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.

Using process-oriented holonic (PrOH) modelling to increase understanding of information systems

Methodologies for understanding business processes and their information systems (IS) are often criticized, either for being too imprecise and philosophical (a criticism often levied at softer methodologies) or too hierarchical and mechanistic (levied at harder methodologies). The process-oriented holonic modelling methodology combines aspects of softer and harder approaches to aid modellers in designing business processes and associated IS. The methodology uses holistic thinking and a construct known as the holon to build process descriptions into a set of models known as a holarchy. This paper describes the methodology through an action research case study based in a large design and manufacturing organization. The scientific contribution is a methodology for analysing business processes in environments that are characterized by high complexity, low volume and high variety where there are minimal repeated learning opportunities, such as large IS development projects. The practical deliverables from the project gave IS and business process improvements for the case study company.

A design and implementation methodology for high variety electronics assembly systems

Small indigenous manufacturers of electronic equipment are coming under increasingly severe pressure to adopt a strong defensive position against large multinational and Far Eastern companies. A common response to this threat has been for these firms to adopt a 'market driven' business strategy based on quality and customer service, rather than a 'technology led' strategy which uses technical specification and price to compete. To successfully implement this type of strategy there is a need for production systems to be redesigned to suit the new demands of marketing. Increased range and fast response require economy of scope rather t ban economy or scale while the organisation's culture must promote quality and process consciousness. This paper describes the 'Modular Assembly Cascade' concept which addresses these needs by applying the principles of flexible manufacturing (FMS) and just in time (,JlT) to electronics assembly. A methodology for executing the concept is also outlined. This is called DRAMA (Design Houtirw !'or· Adopting Modular Assembly).

Audience design in the police interview:the interactional and judicial consequences of audience orientation

Police-suspect interviews in England & Wales are a multi-audience, multi-purpose, transcontextual mode of discourse. They are conducted as part of the initial investigation into a crime, but are subsequently recontextualised through the judicial process, ultimately being presented in court as evidence against the interviewee. The communicative challenges posed by multiple future audiences are investigated by applying Bell’s (1984) audience design model to the police interview, and the resulting "poor fit" demonstrates why this context is discursively counter-intuitive to participants. Further, data analysis indicates that interviewer and interviewee, although ostensibly addressing each other, may orientate to different audiences, with potentially serious consequences. As well as providing new insight into police-suspect interview interaction, this article seeks to extend understanding of the influence of audience on interaction at the discourse level, and to contribute to the development of theoretical models for contexts with multiple or asynchronous audiences.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.

Design and designing:a critical introduction

Design and Designing provides a broad and critical understanding of what is essentially a practical subject. Designing today is less a craft and more a part of the knowledge economy. It's all about knowing how to acquire knowledge and how to apply it creatively. Design and Designing covers the design process, modelling and drawing, working with clients, production and consumption, sustainability, professional practice and design futures. Chapters are written by expert teachers and practitioners from around the globe, each presenting an accessible and engaging overview of their field of design. Every chapter is highly illustrated with a combination of images and information boxes, which extend or highlight key material. Each section concludes with a design project, a hands-on activity for the reader. Design and Designing covers the full spectrum of design types, from graphic communication to product design, from fashion to games design, setting every type in its aesthetic, ethical and social contexts. With this essential book, readers will learn from today's best practice and best thinking in design, they will develop a critical sense, and become the designers of tomorrow.

A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes:design and methodology [ISRCTN78467674]

Background: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.

