Dry powder inhaler formulations-effect of polymer carrier size on the drug dispersion

Background The size of the carrier influences the aerosolization of drug from a dry powder inhaler (DPI) formulation. Currently, lactose monohydrate particles in a variety of sizes are preferably used in carrier based DPI formulations of various drugs; however, contradictory reports exist regarding the effect of the size of the carrier on the dispersion of drug. In this study we examined the influence of the intrinsic particle size of the polymeric carrier on the aerosolization of a model drug salbutamol sulphate (SS). Methods Four different sizes (20–150 lm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS particles from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were by laser diffraction and SEM, respectively. Results The FPF from these carriers was found to be increasing from 5.6% to 21.3% with increasing the carrier size. The FPF was found to be greater (21%) with the highest particle size of the carrier (150 lm). Conclusions The aerosolization of drug was dependent on the size of polymer carriers. The smaller size of the carrier resulted in lower FPF which was increased with increasing the carrier size. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation

Purpose: This study investigated the effect of chemical conjugation of the amino acid L-leucine to the polysaccharide chitosan on the dispersibility and drug release pattern of a polymeric nanoparticle (NP)-based controlled release dry powder inhaler (DPI) formulation. Methods: A chemical conjugate of L-leucine with chitosan was synthesized and characterized by Infrared (IR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and X-ray Photoelectron Spectroscopy (XPS). Nanoparticles of both chitosan and its conjugate were prepared by a water-in-oil emulsification – glutaraldehyde cross-linking method using the antihypertensive agent, diltiazem (Dz) hydrochloride as the model drug. The surface morphology and particle size distribution of the nanoparticles were determined by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The dispersibility of the nanoparticle formulation was analysed by a Twin Stage Impinger (TSI) with a Rotahaler as the DPI device. Deposition of the particles in the different stages was determined by gravimetry and the amount of drug released was analysed by UV spectrophotometry. The release profile of the drug was studied in phosphate buffered saline at 37 ⁰C and analyzed by UV spectrophotometry. Results: The TSI study revealed that the fine particle fractions (FPF), as determined gravimetrically, for empty and drug-loaded conjugate nanoparticles were significantly higher than for the corresponding chitosan nanoparticles (24±1.2% and 21±0.7% vs 19±1.2% and 15±1.5% respectively; n=3, p<0.05). The FPF of drug-loaded chitosan and conjugate nanoparticles, in terms of the amount of drug determined spectrophotometrically, had similar values (21±0.7% vs 16±1.6%). After an initial burst, both chitosan and conjugate nanoparticles showed controlled release that lasted about 8 to 10 days, but conjugate nanoparticles showed twice as much total drug release compared to chitosan nanoparticles (~50% vs ~25%). Conjugate nanoparticles also showed significantly higher dug loading and entrapment efficiency than chitosan nanoparticles (conjugate: 20±1% & 46±1%, chitosan: 16±1% & 38±1%, n=3, p<0.05). Conclusion: Although L-leucine conjugation to chitosan increased dispersibility of formulated nanoparticles, the FPF values are still far from optimum. The particles showed a high level of initial burst release (chitosan, 16% and conjugate, 31%) that also will need further optimization.

Exploring schema-driven differences in situation awareness between road users : an on-road study of driver, cyclist and motorcyclist situation awareness

Collisions between different road users make a substantial contribution to road trauma. Although evidence suggests that different road users interpret the same road situations differently, it is not clear how road users' situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study conducted to examine driver, motorcyclist and cyclist situation awareness in different road environments. The findings suggest that, in addition to minor differences in the structure of different road users' situation awareness (i.e. amount of information and how it is integrated), the actual content of situation awareness in terms of road user schemata, the resulting interaction with the world and the information underpinning situation awareness is markedly different. Further examination indicates that the differences are likely to be compatible along arterial roads, shopping strips and at roundabouts, but that they may create conflicts between different road users at intersections. Interventions designed to support compatible situation awareness and behaviour between different road users are discussed. Practitioner Summary: Incompatible situation awareness plays a key role in collisions between different road users (e.g. drivers and motorcyclists). This on-road study examined situation awareness in drivers, motorcyclists and cyclists, identifying the key differences and potential conflicts that arise. The findings are used to propose interventions designed to enhance the compatibility of situation awareness between road users.

