trends in population levels of physical activity is fundamental to the planning of health promotion and disease-prevention strategies. Test-retest reliability (repeatability) was assessed for four self-report measures of physical activity commonly used in population surveys: the Active Australia survey (AA, N=356), the short form of the International Physical Activity Questionnaire (IPAQ-S, N=104), the physical activity items in the Behavioral Risk Factor Surveillance System (BRFSS, N=127) and the physical activity items in the Australian National Health Survey (NHS, N=122). METHODS Percent agreement and Kappa statistics were used to assess the reliability of classification of activity status (where ‘active’= 150 minutes of activity per week) and sedentariness (where ‘sedentary’ = reporting no physical activity). Intraclass correlations (ICCs) were used to assess agreement on minutes of activity reported for each item of each survey and on total minutes reported in each survey. RESULTS Percent agreement scores for both activity status and sedentariness were very good on all four instruments. Overall the percent agreement between repeated surveys was between 73% (NHS) and 87% (IPAQ) for the criterion measure of achieving 150 minutes per week, and between 77% (NHS) and 89% (IPAQ) for the criterion of being sedentary. Corresponding Kappa statistics ranged from 0.46 (NHS) to 0.61 (AA) for activity status and from 0.20 (BRFSS) to 0.52 (AA) for sedentariness. For the individual items ICCs were highest for walking (0.45 to 0.56) and vigorous activity (0.22 to 0.64) and lowest for the moderate questions (0.16 to 0.44). CONCLUSION All four measures provide acceptable levels of test-retest reliability for assessing both activity status and sedentariness, and moderate reliability for assessing total minutes of activity. Supported by the Australian Commonwealth Department of Health and Ageing.

Neuropsychological studies of late onset and subthreshold diagnoses of adult Attention-Deficit/Hyperactivity Disorder

Background Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. Methods We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. Results Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. Conclusions Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder.

Thermal Overstability Of Hydromagnetic Surface-Waves

We investigate the effects of radiative heat losses and thermal conductivity on the hydromagnetic surface waves along a magnetic discontinuity in a plasma of infinite electrical conductivity. We show that the effects of radiative heat losses on such surface waves are appreciable only when values of the plasma pressure on the two sides of the discontinuity are substantially different. Overstability of a surface wave requires that the medium in which it gives larger first-order compression should satisfy the criterion of Field (1965). Possible applications of the study to magnetic discontinuities in solar corona are briefly discussed.

Impact of resistance on the efficacy of binary combinations of spinosad, chlorpyrifos-methyl and s-methoprene against five stored-grain beetles

Laboratory experiments were conducted to determine the efficacy of spinosad (a biopesticide), chlorpyrifos-methyl (an organophosphorus compound (OP)) and s-methoprene (a juvenile hormone analogue) applied alone and in binary combinations against five stored-grain beetles in wheat. There were three strains of Rhyzopertha dominica, and one strain each of Sitophilus oryzae, Tribolium castaneum, Oryzaephilus surinamensis and Cryptolestes ferrugineus. These strains were chosen to represent a range of possible resistant genotypes, exhibiting resistance to organophosphates, pyrethroids or methoprene. Treatments were applied at rates that are registered or likely to be registered in Australia. Adults were exposed to freshly treated wheat for 2 weeks, and the effects of treatments on mortality and reproduction were determined. No single protectant or protectant combination controlled all insect strains, based on the criterion of >99% reduction in the number of live F1 adults relative to the control. The most effective combinations were spinosad at 1 mg kg-1+chlorpyrifos-methyl at 10 mg kg-1 which controlled all strains except for OP-resistant O. surinamensis, and chlorpyrifos-methyl at 10 mg kg-1+s-methoprene at 0.6 mg kg-1 which controlled all strains except for methoprene-resistant R. dominica. The results of this study demonstrate the difficulty in Australia, and potentially other countries which use protectants, of finding protectant treatments to control a broad range of pest species in the face of resistance development.

Evaluating the efficacy of the EZ-Ject herbicide system in Queensland, Australia

The EZ-Ject herbicide system was evaluated as a stem injection method for controlling woody weeds in a range of situations where traditional chemical application methods have limited scope. The equipment was trialled on three Queensland weed species; pond apple (Annona glabra), velvety tree pear (Opuntia tomentosa) and yellow oleander (Cascabela thevetia); at five different cartridge densities (0, 1, 2, 3 and 4) and with two herbicides (glyphosate and imazapyr). Cartridges filled with imazapyr were significantly more effective at controlling the three woody weed species than those filled with glyphosate. Injecting plants with three imazapyr cartridges resulted in plant kills ranging from 93 to 100%, compared with glyphosate kills of 17 to 100%. Pond apple was the most susceptible species, requiring one imazapyr cartridge or two glyphosate cartridges to kill 97 and 92% of the treated plants. Plant mortality increased as the number of cartridges injected increased. Mortality did not differ significantly for treatments receiving three and four imazapyr cartridges, as these cartridge densities met the criterion of injecting one cartridge per 10-cm basal circumference, a criterion recommended by the manufacturers for treating large plants (>6.35 cm in diameter at breast height). The cost of treating a weed infestation of 1500 plants ha–1 with three cartridges per tree is $1070 ha–1, with labour costs accounting for 16% of the total. The high chemical costs would preclude this technique from broad-scale use, but the method could have application for treating woody weeds in sensitive, high conservation areas.

Significance of Branching Angles in Streamer Discharges

The phenomenon of branching at specific angles in streamer breakdown studies is found to be more universal than was ever thought. The angles measured in the breakdown of gases show that the coefficient of field distortion, K, lies in the range from 1 to less than 0.1. The values of K, so obtained agree well with those envisaged in the criterion of the streamer mechanism. It is hoped that branching angles observed in various types of breakdown may, possibly, be explained similarly.