The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum.

Strategies and therapeutic opportunities for the delivery of drugs to the esophagus

Targeting of drugs and therapies locally to the esophagus is an important objective in the development of new and more effective dosage forms. Therapies that are retained within the oral cavity for both local and systemic action have been utilized for many years, although delivery to the esophagus has been far less reported. Esophageal disease states, including infections, motility disorders, gastric reflux, and cancers, would all benefit from localized drug delivery. Therefore, research in this area provides significant opportunities. The key limitation to effective drug delivery within the esophagus is sufficient retention at this site coupled with activity profiles to correspond with these retention times; therefore, a suitable formulation needs to provide the drug in a ready-to-work form at the site of action during the rapid transit through this organ. A successfully designed esophageal-targeted system can overcome these obstacles. This review presents a range of dosage form approaches for targeting the esophagus, including bioadhesive liquids and orally retained lozenges, chewing gums, gels, and films, as well as endoscopically delivered therapeutics. The techniques used to measure efficacy both in vitro and in vivo are also discussed. Drug delivery is a growing driver within the pharmaceutical industry and offers benefits both in terms of clinical efficacy, as well as in market positioning, as a means of extending a drug's exclusivity and profitability. Emerging systems that can be used to target the esophagus are reported within this review, as well as the potential of alternative formulations that offer benefits in this exciting area.

Optimization of PCB component placements for the collect-and-place machines

This paper presents two hybrid genetic algorithms (HGAs) to optimize the component placement operation for the collect-and-place machines in printed circuit board (PCB) assembly. The component placement problem is to optimize (i) the assignment of components to a movable revolver head or assembly tour, (ii) the sequence of component placements on a stationary PCB in each tour, and (iii) the arrangement of component types to stationary feeders simultaneously. The objective of the problem is to minimize the total traveling time spent by the revolver head for assembling all components on the PCB. The major difference between the HGAs is that the initial solutions are generated randomly in HGA1. The Clarke and Wright saving method, the nearest neighbor heuristic, and the neighborhood frequency heuristic are incorporated into HGA2 for the initialization procedure. A computational study is carried out to compare the algorithms with different population sizes. It is proved that the performance of HGA2 is superior to HGA1 in terms of the total assembly time.

An integrated scheduling problem of PCB components on sequential pick-and-place machines:mathematical models and heuristic solutions

This paper formulates several mathematical models for determining the optimal sequence of component placements and assignment of component types to feeders simultaneously or the integrated scheduling problem for a type of surface mount technology placement machines, called the sequential pick-andplace (PAP) machine. A PAP machine has multiple stationary feeders storing components, a stationary working table holding a printed circuit board (PCB), and a movable placement head to pick up components from feeders and place them to a board. The objective of integrated problem is to minimize the total distance traveled by the placement head. Two integer nonlinear programming models are formulated first. Then, each of them is equivalently converted into an integer linear type. The models for the integrated problem are verified by two commercial packages. In addition, a hybrid genetic algorithm previously developed by the authors is adopted to solve the models. The algorithm not only generates the optimal solutions quickly for small-sized problems, but also outperforms the genetic algorithms developed by other researchers in terms of total traveling distance.

A heuristic approach for component scheduling on a high-speed PCB assembly machine

The collect-and-place machine is one of the most widely used placement machines for assembling electronic components on the printed circuit boards (PCBs). Nevertheless, the number of researches concerning the optimisation of the machine performance is very few. This motivates us to study the component scheduling problem for this type of machine with the objective of minimising the total assembly time. The component scheduling problem is an integration of the component sequencing problem, that is, the sequencing of component placements; and the feeder arrangement problem, that is, the assignment of component types to feeders. To solve the component scheduling problem efficiently, a hybrid genetic algorithm is developed in this paper. A numerical example is used to compare the performance of the algorithm with different component grouping approaches and different population sizes.

