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.

The impact of privatisation and regulation on the water and sewerage industry in England and Wales:a translog cost function approach

After the ten Regional Water Authorities (RWAs) of England and Wales were privatized in November 1989, the successor Water and Sewerage Companies (WASCs) faced a new regulatory regime that was designed to promote economic efficiency while simultaneously improving drinking water and environmental quality. As legally mandated quality improvements necessitated a costly capital investment programme, the industry's economic regulator, the Office of Water Services (Ofwat), implemented a retail price index (RPI)+K pricing system, which was designed to compensate the WASCs for their capital investment programme while also encouraging gains in economic efficiency. In order to analyse jointly the impact of privatization, as well as the impact of increasingly stringent economic and environmental regulation on the WASCs' economic performance, this paper estimates a translog multiple output cost function model for the period 1985–1999. Given the significant costs associated with water quality improvements, the model is augmented to include the impact of drinking water quality and environmental quality on total costs. The model is then employed to determine the extent of scale and scope economies in the water and sewerage industry, as well as the impact of privatization and economic regulation on economic efficiency.

Outsourcing and offshoring engineering projects:understanding the value, sourcing models, and coordination practices

In this paper, we review recent developments in the field of outsourcing and offshoring and the implications for engineering management. We examine three aspects involved in outsourcing and offshoring, namely, sourcing models, coordination, and value extracted from outsourcing projects. We conclude that additional research is needed on recent trends in outsourcing and the impact of such change process on the practice of engineering management. © 2011 IEEE.

Adhesive wear of modern and traditional engineering coatings

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Experiments for CFD-modelling of cooling water and Insulation debris two-phase flow phenomena during loss of coolant accidents

The knowledge of insulation debris generation and transport gains in importance regarding reactor safety research for PWR and BWR. The insulation debris released near the break consists of a mixture of very different fibres and particles concerning size, shape, consistence and other properties. Some fraction of the released insulation debris will be transported into the reactor sump where it may affect emergency core cooling. Experiments are performed to blast original samples of mineral wool insulation material by steam under original thermal-hydraulic break conditions of BWR. The gained fragments are used as initial specimen for further experiments at acrylic glass test facilities. The quasi ID-sinking behaviour of the insulation fragments are investigated in a water column by optical high speed video techniques and methods of image processing. Drag properties are derived from the measured sinking velocities of the fibres and observed geometric parameters for an adequate CFD modelling. In the test rig "Ring line-II" the influence of the insulation material on the head loss is investigated for debris loaded strainers. Correlations from the filter bed theory are adapted with experimental results and are used to model the flow resistance depending on particle load, filter bed porosity and parameters of the coolant flow. This concept also enables the simulation of a particular blocked strainer with CFDcodes. During the ongoing work further results of separate effect and integral experiments and the application and validation of the CFD-models for integral test facilities and original containment sump conditions are expected.

Profit, productivity and price performance changes in the water and sewerage industry:an empirical application for England and Wales

This paper aims to analyse the impact of regulation in the financial performance of the Water and Sewerage companies (WaSCs) in England and Wales over the period 1991–2008. In doing so, a panel index approach is applied across WaSCs over time to decompose unit-specific index number-based profitability growth as a function of the profitability, productivity and price performance growth achieved by benchmark firms, and the catch up to the benchmark firm achieved by less productive firms. The results indicated that after 2000 there is a steady decline in average price performance, while productivity improves resulting in a relatively stable economic profitability. It is suggested that the English and Welsh water regulator is now more focused on passing productivity benefits to consumers, and maintaining stable profitability than it was in earlier regulatory periods. This technique is of great interest for regulators to evaluate the effectiveness of regulation and companies to identify the determinants of profit change and improve future performance, even if sample sizes are limited.

