Ordered mixing of drugs with particulate excipients

A novel direct compression tableting excipient has been made by recrystallisation of lactose. The particles produced had high porosity, high specific surface area and high surface roughness. The resistance to segregation of ordered mixes formed between a model drug; potassium chloride and the excipients recrystallised lactose, spray crystallised maltose-dextrose (Emdexl and a direct compacting sugar (Dipac) was studied using a vibrational segregation model. The highly porous excipients, Emdex and recrystallised lactose formed ordered mixes which did not segregate even at high accelerations and low frequencies whereas the relatively smooth excipient, Dipac, displayed marked segregation in most vibration conditions. The vibrations were related to practical conditions measured in pharmaceutical process machinery. The time required to form an ordered mix was inversely related to the stability of the mix when subjected to vibration. An ultracentrifuge technique was developed to determine the interparticle adhesion forces holding drug and excipient particles together as ordered units. Excipient powders such as Emdex and recrystallised lactose, which formed non-segregating ordered mixes, had high interparticle adhesion forces. Other ordered mixes that segregated when subjected to different vibration conditions were found to have large quantities of weekly-bound drug particles; such mixes included those with Dipac as the carrier excipient as well as those containing a high concentration of drug. The electrostatic properties of different drug and excipient powders were studied using a Faraday well and an electrometer. Excipient powders such as Emdex and recrystallised lactose which formed stable ordered mixes also had a widely different surface charge in comparison with drug particles, whereas Dipac had a similar surface charge to the drug particles and formed unstable ordered mixes. A specially constructed triboelectric charging apparatus based on an air cyclone was developed to increase the affinity of drug particles for different excipient particles. Using triboelectrification to increase the interparticle adhesion forces, the segregation tendencies of unstable ordered mixes were greatly reduced. The stability of ordered mixes is shown to be related to both the surface physical characteristics and the surface electrical properties of the constituent carrier (excipientl particles.

Mixing the grant cocktail:towards an understanding of the outcomes of financial support to small firms

One of the key policy objectives of government at national and regional level, is to overcome the constraints preventing local industry achieving greater competitiveness in the international market-place. This paper examines the impact of grant assistance to Northern Ireland small firms delivered over the period 1994 ^ 97 by the former Local Enterprise Development Unit through its Growth Business Support Programme (GBSP). Previous work by the authors showed that there was some tentative evidence to suggest a link between employment growth and grant aid provided to very small firms (fewer than 10 employees) assisted under the GBSP. The central objective of the empirical work reported in this paper is to extend the previous analysis by understanding the extent to which the value of financial assistance influences growth (employment, turnover, and productivity measures) and if differential impacts arise depending on the nature and timing (lag structures) of the grant assistance.

Flow field analysis of some mixing and conveying screw element regions, within a closely intermeshing, co-rotating twin-screw extruder.

Grafting of antioxidants and other modifiers onto polymers by reactive extrusion, has been performed successfully by the Polymer Processing and Performance Group at Aston University. Traditionally the optimum conditions for the grafting process have been established within a Brabender internal mixer. Transfer of this batch process to a continuous processor, such as an extruder, has, typically, been empirical. To have more confidence in the success of direct transfer of the process requires knowledge of, and comparison between, residence times, mixing intensities, shear rates and flow regimes in the internal mixer and in the continuous processor.The continuous processor chosen for the current work in the closely intermeshing, co-rotating twin-screw extruder (CICo-TSE). CICo-TSEs contain screw elements that convey material with a self-wiping action and are widely used for polymer compounding and blending. Of the different mixing modules contained within the CICo-TSE, the trilobal elements, which impose intensive mixing, and the mixing discs, which impose extensive mixing, are of importance when establishing the intensity of mixing. In this thesis, the flow patterns within the various regions of the single-flighted conveying screw elements and within both the trilobal element and mixing disc zones of a Betol BTS40 CICo-TSE, have been modelled using the computational fluid dynamics package Polyflow. A major obstacle encountered when solving the flow problem within all of these sets of elements, arises from both the complex geometry and the time-dependent flow boundaries as the elements rotate about their fixed axes. Simulation of the time dependent boundaries was overcome by selecting a number of sequential 2D and 3D geometries, used to represent partial mixing cycles. The flow fields were simulated using the ideal rheological properties of polypropylene and characterised in terms of velocity vectors, shear stresses generated and a parameter known as the mixing efficiency. The majority of the large 3D simulations were performed on the Cray J90 supercomputer situated at the Rutherford-Appleton laboratories, with pre- and postprocessing operations achieved via a Silicon Graphics Indy workstation. A mechanical model was constructed consisting of various CICo-TSE elements rotating within a transparent outer barrel. A technique has been developed using coloured viscous clays whereby the flow patterns and mixing characteristics within the CICo-TSE may be visualised. In order to test and verify the simulated predictions, the patterns observed within the mechanical model were compared with the flow patterns predicted by the computational model. The flow patterns within the single-flighted conveying screw elements in particular, showed good agreement between the experimental and simulated results.