Road safety knowledge exchange and capacity building between China and Australia

Road traffic injuries are one of the major public health burdens worldwide. The United Nations Decade of Action for Road Safety (2011-2020) implores all nations to work to reduce this burden. This decade represents a unique and historic period of time in the field of road safety. Information exchange and co-operation between nations is an important step in achieving the goal. The burden of road crashes, fatalities and injuries is not equally distributed. We know that low and middle-income countries experience the majority of the road trauma burden. Therefore it is imperative that these countries learn from the successes of others that have developed and implemented road safety laws, public education campaigns and countermeasures over many years and have achieved significant road trauma reductions as a result. China is one of the countries experiencing a large road trauma burden. Vulnerable road users such as pedestrians and cyclists make up a large proportion of fatalities and injuries in China. Speeding, impaired/drug driving, distracted driving, vehicle overloading, inadequate road infrastructure, limited use of safety restraints and helmets, and limited road safety training have all been identified as contributing to the problem. Some important steps have been taken to strengthen China’s approach, including increased penalties for drunk driving in May 2011 and increased attention to school bus safety in 2011/12. However, there is still a large amount of work needed to improve the current road safety position in China. This paper provides details of a program to assist with road safety knowledge exchange between China and Australia that was funded by the Australian Government which was undertaken in the latter part of 2012. The four month program provided the opportunity for the first author to work closely with key agencies in Australia that are responsible for policy development and implementation of a broad range of road safety initiatives. In doing so, an in-depth understanding was gained about key road safety strategies in Australia and processes for developing and implementing them. Insights were also gained into the mechanisms used for road safety policy development, implementation and evaluation in several Australian jurisdictions. Road traffic law and enforcement issues were explored with the relevant jurisdictional transport and police agencies to provide a greater understanding of how Chinese laws and practices could be enhanced. Working with agencies responsible for public education and awareness campaigns about road safety in Australia also provided relevant information about how to promote road safety at the broader community level in China. Finally, the program provided opportunities to work closely with several world-renowned Australian research centres and key expert researchers to enhance opportunities for ongoing road safety research in China. The overall program provided the opportunity for the first author to develop knowledge in key areas of road safety strategy development, implementation and management which are directly relevant to the current situation in China. This paper describes some main observations and findings from participation in the program.

Slicing big data - Twitter, gambling and time sensitive information

Big Data presents many challenges related to volume, whether one is interested in studying past datasets or, even more problematically, attempting to work with live streams of data. The most obvious challenge, in a ‘noisy’ environment such as contemporary social media, is to collect the pertinent information; be that information for a specific study, tweets which can inform emergency services or other responders to an ongoing crisis, or give an advantage to those involved in prediction markets. Often, such a process is iterative, with keywords and hashtags changing with the passage of time, and both collection and analytic methodologies need to be continually adapted to respond to this changing information. While many of the data sets collected and analyzed are preformed, that is they are built around a particular keyword, hashtag, or set of authors, they still contain a large volume of information, much of which is unnecessary for the current purpose and/or potentially useful for future projects. Accordingly, this panel considers methods for separating and combining data to optimize big data research and report findings to stakeholders. The first paper considers possible coding mechanisms for incoming tweets during a crisis, taking a large stream of incoming tweets and selecting which of those need to be immediately placed in front of responders, for manual filtering and possible action. The paper suggests two solutions for this, content analysis and user profiling. In the former case, aspects of the tweet are assigned a score to assess its likely relationship to the topic at hand, and the urgency of the information, whilst the latter attempts to identify those users who are either serving as amplifiers of information or are known as an authoritative source. Through these techniques, the information contained in a large dataset could be filtered down to match the expected capacity of emergency responders, and knowledge as to the core keywords or hashtags relating to the current event is constantly refined for future data collection. The second paper is also concerned with identifying significant tweets, but in this case tweets relevant to particular prediction market; tennis betting. As increasing numbers of professional sports men and women create Twitter accounts to communicate with their fans, information is being shared regarding injuries, form and emotions which have the potential to impact on future results. As has already been demonstrated with leading US sports, such information is extremely valuable. Tennis, as with American Football (NFL) and Baseball (MLB) has paid subscription services which manually filter incoming news sources, including tweets, for information valuable to gamblers, gambling operators, and fantasy sports players. However, whilst such services are still niche operations, much of the value of information is lost by the time it reaches one of these services. The paper thus considers how information could be filtered from twitter user lists and hash tag or keyword monitoring, assessing the value of the source, information, and the prediction markets to which it may relate. The third paper examines methods for collecting Twitter data and following changes in an ongoing, dynamic social movement, such as the Occupy Wall Street movement. It involves the development of technical infrastructure to collect and make the tweets available for exploration and analysis. A strategy to respond to changes in the social movement is also required or the resulting tweets will only reflect the discussions and strategies the movement used at the time the keyword list is created — in a way, keyword creation is part strategy and part art. In this paper we describe strategies for the creation of a social media archive, specifically tweets related to the Occupy Wall Street movement, and methods for continuing to adapt data collection strategies as the movement’s presence in Twitter changes over time. We also discuss the opportunities and methods to extract data smaller slices of data from an archive of social media data to support a multitude of research projects in multiple fields of study. The common theme amongst these papers is that of constructing a data set, filtering it for a specific purpose, and then using the resulting information to aid in future data collection. The intention is that through the papers presented, and subsequent discussion, the panel will inform the wider research community not only on the objectives and limitations of data collection, live analytics, and filtering, but also on current and in-development methodologies that could be adopted by those working with such datasets, and how such approaches could be customized depending on the project stakeholders.