Component scheduling for chip shooter machines: a hybrid genetic algorithm approach

A chip shooter machine for electronic component assembly has a movable feeder carrier, a movable X–Y table carrying a printed circuit board (PCB), and a rotary turret with multiple assembly heads. This paper presents a hybrid genetic algorithm (HGA) to optimize the sequence of component placements and the arrangement of component types to feeders simultaneously for a chip shooter machine, that is, the component scheduling problem. The objective of the problem is to minimize the total assembly time. The GA developed in the paper hybridizes different search heuristics including the nearest-neighbor heuristic, the 2-opt heuristic, and an iterated swap procedure, which is a new improved heuristic. Compared with the results obtained by other researchers, the performance of the HGA is superior in terms of the assembly time. Scope and purpose When assembling the surface mount components on a PCB, it is necessary to obtain the optimal sequence of component placements and the best arrangement of component types to feeders simultaneously in order to minimize the total assembly time. Since it is very difficult to obtain the optimality, a GA hybridized with several search heuristics is developed. The type of machines being studied is the chip shooter machine. This paper compares the algorithm with a simple GA. It shows that the performance of the algorithm is superior to that of the simple GA in terms of the total assembly time.

A genetic algorithm approach to optimising component placement and retrieval sequence for chip shooter machines

A chip shooter machine in printed circuit board (PCB) assembly has three movable mechanisms: an X-Y table carrying a PCB, a feeder carrier with several feeders holding components and a rotary turret with multiple assembly heads to pick up and place components. In order to get the minimal placement or assembly time for a PCB on the machine, all the components on the board should be placed in a perfect sequence, and the components should be set up on a right feeder, or feeders since two feeders can hold the same type of components, and additionally, the assembly head should retrieve or pick up a component from a right feeder. The entire problem is very complicated, and this paper presents a genetic algorithm approach to tackle it.

A genetic algorithm to optimise the component placement process in the PCB assembly

In printed circuit board (PCB) assembly, the efficiency of the component placement process is dependent on two interrelated issues: the sequence of component placement, that is, the component sequencing problem, and the assignment of component types to feeders of the placement machine, that is, the feeder arrangement problem. In cases where some components with the same type are assigned to more than one feeder, the component retrieval problem should also be considered. Due to their inseparable relationship, a hybrid genetic algorithm is adopted to solve these three problems simultaneously for a type of PCB placement machines called the sequential pick-and-place (PAP) machine in this paper. The objective is to minimise the total distance travelled by the placement head for assembling all components on a PCB. Besides, the algorithm is compared with the methods proposed by other researchers in order to examine its effectiveness and efficiency.

A hybrid genetic algorithm for component sequencing and feeder arrangement

This paper presents a hybrid genetic algorithm to optimize the sequence of component placements on a printed circuit board and the arrangement of component types to feeders simultaneously for a pick-and-place machine with multiple stationary feeders, a fixed board table and a movable placement head. The objective of the problem is to minimize the total travelling distance, or the travelling time, of the placement head. The genetic algorithm developed in the paper hybrisizes different search heuristics including the nearest neighbor heuristic, the 2-opt heuristic, and an iterated swap procedure, which is a new improving heuristic. Compared with the results obtained by other researchers, the performance of the hybrid genetic algorithm is superior to others in terms of the distance travelled by the placement head.

The design and engineering of a reactor test facility for thermal processing of biomass

This thesis describes the design and engineering of a pressurised biomass gasification test facility. A detailed examination of the major elements within the plant has been undertaken in relation to specification of equipment, evaluation of options and final construction. The retrospective project assessment was developed from consideration of relevant literature and theoretical principles. The literature review includes a discussion on legislation and applicable design codes. From this analysis, each of the necessary equipment units was reviewed and important design decisions and procedures highlighted and explored. Particular emphasis was placed on examination of the stringent demands of the ASME VIII design codes. The inter-relationship of functional units was investigated and areas of deficiency, such as biomass feeders and gas cleaning, have been commented upon. Finally, plant costing was summarized in relation to the plant design and proposed experimental programme. The main conclusion drawn from the study is that pressurised gasification of biomass is far more difficult and expensive to support than atmospheric gasification. A number of recommendations have been made regarding future work in this area.