Investigation of chaotic mixing in laminar fluid systems by the use of computational fluid dynamics

This work presents significant development into chaotic mixing induced through periodic boundaries and twisting flows. Three-dimensional closed and throughput domains are shown to exhibit chaotic motion under both time periodic and time independent boundary motions, A property is developed originating from a signature of chaos, sensitive dependence to initial conditions, which successfully quantifies the degree of disorder withjn the mixing systems presented and enables comparisons of the disorder throughout ranges of operating parameters, This work omits physical experimental results but presents significant computational investigation into chaotic systems using commercial computational fluid dynamics techniques. Physical experiments with chaotic mixing systems are, by their very nature, difficult to extract information beyond the recognition that disorder does, does not of partially occurs. The initial aim of this work is to observe whether it is possible to accurately simulate previously published physical experimental results through using commercial CFD techniques. This is shown to be possible for simple two-dimensional systems with time periodic wall movements. From this, and subsequent macro and microscopic observations of flow regimes, a simple explanation is developed for how boundary operating parameters affect the system disorder. Consider the classic two-dimensional rectangular cavity with time periodic velocity of the upper and lower walls, causing two opposing streamline motions. The degree of disorder within the system is related to the magnitude of displacement of individual particles within these opposing streamlines. The rationale is then employed in this work to develop and investigate more complex three-dimensional mixing systems that exhibit throughputs and time independence and are therefore more realistic and a significant advance towards designing chaotic mixers for process industries. Domains inducing chaotic motion through twisting flows are also briefly considered. This work concludes by offering possible advancements to the property developed to quantify disorder and suggestions of domains and associated boundary conditions that are expected to produce chaotic mixing.

Solids mixing and segregation in a gas spout-fluid bed-effect of the distributor design

This work is concerned with the assessment of a newer version of the spout-fluid bed where the gas is supplied from a common plenum and the distributor controls the operational phenomenon. Thus the main body of the work deals with the effect of the distributor design on the mixing and segregation of solids in a spout-filled bed. The effect of distributor design in the conventional fluidised bed and of variation of the gas inlet diameter in a spouted bed were also briefly investigated for purpose of comparison. Large particles were selected for study because they are becoming increasingly important in industrial fluidised beds but have not been thoroughly investigated. The mean particle diameters of the fraction ranged from 550 to 2400 mm, and their specific gravity from 0.97 to 2.45. Only work carried out with binary systems is reported here. The effect of air velocity, particle properties, bed height, the relative amount of jetsam and flotsam and initial conditions on the steady-state concentration profiles were assessed with selected distributors. The work is divided into three sections. Sections I and II deal with the fluidised bed and spouted bed systems. Section III covers the development of the spout-filled bed and its behaviour with reference to distributor design and it is shown how benefits of both spouting and fluidising phenomena can be exploited. In the fluidisation zone, better mixing is achieved by distributors which produce a large initial bubble diameter. Some common features exist between the behaviour of unidensity jetsam-rich systems and different density flotsam-rich systems. The shape factor does not seem to have an affect as long as it is only restricted to the minor component. However, in the case of the major component, particle shape significantly affects the final results. Studies of aspect ratio showed that there is a maximum (1.5) above which slugging occurs and the effect of the distributor design is nullified. A mixing number was developed for unidensity spherical rich systems, which proved to be extremely useful in quantifying the variation in mixing and segregation with changes in distributor design.

Variable impedance bearings for large rotating machinery

This thesis describes an investigation which was carried out under the Interdisciplinary Higher Degres (IHD) Scheme of The University of Aston in Birmingham. The investigation, which involved joint collaboration between the IHD scheme, the Department of Mechanical Engineering, and G.E.C. Turbine Generators Limited, was concerned with hydrostatic bearing characteristics and of how hydrostatic bearings could be used to enable turbine generator rotor support impedances to be controlled to give an improved rotor dynamic response. Turbine generator rotor critical speeds are determined not only by the mass and flexibility of the rotor itself, which are relatively easily predicted, but also by the dynamic characteristics of the bearing oil film, pedestal, and foundations. It is because of the difficulty in accurately predicting the rotor support characteristics that the designer has a problem in ensuring that a rotor's normal running speed is not close to one of its critical speeds. The consequence of this situation is that some rotors do have critical speeds close to their normal running speed and the resulting high levels of vibration cause noise, high rotor stresses, and a shortening of bearing life. A combined theoretical and experimental investigation of the effects of mounting the normal rotor journal bearing in a hydrostatic bearing was carried out. The purpose of the work was to show that by changing the oil flow resistance offered by capillaries connecting accumulators to the hydrostatic bearing, the overall rotor support characteristics could be tuned to enable rotor critical speeds to be moved at will. Testing of a combined journal and hydrostatic bearing has confirmed the theory of its operation and a theoretical study of a full size machine showed that its critical speed could be moved by over 350 rpm and that its rotor vibration at running speed could be reduced by 80%.

