Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

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.

Correlation between p-GaN growth environment with electrical and optical properties of blue LEDs

Two blue (450 nm) light–emitting diodes (LED), which only differ in top p-GaN layer growth conditions, were comparatively investigated. I-V, C-V, TLM, Electroluminescence (EL) and Photoluminescence (PL) techniques were applied to clarify a correlation between MOCVD carrier gas and internal properties. The A-structure grown in the pure N2 environment demonstrated better parameters than the B-structure grown in the N2/H2 (1:1) gas mixture. The mixed growth atmosphere leaded to an increase of sheet resistances of p-GaN layer. EL and PL measurements confirmed the advantage of the pure N2 utilization, and C(VR) measurement pointed the increase of static charge concentration near the p-GaN interface in the B structure.

Bioactive sol-gel glasses at the atomic scale:the complementary use of advanced probe and computer modeling methods

Sol-gel-synthesized bioactive glasses may be formed via a hydrolysis condensation reaction, silica being introduced in the form of tetraethyl orthosilicate (TEOS), and calcium is typically added in the form of calcium nitrate. The synthesis reaction proceeds in an aqueous environment; the resultant gel is dried, before stabilization by heat treatment. These materials, being amorphous, are complex at the level of their atomic-scale structure, but their bulk properties may only be properly understood on the basis of that structural insight. Thus, a full understanding of their structure-property relationship may only be achieved through the application of a coherent suite of leading-edge experimental probes, coupled with the cogent use of advanced computer simulation methods. Using as an exemplar a calcia-silica sol-gel glass of the kind developed by Larry Hench, in the memory of whom this paper is dedicated, we illustrate the successful use of high-energy X-ray and neutron scattering (diffraction) methods, magic-angle spinning solid-state NMR, and molecular dynamics simulation as components to a powerful methodology for the study of amorphous materials.

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.

Heritage and innovative learning approaches:an alternative approach to engineering education

Over recent years, the role of engineering in promoting a sustainable society has received much public attention [1] with particular emphasis given to the need to promote the future prosperity and security of society through the recruitment and education of more engineers [2,3]. From an employment perspective, the Leitch Review [4] suggested that ‘generic’ transferable employability skills development should constitute a more substantial part of university education. This paper argues that the global drivers impacting engineering education [5] correlate strongly to those underpinning the Leitch review, therefore the question of how to promote transferable employability skills within the wider engineering curriculum is increasingly relevant. By exploring the use of heritage in the engineering curriculum as a way to promote learning and engage students, a less familiar approach to study is discussed. This approach moves away from stereotypical notions of the use of information technology as representing the pinnacle of innovation in education. Taking the student experience as its starting point, the paper draws upon the findings of an exploratory study critically analysing the pedagogical value of using heritage in engineering education. It discusses a teaching approach in which engineering students are taken out of their ‘comfort zone’ - away from the classroom, laboratory and computer, to a heritage site some 100 miles away from the university. The primary learning objective underpinning this approach is to develop students’ transferable skills by encouraging them to consider how to apply theoretical concepts to a previously unexplored situation. By reflecting upon students’ perceptions of the value of this approach, and by identifying how heritage may be utilised as an innovative learning and teaching approach in engineering education, this paper makes a notable contribution to current pedagogical debates in the discipline.

Getting round pegs into round holes:getting students onto the right engineering programme

Aston University offers a Foundation year in Engineering and Applied Science. The purpose of this programme is to prepare people with the necessary skills and knowledge required to enrol on an undergraduate programme in Engineering and Applied Science. It is acknowledged there are many misconceptions as to what engineering is. This is further compounded by the lack of knowledge of the different engineering disciplines both by pre-university students and careers teachers [1]. In order to ameliorate this lack of knowledge, Aston University offers a unique programme where students are given the opportunity to have a ?taste? of four Engineering Disciplines: Mechanical Engineering, Electrical Engineering, Chemical Engineering and Computer Science. Alongside these ?taster? sessions, the students study a Professional Skills module where they are expected to keep a portfolio of skills. In their portfolios they comment on their strengths and weakness in relation to six skill areas: independent enquirer, self-manager, effective participator, creative thinker, reflective learner and team worker. The portfolio gives them the opportunity to perform a self-skills audit and identify areas where they have strengths and areas which require work to improve to become a competent professional engineer. They also have talks from engineers who discuss with them their careers and the different aspects of engineering. The purpose of the ?taster? sessions, portfolio and the talks are to encourage the students to critically examine their career aspirations and choose an engineering undergraduate programme which best suits their ambitions and potential skills. The feedback from students has been very positive. The ?taster? sessions have enabled them to make an informed choice as to the undergraduate programme they would like to study. The programme has given them the technical skills and knowledge to enrol on an undergraduate programme and also the skills and knowledge to be a successful learner.

