Formulation and Assessment of Taste-masked Electrospun Fibre Mats for Paediatric Drug Delivery

Since the Paediatric Regulation came into force by the European Medicines Agency in 2007, the drive to formulate age-appropriate dosage forms has been accelerated. The aim of this thesis was to develop new approaches for paediatric formulation design through the optimisation of novel taste-masking and taste-assessment methods. Electrospinning was demonstrated to be a suitable taste-masking technology, producing fibre mats that can be further formulated into easy to swallow oral films. The electrospinning of Eudragit E PO, a taste-masking polymer, was optimised using Quality by Design principles and in particular Design of Experiment. To further enhance the taste-masking capability of the electrospun mat, co-axial electrospinning was utilised using another taste-masking polymer, Kollicoat Smartseal. The use of both polymers successfully taste-masked chlorpheniramine maleate, a known bitter anti-histamine. This was demonstrated using an electronic biosensor tasting system or E-tongue. The E-tongue was used to assess the bitterness threshold of this model drug but also of other standard bitter drugs for benchmarking. In addition, it was used to taste-assess various formulations which aided in ranking and deselecting formulations. Electrospun fibre mats can be further processed into a number of different dosage forms for final presentation to the patient. The fibre mats were designed to be presented as an oral film. A water-soluble outer layer was added to the films using multi-axial electrospinning. A human panel was conducted to investigate the mouthfeel and overall acceptability of electrospun PVA films versus solvent-cast PVA films. The electrospun films were found to be as acceptable as the standard solvent-cast films, a very promising result for clinical translation. PVA and PVP were electrospun with the previously optimised polymers using tri-axial and tetra-axial electrospinning. The taste of the multi-axial electrospun fibre mats were assessed and it was found that adding a water-soluble outer layer reduces the taste-masking ability. Thus, it was found that electrospinning of a bitter drug using hydrophobic taste-masking polymers is very promising in the formulation of paediatric oral films

Suspension Near-Field Electrospinning: a Nanofabrication Method of Polymer Nanoarray Architectures for Tissue Engineering

Chapter 1. This chapter is divided into six sections. The first will discuss the issue of nerve tissue loss, and the strategies of therapy (1.1). The second describes the role of nanofabrication in tissue engineering (1.2). The third section details the theoretical background of electrospinning in terms of solution and process parameters (1.3). The fourth section introduces near-field electrospinning (NFES), recent advances in this field and the principles of NFES techniques (1.4). The fifth section details objectives for a tissue engineered construct for neural cell therapy, and presents possible viable solutions (1.5). The sixth summarizes the aims and structure of this thesis (1.6)..

Air movement and energy flows in an air-conditioned and partitioned industrial environment.

This study concerns an investigation into air movement and associated energy flows within the environment of a synthetic fibre producing factory. A multiplicity of airconditioning and ventilation systems were operated within the factory to provide a suitable atmosphere for the yarn, and also to allow some degree of comfort in hot production areas. Potential for improved operation of these systems was anticipated. Initial experiments showed certain anomalies and problems relating to air conditions and air movement; and an important facet of the production areas was identified as the regular partitioning created by the machine layout. A review of previous studies of building air flows indicated a lack of information relating to industrial and partitioned areas. Mathematical relationships for air flows were studied and the interactions of similar, closely spaced partitions were considered. A series of model scale tests using simple layouts supported a theory of interaction. The effect was substantial for wall type partitions and a considerable overestimation could result from the simple additive approach to determination of total resistance.At the factory a computer based monitoring scheme was designed and installed in order to establish environmental conditions and energy flows. The concept of "total thermal efficiency" was developed as a means of evaluating the performance of some of the air-conditioning systems. Considerable variations were evident between seasons and between systems; improvements being possible and recommended. Air flows were also investigated using Nitrous Oxide as a tracer gas. The effect of the internal partitioning combined with the high degree of ventilation and air-conditioning was to "compartmentalize" the spaces between the machines in the production areas, semi-isolating each from its neighbours. Thus, the results of the simplified model scale work could not be applied directly. However the isolation of the spaces offers potential for better systems operation by reducing air-conditioning requirements

Factories of the Future

Engineering; Industrial engineering; Production engineerin

Development and characterisation of a membrane gradostat bioreactor for the bioremediation of aromatic pollutants using white rot fungi