The impact of NC machinery upon manufacturing industry

The changing face of industry due to the adoption of `New Technology' is briefly discussed, as are the corresponding structural changes in the workforce. The adoption of NC machinery is identified as one of the major innovations affecting the structure of industry. The development of NC machinery, and of relevant programming techniques are reviewed, and the problems arising from its initial sponsorship by the aerospace industry are highlighted. The process of its subsequent diffusion into industry is reviewed. Skill levels adopted for NC use in Britain and Germany are discussed, and analysed to create a structural pattern. These classifications of skill levels are then used to examine the organisational structures adopted by companies utilising NC machines. The greater use made of higher level shop floor skills by German companies is discussed. The results of two surveys of the use made of NC by companies in the North East of England are presented. Effective company organisation for NC use is described, and lack of foresight is shown to lead to vulnerability problems where skills can become concentrated in a few key people. This led to closure of a company in one instance. It is shown that small sub-contract companies have adopted a highly skilled shop floor workforce, and that they have survived in the present hostile economic environment, whilst companies who have used NC to de-skill the shop floor contracted dramatically in the same period. The lack of awareness of the potential for reviewing the product design in relation to the flexibility of NC, so leading to reductions in work in progress levels, is highlighted. Recommendations for skill structures appropriate to various sized companies and suitable training programs are presented to ensure that the full potential of NC machinery is achieved.

Flexible high speed machinery

The thesis describes an investigation into methods for the design of flexible high-speed product processing machinery, consisting of independent electromechanically actuated machine functions which operate under software coordination and control. An analysis is made of the elements of traditionally designed cam-actuated, mechanically coupled machinery, so that the operational functions and principal performance limitations of the separate machine elements may be identified. These are then used to define the requirements for independent actuators machinery, with a discussion of how this type of design approach is more suited to modern manufacturing trends. A distributed machine controller topology is developed which is a hybrid of hierarchical and pipeline control. An analysis is made, with the aid of dynamic simulation modelling, which confirms the suitability of the controller for flexible machinery control. The simulations include complex models of multiple independent actuators systems, which enable product flow and failure analyses to be performed. An analysis is made of high performance brushless d.c. servomotors and their suitability for actuating machine motions is assessed. Procedures are developed for the selection of brushless servomotors for intermittent machine motions. An experimental rig is described which has enabled the actuation and control methods developed to be implemented. With reference to this, an evaluation is made of the suitability of the machine design method and a discussion is given of the developments which are necessary for operational independent actuators machinery to be attained.

Investigation of two-wave mixing in arbitrary oriented sillenite crystals

A generalized systematic description of the Two-Wave Mixing (TWM) process in sillenite crystals allowing for arbitrary orientation of the grating vector is presented. An analytical expression for the TWM gain is obtained for the special case of plane waves in a thin crystal (|g|d«1) with large optical activity (|g|/?«1, g is the coupling constant, ? the rotatory power, d the crystal thickness). Using a two-dimensional formulation the scope of the nonlinear equations describing TWM can be extended to finite beams in arbitrary geometries and to any crystal parameters. Two promising applications of this formulation are proposed. The polarization dependence of the TWM gain is used for the flattening of Gaussian beam profiles without expanding them. The dependence of the TWM gain on the interaction length is used for the determination of the crystal orientation. Experiments carried out on Bi12GeO20 crystals of a non-standard cut are in good agreement with the results of modelling.

Resonant two-wave mixing in photorefractive materials with the aid of dc and ac fields

A recently predicted resonant effect for the enhancement of two-wave mixing in photorefractive materials is investigated. The resonance occurs when the frequency of the applied ac field agrees with the eigenfrequency of the excited space-charge wave. Experimentally a clear resonance is found, as predicted by the theory, for high dc electric fields, but the resonance is smeared out for lower fields. A modified theory, taking into account the second temporal harmonic of the space-charge wave, shows good agreement with the experimental results.