Knowledge-based system for casting process selection

Design of casting entails the knowledge of various interacting factors that are unique to casting process, and, quite often, product designers do not have the required foundry-specific knowledge. Casting designers normally have to liaise with casting experts in order to ensure the product designed is castable and the optimum casting method is selected. This two-way communication results in long design lead times, and lack of it can easily lead to incorrect casting design. A computer-based system at the discretion of a design engineer can, however, alleviate this problem and enhance the prospect of casting design for manufacture. This paper proposes a knowledge-based expert system approach to assist casting product designers in selecting the most suitable casting process for specified casting design requirements, during the design phase of product manufacture. A prototype expert system has been developed, based on production rules knowledge representation technique. The proposed system consists of a number of autonomous but interconnected levels, each dealing with a specific group of factors, namely, casting alloy, shape and complexity parameters, accuracy requirements and comparative costs, based on production quantity. The user interface has been so designed to allow the user to have a clear view of how casting design parameters affect the selection of various casting processes at each level; if necessary, the appropriate design changes can be made to facilitate the castability of the product being designed, or to suit the design to a preferred casting method.

Simulation process of biodiesel production over heterogeneous catalysts

Biodiesel production is a very promising area due to the relevance that it is an environmental-friendly diesel fuel alternative to fossil fuel derived diesel fuels. Nowadays, most industrial applications of biodiesel production are performed by the transesterification of renewable biological sources based on homogeneous acid catalysts, which requires downstream neutralization and separation leading to a series of technical and environmental problems. However, heterogeneous catalyst can solve these issues, and be used as a better alternative for biodiesel production. Thus, a heuristic diffusion-reaction kinetic model has been established to simulate the transesterification of alkyl ester with methanol over a series of heterogeneous Cs-doped heteropolyacid catalysts. The novelty of this framework lies in detailed modeling of surface reacting kinetic phenomena and integrating that with particle-level transport phenomena all the way through to process design and optimisation, which has been done for biodiesel production process for the first time. This multi-disciplinary research combining chemistry, chemical engineering and process integration offers better insights into catalyst design and process intensification for the industrial application of Cs-doped heteropolyacid catalysts for biodiesel production. A case study of the transesterification of tributyrin with methanol has been demonstrated to establish the effectiveness of this methodology.

The UK MPharm (1) - are we over reliant on traditional teaching methods?

Introduction-The design of the UK MPharm curriculum is driven by the Royal Pharmaceutical Society of Great Britain (RPSGB) accreditation process and the EU directive (85/432/EEC).[1] Although the RPSGB is informed about teaching activity in UK Schools of Pharmacy (SOPs), there is no database which aggregates information to provide the whole picture of pharmacy education within the UK. The aim of the teaching, learning and assessment study [2] was to document and map current programmes in the 16 established SOPs. Recent developments in programme delivery have resulted in a focus on deep learning (for example, through problem based learning approaches) and on being more student centred and less didactic through lectures. The specific objectives of this part of the study were (a) to quantify the content and modes of delivery of material as described in course documentation and (b) having categorised the range of teaching methods, ask students to rate how important they perceived each one for their own learning (using a three point Likert scale: very important, fairly important or not important). Material and methods-The study design compared three datasets: (1) quantitative course document review, (2) qualitative staff interview and (3) quantitative student self completion survey. All 16 SOPs provided a set of their undergraduate course documentation for the year 2003/4. The documentation variables were entered into Excel tables. A self-completion questionnaire was administered to all year four undergraduates, using a pragmatic mixture of methods, (n=1847) in 15 SOPs within Great Britain. The survey data were analysed (n=741) using SPSS, excluding non-UK students who may have undertaken part of their studies within a non-UK university. Results and discussion-Interviews showed that individual teachers and course module leaders determine the choice of teaching methods used. Content review of the documentary evidence showed that 51% of the taught element of the course was delivered using lectures, 31% using practicals (includes computer aided learning) and 18% small group or interactive teaching. There was high uniformity across the schools for the first three years; variation in the final year was due to the project. The average number of hours per year across 15 schools (data for one school were not available) was: year 1: 408 hours; year 2: 401 hours; year 3: 387 hours; year 4: 401 hours. The survey showed that students perceived lectures to be the most important method of teaching after dispensing or clinical practicals. Taking the very important rating only: 94% (n=694) dispensing or clinical practicals; 75% (n=558) lectures; 52% (n=386) workshops, 50% (n=369) tutorials, 43% (n=318) directed study. Scientific laboratory practices were rated very important by only 31% (n=227). The study shows that teaching of pharmacy to undergraduates in the UK is still essentially didactic through a high proportion of formal lectures and with high levels of staff-student contact. Schools consider lectures still to be the most cost effective means of delivering the core syllabus to large cohorts of students. However, this does limit the scope for any optionality within teaching, the scope for small group work is reduced as is the opportunity to develop multi-professional learning or practice placements. Although novel teaching and learning techniques such as e-learning have expanded considerably over the past decade, schools of pharmacy have concentrated on lectures as the best way of coping with the huge expansion in student numbers. References [1] Council Directive. Concerning the coordination of provisions laid down by law, regulation or administrative action in respect of certain activities in the field of pharmacy. Official Journal of the European Communities 1985;85/432/EEC. [2] Wilson K, Jesson J, Langley C, Clarke L, Hatfield K. MPharm Programmes: Where are we now? Report commissioned by the Pharmacy Practice Research Trust., 2005.