Re-engineering construction communication in distance management framework

In an exploding and fluctuating construction market, managers are facing a challenge, which is how to manage business on a wider scale and to utilize modern developments in information technology to promote productivity. The extraordinary development of telecommunications and computer technology makes it possible for people to plan, lead, control, organize and manage projects from a distance without the need to be on site on a daily basis. A modern management known as distance management (DM) or remote management is emerging. Physical distance no longer determines the boundary of management since managers can now operate projects through virtual teams that organize manpower, material and production without face-to-face communication. What organization prototype could overcome psychological and physical barriers to reengineer a successful project through information technology? What criteria distinguishes the adapted way of communication of individual activities in a teamwork and assist the integration of an efficient and effective communication between face-to-face and a physical distance? The entire methodology has been explained through a case application on refuse incineration plant projects in Taiwan.

A combined neural network and DEA for measuring efficiency of large scale datasets

Data Envelopment Analysis (DEA) is one of the most widely used methods in the measurement of the efficiency and productivity of Decision Making Units (DMUs). DEA for a large dataset with many inputs/outputs would require huge computer resources in terms of memory and CPU time. This paper proposes a neural network back-propagation Data Envelopment Analysis to address this problem for the very large scale datasets now emerging in practice. Neural network requirements for computer memory and CPU time are far less than that needed by conventional DEA methods and can therefore be a useful tool in measuring the efficiency of large datasets. Finally, the back-propagation DEA algorithm is applied to five large datasets and compared with the results obtained by conventional DEA.

Reliability:its implications in production systems design

Research on production systems design has in recent years tended to concentrate on ‘software’ factors such as organisational aspects, work design, and the planning of the production operations. In contrast, relatively little attention has been paid to maximising the contributions made by fixed assets, particularly machines and equipment. However, as the cost of unproductive machine time has increased, reliability, particularly of machine tools, has become ever more important. Reliability theory and research has traditionally been based in the main on electrical and electronic equipment whereas mechanical devices, especially machine tools, have not received sufficiently objective treatment. A recently completed research project has considered the reliability of machine tools by taking sample surveys of purchasers, maintainers and manufacturers. Breakdown data were also collected from a number of engineering companies and analysed using both manual and computer techniques. Results obtained have provided an indication of those factors most likely to influence reliability and which in turn could lead to improved design and selection of machine tool systems. Statistical analysis of long-term field data has revealed patterns of trends of failure which could help in the design of more meaningful maintenance schemes.

Process integration and improvement using systemic diagrams and a human-centred approach

If product cycle time reduction is the mission, and the multifunctional team is the means of achieving the mission, what then is the modus operandi by which this means is to accomplish its mission? This paper asserts that a preferred modus operandi for the multifunctional team is to adopt a process-oriented view of the manufacturing enterprise, and for this it needs the medium of a process map [16] The substance of this paper is a methodology which enables the creation of such maps Specific examples of process models drawn from the product develop ment life cycle are presented and described in order to support the methodology's integrity and value The specific deliverables we have so far obtained are a methodology for process capture and analysis, a collection of process models spanning the product development cycle, and, an engineering handbook which hosts these models and presents a computer-based means of navigating through these processes in order to allow users a better understanding of the nature of the business, their role in it, and why the job that they do benefits the work of the company We assert that this kind of thinking is the essence of concurrent engineering implementation, and further that the systemigram process models uniquely stim ulate and organise such thinking.