Campaigning for street trees, Sydney Botanic Gardens, 1890s to 1920s

Between the 1890s and 1920s street trees became a more prominent feature in streetscapes across New South Wales, Australia. The Sydney Botanic Gardens, with their extensive nursery system, were responsible for supplying seedlings to councils and municipalities for use as street trees. As such, this institution was a primary mover of what a street tree should be, how they should be used and what plants were best suited to this particular use in urban environments. This paper analyses the nurturing of this use of street trees by the Sydney Botanic Gardens and the Director Joseph Maiden. This institution was a place that moved not just stock and seedlings, but ideas about how nature's inclusion into urban environments had the capacity to influence and enhance the cultivation of civilised citizens. This was affected through access to transnational resources available to the Sydney Botanic Gardens.

'Haunts of the street bully' : social reform and the Queensland children's playground movement

This article is about the Queensland children's playground movement and its development in Brisbane. It pays particular attention to three Brisbane playgrounds: Neal Macrossan Playground (formerly Paddington Playground); Bedford Playground (formerly Spring Hill Playground); and the Valley Playground, which has since been replaced by a building. The paper pays especial attention to the work of the local children's playground protagonist Mary Josephine Bedford, which will be seen within the context of the international movement.

Failure to administer a drug and causation

Case note on King v Western Sydney Local Health Network In King v Western Sydney Local Health Network [2013] NSWCA 162 the appellant sought damages for the severe physical and intellectual disability she suffered as a result of foetal varicella syndrome (FVS) caused by her mother contracting varicella (chickenpox) in the second trimester of her pregnancy. The mother had been exposed to the virus and sought advice from a doctor at Blacktown Hospital as she had not had the virus herself and therefore did not possess immunity. In such circumstances at the time, the standard medical practice was to offer the mother varicellazoster immunoglobulin (VZIG) to boost her defence to the virus. The appellant’s mother however was not offered this treatment and contracted chickenpox resulting the appellant’s condition...

Phenytoin metabolism by human cytochrome P450 : involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation

The anticonvulsant phenytoin (5,5-diphenylhydantoin) provokes a skin rash in 5 to 10% of patients, which heralds the start of an idiosyncratic reaction that may result from covalent modification of normal self proteins by reactive drug metabolites. Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins. The aim of this study was to determine which P450s catalyze HPPH metabolism to the catechol, proposed to be the final enzymatic step in phenytoin bioactivation. Recombinant human P450s were coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. Novel bicistronic expression vectors were constructed for P450 2C19 and the three major variants of P450 2C9, i.e., 2C9*1, 2C9*2, and 2C9*3. HPPH metabolism and covalent adduct formation were assessed in parallel. P450 2C19 was the most effective catalyst of HPPH oxidation to the catechol metabolite and was also associated with the highest levels of covalent adduct formation. P450 3A4, 3A5, 3A7, 2C9*1, and 2C9*2 also catalyzed bioactivation of HPPH, but to a lesser extent. Fluorographic analysis showed that the major targets of adduct formation in bacterial membranes were the catalytic P450 forms, as suggested from experiments with human liver microsomes. These results suggest that P450 2C19 and other forms from the 2C and 3A subfamilies may be targets as well as catalysts of drug-protein adduct formation from phenytoin.