Online-questionnaire design:establishing guidelines and evaluating existing eupport

As a new medium for questionnaire delivery, the internet has the potential to revolutionise the survey process. Online (web-based) questionnaires provide several advantages over traditional survey methods in terms of cost, speed, appearance, flexibility, functionality, and usability [1, 2]. For instance, delivery is faster, responses are received more quickly, and data collection can be automated or accelerated [1- 3]. Online-questionnaires can also provide many capabilities not found in traditional paper-based questionnaires: they can include pop-up instructions and error messages; they can incorporate links; and it is possible to encode difficult skip patterns making such patterns virtually invisible to respondents. Like many new technologies, however, online-questionnaires face criticism despite their advantages. Typically, such criticisms focus on the vulnerability of online-questionnaires to the four standard survey error types: namely, coverage, non-response, sampling, and measurement errors. Although, like all survey errors, coverage error (“the result of not allowing all members of the survey population to have an equal or nonzero chance of being sampled for participation in a survey” [2, pg. 9]) also affects traditional survey methods, it is currently exacerbated in online-questionnaires as a result of the digital divide. That said, many developed countries have reported substantial increases in computer and internet access and/or are targeting this as part of their immediate infrastructural development [4, 5]. Indicating that familiarity with information technologies is increasing, these trends suggest that coverage error will rapidly diminish to an acceptable level (for the developed world at least) in the near future, and in so doing, positively reinforce the advantages of online-questionnaire delivery. The second error type – the non-response error – occurs when individuals fail to respond to the invitation to participate in a survey or abandon a questionnaire before it is completed. Given today’s societal trend towards self-administration [2] the former is inevitable, irrespective of delivery mechanism. Conversely, non-response as a consequence of questionnaire abandonment can be relatively easily addressed. Unlike traditional questionnaires, the delivery mechanism for online-questionnaires makes estimation of questionnaire length and time required for completion difficult1, thus increasing the likelihood of abandonment. By incorporating a range of features into the design of an online questionnaire, it is possible to facilitate such estimation – and indeed, to provide respondents with context sensitive assistance during the response process – and thereby reduce abandonment while eliciting feelings of accomplishment [6]. For online-questionnaires, sampling error (“the result of attempting to survey only some, and not all, of the units in the survey population” [2, pg. 9]) can arise when all but a small portion of the anticipated respondent set is alienated (and so fails to respond) as a result of, for example, disregard for varying connection speeds, bandwidth limitations, browser configurations, monitors, hardware, and user requirements during the questionnaire design process. Similarly, measurement errors (“the result of poor question wording or questions being presented in such a way that inaccurate or uninterpretable answers are obtained” [2, pg. 11]) will lead to respondents becoming confused and frustrated. Sampling, measurement, and non-response errors are likely to occur when an online-questionnaire is poorly designed. Individuals will answer questions incorrectly, abandon questionnaires, and may ultimately refuse to participate in future surveys; thus, the benefit of online questionnaire delivery will not be fully realized. To prevent errors of this kind2, and their consequences, it is extremely important that practical, comprehensive guidelines exist for the design of online questionnaires. Many design guidelines exist for paper-based questionnaire design (e.g. [7-14]); the same is not true for the design of online questionnaires [2, 15, 16]. The research presented in this paper is a first attempt to address this discrepancy. Section 2 describes the derivation of a comprehensive set of guidelines for the design of online-questionnaires and briefly (given space restrictions) outlines the essence of the guidelines themselves. Although online-questionnaires reduce traditional delivery costs (e.g. paper, mail out, and data entry), set up costs can be high given the need to either adopt and acquire training in questionnaire development software or secure the services of a web developer. Neither approach, however, guarantees a good questionnaire (often because the person designing the questionnaire lacks relevant knowledge in questionnaire design). Drawing on existing software evaluation techniques [17, 18], we assessed the extent to which current questionnaire development applications support our guidelines; Section 3 describes the framework used for the evaluation, and Section 4 discusses our findings. Finally, Section 5 concludes with a discussion of further work.