Aspects of the feeding behaviour of intensively reared trout

Feeding behaviour of trained rainbow trout was investigated by the use of demand feeders, under different light conditions. The effects of the energy content of diet, and the size, colour and texture of feed pellets, on the feeding behaviour, were studied. An attempt was made to locate the assumed centres for feeding and satiety in the hypothalamus of brain by the intraperitoneal injections of goldthioglucose. Feeding under nine different constant photoperiods at 160 lux, at a temperature of 13.5°C, showed that trout exhibit a rhythmic pattern of feeding behaviour in all photoperiods except in continuous darkness.Feeding rhythms of trout attributable to the degree of gut distension were formed every eight to ten hours. Further studies by varying levels of light intensity revealed the interaction of light intensity and photoperiod. At shorter photoperiods lower levels of light intensity decreased the feeding activity in terms of food intake but by increasing the photoperiod the same feeding activity was accomplished as by the fish subject to a short photoperiod but under higher light intensity.Simulated effect of increasing and decreasing daylengths did not affect the overall food intake and growth performance. Trout are quite efficient in adjusting their food intake in terms of energy content. Colour, size and texture of feed pellets affect the feeding responses and elicit preferential food selection behaviour in trout. Goldthioglucose induced some reversable toxic effects upon general physiology of trout and did not produce any lesions in the assumed areas of feeding and satiety centres in the brain.  It was concluded that the feeding behaviour of trout exhibited selective preferences according to the physical nature of food items and those preferences could be further influenced by the biotic and abiotic factors, light being one of the most important abiotic factors.

Meshing radial networks at 11kV

This project evaluates the benefits of meshing existing 11kV radial networks in order to reduce losses and maximise the connection of low carbon distributed generation. These networks are often arranged as radial feeders with normally-open links between two of the feeders; the link is closed only to enable continuity of supply to an isolated portion of a feeder following a fault on the network. However, this link could also be closed permanently thus operating the network as a meshed topology under non-faulted conditions. The study will look at loss savings and the addition of distributed generation on a typical network under three different scenarios; traditional radial feeders, fixed meshed network and a dynamic meshed network. The networks are compared in terms of feeder losses, capacity, voltage regulation and fault levels.

Connection design without accurate LV feeder load data:an argument for LV monitoring

Since privatisation, maintenance of DNO LV feeder maximum demand information has gradually demised in some Utility Areas, and it is postulated that lack of knowledge about 11kV and LV electrical networks is resulting in a less economical and energy efficient Network as a whole. In an attempt to quantify the negative impact, this paper examines ten postulated new connection scenarios for a set of real LV load readings, in order to find the difference in design solutions when LV load readings were and were not known. The load profiles of the substations were examined in order to explore the utilisation profile. It was found that in 70% of the scenarios explored, significant cost differences were found. These cost differences varied by an average of 1000%, between schemes designed with and without load readings. Obviously, over designing a system and therefore operating more, underutilised transformers becomes less financially beneficial and less energy efficient. The paper concludes that new connection design is improved in terms of cost when carried out based on known LV load information and enhances the case for regular maximum feeder demand information and/or metering of LV feeders. © 2013 IEEE.

Impacts of distributed generation on low-voltage distribution network protection

This paper reports work of a MEng student final year project, which looks in detail at the impacts that distributed generation can have on existing low-voltage distribution network protection systems. After a review of up-to-date protection issues, this paper will investigate several key issues that face distributed generation connections when it comes to network protection systems. These issues include, the blinding of protection systems, failure to automatically reclose, unintentional islanding, loss of mains power and the false tripping of feeders. Each of these problems impacts on protection systems in its own way. This study aims to review and investigate these problems via simulation demonstrations on one representative network to recommend solutions to practices.