An investigation of schizotypy in injecting amphetamine users

A fully dimensional view of psychiatric disorder conceptualises schizotypy as both a continuous personality trait and an underlying vulnerability to the development of psychotic illness. Such a model would predict that the structure of schizotypal traits would closely parallel the structure of schizophrenia or psychosis. This was investigated in injecting amphetamine users (N = 322), a clinical population who have high rates of acute psychotic episodes and subclinical schizotypal experiences. Schizotypy was assessed using the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), and psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Using confirmatory factor analysis, O-LIFE subscale scores were mapped onto latent variables with their more clinical counterparts from the BPRS. A four-factor model comprising positive schizotypy, disorganisation, negative schizotypy, and disinhibition provided the best model fit, consistent with prior research into the structure of schizotypy. The model provided a good fit to the data, lending support to the theory that schizotypy and psychotic symptoms map onto common underlying dimensions.

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting A hospital alcohol and drug out-patient clinic. Participants Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings Positive (β = −0.29, P < 0.001) and negative (β = −0.19, P < 0.001) cannabis outcome expectancies were associated significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully mediated the association between negative expectancy and weekly consumption [95% confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of positive expectancy on weekly consumption (95% CI = 0.06, 0.17). Conclusions Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief that he or she can abstain from cannabis use) mediates part of the association between cannabis outcome expectancies (perceived consequences of cannabis use) and cannabis use.

From “anytime, anywhere” to “here and now”: place and time restrictions in mobile narratives to enhance situated engagement of mobile users

The usage of the mobile Internet has increased tremendously within the last couple of years, and thereby the vision of accessing information anytime, anywhere has become more realistic and a dominant design principle for providing content. However, this study challenges this paradigm of unlimited and unrestricted access, and explores the question whether constraints and restrictions can positively influence the motivation and enticement of mobile users to engage with location-specific content. Restrictions, such as a particular time or location that gives a user access to content, may be used to foster participation and engagement, as well as to support content production and to enhance the user’s experience. In order to explore this, a Mobile Narrative and a Narrative Map have been created. For the former, the access to individual chapters of the story was restricted. Authors can specify constraints, such as a location or time, which need to be met by the reader if they want to read the story. This concept allows creative writers of the story to exploit the fact that the reader’s context is known, by intensifying the user experience and integrating this knowledge into the writing process. The latter, the Narrative Map, provides users with extracts from stories or information snippets about authors at relevant locations. In both concepts, a feedback channel was also integrated, on which location, time, and size constraints were imposed. In a user-centred design process involving authors and potential readers, those concepts have been implemented, followed by an evaluation comprising four user studies. The results show that restrictions and constraints can indeed lead to more enticing and engaging user experiences, and restricted contribution opportunities can lead to a higher motivation to participate as well as to an improved quality of submissions. These findings are relevant for future developments in the area of mobile narratives and creative writing, as well as for common mobile services that aim for enticing user experiences.

Cross-cultural web user interface design for Indigenous internet users

This project investigated 1) Australian web designers’ cultural perceptions towards Australian Indigenous users and 2) Australian Indigenous cultural features in terms of user interface design. In doing so, it reviews the literature of cross-cultural user interface design by focusing on feasible models and arguments to articulate and integrate Australian Indigenous Internet users’ cultural needs of web user interface. The online survey results collected from 101 Indigenous users and 126 Web designers showed a distinctive difference between them on the integration of Indigenous users' cultural in Web sites. The interview data collected from 14 Indigenous users and 14 web designers suggested practical approaches to the design implications of Indigenous culture.

Identifying the Events That Connect Social Media Users : Charting Follower Accession on Twitter

Twitter is the focus of much research attention, both in traditional academic circles and in commercial market and media research, as analytics give increasing insight into the performance of the platform in areas as diverse as political communication, crisis management, television audiencing and other industries. While methods for tracking Twitter keywords and hashtags have developed apace and are well documented, the make-up of the Twitter user base and its evolution over time have been less understood to date. Recent research efforts have taken advantage of functionality provided by Twitter's Application Programming Interface to develop methodologies to extract information that allows us to understand the growth of Twitter, its geographic spread and the processes by which particular Twitter users have attracted followers. From politicians to sporting teams, and from YouTube personalities to reality television stars, this technique enables us to gain an understanding of what prompts users to follow others on Twitter. This article outlines how we came upon this approach, describes the method we adopted to produce accession graphs and discusses their use in Twitter research. It also addresses the wider ethical implications of social network analytics, particularly in the context of a detailed study of the Twitter user base.