Using a systems approach in logistics design and planning

The international economic and business environment continues to develop at a rapid rate. Increasing interactions between economies, particularly between Europe and Asia, has raised many important issues regarding transport infrastructure, logistics and broader supply chain management. The potential exists to further stimulate trade provided that these issues are addressed in a logical and systematic manner. However, if this potential is to be realised in practice there is a need to re-evaluate current supply chain configurations. A mismatch currently exists between the technological capability and the supply chain or logistical reality. This mismatch has sharpened the focus on the need for robust approaches to supply chain re-engineering. Traditional approaches to business re-engineering have been based on manufacturing systems engineering and business process management. A recognition that all companies exist as part of bigger supply chains has fundamentally changed the focus of re-engineering. Inefficiencies anywhere in a supply chain result in the chain as a whole being unable to reach its true competitive potential. This reality, combined with the potentially radical impact on business and supply chain architectures of the technologies associated with electronic business, requires organisations to adopt innovative approaches to supply chain analysis and re-design. This paper introduces a systems approach to supply chain re-engineering which is aimed at addressing the challenges which the evolving business environment brings with it. The approach, which is based on work with a variety of both conventional and electronic supply chains, comprises underpinning principles, a methodology and guidelines on good working practice, as well as a suite of tools and techniques. The adoption of approaches such as that outlined in this paper helps to ensure that robust supply chains are designed and implemented in practice. This facilitates an integrated approach, with involvement of all key stakeholders throughout the design process.

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Incorporating Water Sensitive Urban Design (WSUD) practices into the planning context:the conceptual case for lot-scale developments

In recent decades, a number of sustainable strategies and polices have been created to protect and preserve our water environments from the impacts of growing communities. The Australian approach, Water Sensitive Urban Design (WSUD), defined as the integration of urban planning and design with the urban water cycle management, has made considerable advances on design guidelines since 2000. WSUD stormwater management systems (e.g. wetlands, bioretentions, porous pavement etc), also known as Best Management Practices (BMPs) or Low Impact Development (LID), are slowly gaining popularity across Australia, the USA and Europe. There have also been significant improvements in how to model the performance of the WSUD technologies (e.g. MUSIC software). However, the implementation issues of these WSUD practices are mainly related to ongoing institutional capacity. Some of the key problems are associated with a limited awareness of urban planners and designers; in general, they have very little knowledge of these systems and their benefits to the urban environments. At the same time, hydrological engineers should have a better understanding of building codes and master plans. The land use regulations are equally as important as the physical site conditions for determining opportunities and constraints for implementing WSUD techniques. There is a need for procedures that can make a better linkage between urban planners and WSUD engineering practices. Thus, this paper aims to present the development of a general framework for incorporating WSUD technologies into the site planning process. The study was applied to lot-scale in the Melbourne region, Australia. Results show the potential space available for fitting WSUD elements, according to building requirements and different types of housing densities. © 2011 WIT Press.