Bioreaction and separation in batch chromatographic columns

The objective of this work has been to study the behaviour and performance of a batch chromatographic column under simultaneous bioreaction and separation conditions for several carbohydrate feedstocks. Four bioreactions were chosen, namely the hydrolysis of sucrose to glucose and fructose using the enzyme invertase, the hydrolysis of inulin to fructose and glucose using inulinase, the hydrolysis of lactose to glucose and galactose using lactase and the isomerization of glucose to fructose using glucose isomerase. The chromatographic columns employed were jacketed glass columns ranging from 1 m to 2 m long and the internal diameter ranging from 0.97 cm to 1.97 cm. The stationary phase used was a cation exchange resin (PUROLITE PCR-833) in the Ca2+ form for the hydrolysis and the Mg2+ form for the isomerization reactions. The mobile phase used was a diluted enzyme solution which was continuously pumped through the chromatographic bed. The substrate was injected at the top of the bed as a pulse. The effect of the parameters pulse size, the amount of substrate solution introduced into the system corresponding to a percentage of the total empty column volume (% TECV), pulse concentration, eluent flowrate and the enzyme activity of the eluent were investigated. For the system sucrose-invertase complete conversions of substrate were achieved for pulse sizes and pulse concentrations of up to 20% TECV and 60% w/v, respectively. Products with purity above 90% were obtained. The enzyme consumption was 45% of the amount theoretically required to produce the same amount of product as in a conventional batch reactor. A value of 27 kg sucrose/m3 resin/h for the throughput of the system was achieved. The systematic investigation of the factors affecting the performance of the batch chromatographic bioreactor-separator was carried out by employing a factorial experimental procedure. The main factors affecting the performance of the system were the flowrate and enzyme activity. For the system inulin-inulinase total conversions were also obtained for pulses sizes of up to 20 % TECV and a pulse concentration of 10 % w/v. Fructose rich fractions with 100 % purity and representing up to 99.4 % of the total fructose generated were obtained with an enzyme consumption of 32 % of the amount theoretically required to produce the same amount of product in a conventional batch reactor. The hydrolysis of lactose by lactase was studied in the glass columns and also in an SCCR-S unit adapted for batch operation, in co-operation with Dr. Shieh, a fellow researcher in the Chemical Engineering and Applied Chemistry Department at Aston University. By operating at up to 30 % w/v lactose feed concentrations complete conversions were obtained and the purities of the products generated were above 90%. An enzyme consumption of 48 % of the amount theoretically required to produce the same amount of product in a conventional batch reactor was achieved. On working with the system glucose-glucose isomerase, which is a reversible reaction, the separation obtained with the stationary phase conditioned in the magnesium form was very poor although the conversion obtained was compatible with those for conventional batch reactors. By working with a mixed pulse of enzyme and substrate, up to 82.5 % of the fructose generated with a purity of 100 % was obtained. The mathematical modelling and computer simulation of the batch chromatographic bioreaction-separation has been performed on a personal computer. A finite difference method was used to solve the partial differential equations and the simulation results showed good agreement with the experimental results.

Can computer-based testing achieve quality and efficiency in assessment?

This paper reports findings of a two year study concerning the development and implementation of a general-purpose computer-based assessment (CBA) system at a UK University. Data gathering took place over a period of nineteen months, involving a number of formative and summative assessments. Approximately 1,000 students, drawn from undergraduate courses, were involved in the exercise. The techniques used in gathering data included questionnaires, observation, interviews and an analysis of student scores in both conventional examinations and computer-based assessments. Comparisons with conventional assessment methods suggest that the use of CBA techniques may improve the overall performance of students. However it is clear that the technique must not be seen as a "quick fix" for problems such as rising student numbers. If one accepts that current systems test only a relatively narrow range of skills, then the hasty implementation of CBA systems will result in a distorted and inaccurate view of student performance. In turn, this may serve to reduce the overall quality of courses and - ultimately - detract from the student learning experience. On the other hand, if one adopts a considered and methodical approach to computer-based assessment, positive benefits might include increased efficiency and quality, leading to improved student learning.

Intracavity dynamics for power and energy enhancement in mode-locked lasers

We present a theoretical description of the generation of ultra-short, high-energy pulses in two laser cavities driven by periodic spectral filtering or dispersion management. Critical in driving the intra-cavity dynamics is the nontrivial phase profiles generated and their periodic modification from either spectral filtering or dispersion management. For laser cavities with a spectral filter, the theory gives a simple geometrical description of the intra-cavity dynamics and provides a simple and efficient method for optimizing the laser cavity performance. In the dispersion managed cavity, analysis shows the generated self-similar behavior to be governed by the porous media equation with a rapidly-varying, mean-zero diffusion coefficient whose solution is the well-known Barenblatt similarity solution with parabolic profile.