University-led innovative and inspirational engineering education

The UK Government and large employers have recognised the skills gap between learners leaving the education system and the requirements of employers. The current system is seen to be failing significant numbers of learners and has been accused of schooling but not educating our young people. University-led technical colleges are one part of the solution being developed to provide outstanding engineering education. This paper focusses on the learning experience that the Aston University Engineering Academy, the first University-led University Technical College (UTC), has created for entrants to the Engineering Academy in September 2012, when it opens in brand new buildings next to the University. The overall aim is to produce technically literate young people that have business and enterprise skills as well as insight into the diverse range of opportunities in Engineering and Technical disciplines. The project has brought University staff and students together with employers and Academy staff to optimise the engineering education that they will receive. The innovative model presented has drawn on research from across the world in the implementation of this new type of school, as well as educational practices from the USA and the Scandinavian countries. The resulting curriculum is authentic and exciting and expands the University model of problem-based learning and placements into the secondary school environment. The benefits of this close partnership for University staff and students, the employers and the Academy staff are expanded on and the paper concludes with a prediction of progression routes from the Academy.

Microporous polycaprolactone matrices for drug delivery and tissue engineering:the release behaviour of bioactives having extremes of aqueous solubility

Microporous polycaprolactone (PCL) matrices loaded with hydrophobic steroidal drugs or a hydrophilic drug - pilocarpine hydrochloride - were produced by precipitation casting using solutions of PCL in acetone. The efficiency of steroid incorporation in the final matrix (progesterone (56 %) testosterone (46 %) dexamethasone (80 %)) depended on the nature of the drug initially co-dissolved in the PCL solution. Approximately 90 % w/w of the initial load of progesterone, 85 % testosterone and 50 % dexamethasone was released from the matrices in PBS at 37°C over 8 days. Pilocarpine hydrochloride (PH)-loaded PCL matrices, prepared by dispersion of powder in PCL solution, released 70-90 % of the PH content over 12 days in PBS. Application of the Higuchi model revealed that the kinetics of steroid and PH release were consistent with a Fickian diffusion mechanism with corresponding diffusion coefficients of 5.8 × 10-9 (progesterone), 3.9 × 10 -9 (testosterone), 7.1 × 10-10 (dexamethasone) and 22 × 10-8 cm2/s (pilocarpine hydrochloride). The formulation techniques described are expected to be useful for production of implantable, insertable and topical devices for sustained delivery of a range of bioactive molecules of interest in drug delivery and tissue engineering.

A micro industry with closed energy and water cycles for sustainable rural development

Sustainable development requires combining economic viability with energy and environment conservation and ensuring social benefits. It is conceptualized that for designing a micro industry for sustainable rural industrialization, all these aspects should be integrated right up front. The concept includes; (a) utilization of local produce for value addition in a cluster of villages and enhancing income of the target population; (b) use of renewable energy and total utilization of energy generated by co and trigeneration (combining electric power production with heat utilization for heating and cooling); (c) conservation of water and complete recycling of effluents; (d) total utilization of all wastes for achieving closure towards a zero waste system. Enhanced economic viability and sustainability is achieved by integration of appropriate technologies into the industrial complex. To prove the concept, a model Micro Industrial Complex (MIC) has been set up in a semi arid desert region in Rajasthan, India at village Malunga in Jodhpur district. A biomass powered boiler and steam turbine system is used to generate 100-200 KVA of electric power and high energy steam for heating and cooling processes downstream. The unique feature of the equipment is a 100-150 kW back-pressure steam turbine, utilizing 3-4 tph (tonnes per hour) steam, developed by M/s IB Turbo. The biomass boiler raises steam at about 20 barg 3 tph, which is passed through a turbine to yield about 150 kW of electrical power. The steam let out at a back pressure of 1-3 barg has high exergy and this is passed on as thermal energy (about 2 MW), for use in various applications depending on the local produce and resources. The biomass fuel requirement for the boiler is 0.5-0.75 tph depending on its calorific value. In the current model, the electricity produced is used for running an oil expeller to extract castor oil and the castor cake is used as fuel in the boiler. The steam is used in a Multi Effect Distillation (MED) unit for drinking water production and in a Vapour Absorption Machine (VAM) for cooling, for banana ripening application. Additional steam is available for extraction of herbs such as mint and processing local vegetables. In this paper, we discuss the financial and economic viability of the system and show how the energy, water and materials are completely recycled and how the benefits are directed to the weaker sections of the community.