Bioremediation of aromatic pollutants using the ligninolytic enzymes of the white rot fungi has been thoroughly researched and has been shown to have considerable potential for industrial application. However, little success in scale-up and industrialisation of this technology has been attained due to problems associated with the continuous production of the pollutant-degrading enzymes using conventional bioreactor systems. The low productivities reported result from the incompatibility of conventional submerged culture reactor techniques with the physiological requirements of these fungi which have evolved on a solid-air interface, viz. wood. The enzymes are also produced only during the stationary phase of growth and can therefore be regarded as secondary metabolites. This study reports the conceptualisation, characterisation and evaluation of a novel bioreactor system as a solution to the continuous production of idiophasic pollutant degrading enzymes by the white rot fungus Phanerochaete chlysosporium. The reactor concept evolved from observation of these fungi in their native state, i. e. the metabolism of lignocellulosic material and involves the immobilisation of the organism onto a capillary ultrafiltration membrane. Nutrient gradients established across the biofilm, an inherent characteristic of fixed bed perfusion reactors, are exploited to provide both nutrient rich and nutrient poor zones across the biofilm. This allows growth or primary metabolism in the nutrient rich zone, pushing older biomass into the nutrient poor zone where secondary metabolism is induced by nutrient starvation. In effect, this represents a transformation of the events of a batch culture from a temporal to a spatial domain, allowing continuous production of secondary metabolites over time. Direct contact of the outer part of the biofilm with an air stream simulated the solid-air interface of the native state of the fungus. In order to facilitate the practical application of the membrane gradostat reactor (MGR) concept, conventional capillary membranes and membrane bioreactor modules were first evaluated. These were found to be unsuitable for application of the MGR concept. However, critical analysis of the shortcomings of the conventional systems resulted in the formulation of a set of design criteria for the development of a suitable membrane and module. These design criteria were satisfied by the development of a novel capillary membrane for membrane bioreactors, as well as a transverse flow membrane module, which is a novel approach in membrane bioreactor configuration. For the physiological characterisation of the MGR concept, a single fibre bioreactor unit was designed, which allowed destructive sampling of the biofilm for analysis. Using this system, it was shown that distinct morphological zones could be observed radially across the mature biofilm obtained through MGR operation. That these morphotypes do represent the temporal events of a typical batch culture in a spatial domain was confirmed by following the morphological changes occurring during batch culture of the immobilised fungus where the onset of primary and secondary metabolic conditions were manipulated through control of the nutrient supply. The different morphotypes were correlated to distinct growth phases by comparison of the morphology to the secretion of known enzymatic markers for secondary metabolism, viz. succinate dehydrogenase and cytochrome C oxidoreductase. Detailed structure-function analysis of the biofilm using transmission electron microscopy and adapted enzyme cytochemical staining techniques showed that the biofilm appeared to operate as a co-ordinated unit, with primary and secondary metabolism apparently linked in one thallus through nutrient translocation. This study provided new insights into the physiology of P. chrysosp,o rium and a detailed descriptive model was formulated which correlates well to existing models of wood degradation by the white rot fungi (WRF). Evaluation of the process on a laboratory scale using a novel transverse flow membrane bioreactor showed that a volumetric productivity of 1916 U.L.⁻¹day⁻¹ for manganese peroxidase, one of the pollutant degrading enzymes, could be attained, corresponding to a final concentration of 2 361 U.L.⁻¹ This may be compared to the best reported system (Moreira el at. 1997), where a volumetric productivity of 202 U.L.⁻¹day⁻¹was achieved with a final concentration of 250 U.L.⁻¹ However, MGR productivity is yet to be subjected to rigorous optimisation studies. The process could be operated continuously for 60 days. However, peak productivity could not be maintained for long periods. This was found to be due to physical phenomena relating to the fluid dynamics of the system which caused fluid flow maldistribution, which would have to be resolved through engineering analysis. In evaluation of the MGR concept for aromatic pollutant removal, in this case ρ- cresol, from growth medium, good performance was also achieved. The VmaxKm calculated by linear regression for the MGR was 0.8 (R² = 0.93), which compared favourably to that reported by Lewandowski et al. (1990), who obtained a Vmax/Km of 0.34 for a packed bed reactor treating chlorophenol. It was concluded that the MGR showed suitable potential to warrant further development, and that the descriptive characterisation of the biofilm physiology provided a sufficient basis for process analysis once engineering aspects ofthe system could be resolved

Factories of the Future

Engineering; Industrial engineering; Production engineerin

Proceedings of the International Workshop on Medical Ultrasound Tomography: 1.- 3. Nov. 2017, Speyer, Germany

Ultrasound Tomography is an emerging technology for medical imaging that is quickly approaching its clinical utility. Research groups around the globe are engaged in research spanning from theory to practical applications. The International Workshop on Medical Ultrasound Tomography (1.-3. November 2017, Speyer, Germany) brought together scientists to exchange their knowledge and discuss new ideas and results in order to boost the research in Ultrasound Tomography