Development and evaluation of a novel intranasal spray for the delivery of amantadine

The aim of this study was to develop and characterize an intranasal delivery system for amantadine hydrochloride (AMT). Optimal formulations consisted of a thermosensitive polymer Pluronic® 127 and either carboxymethyl cellulose or chitosan which demonstrated gel transition at nasal cavity temperatures (34 ± 1°C). Rheologically, the loss tangent (Tan δ) confirmed a 3-stage gelation phenomena at 34 ± 1°C and non-Newtonian behavior. Storage of optimized formulation carboxymethyl cellulose and optimal formulation chitosan at 4°C for 8 weeks resulted in repeatable release profiles at 34°C when sampled, with a Fickian mechanism earlier on but moving toward anomalous transport by week 8. Polymers (Pluronic® 127, carboxymethyl cellulose, and chitosan) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 ± 0.05 mM). Optimized formulation carboxymethyl cellulose and optimal formulation chitosan demonstrated slower release across an in vitro human nasal airway model (43%-44% vs 79 ± 4.58% for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated on nozzle insertion (5 mm), whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity.

Multiphase modelling of the characteristics of close coupled gas atomization

Not withstanding the high demand of metal powder for automotive and High Tech applications, there are still many unclear aspects of the production process. Only recentlyhas supercomputer performance made possible numerical investigation of such phenomena. This thesis focuses on the modelling aspects of primary and secondary atomization. Initially two-dimensional analysis is carried out to investigate the influence of flow parameters (reservoir pressure and gas temperature principally) and nozzle geometry on final powder yielding. Among the different types, close coupled atomizers have the best performance in terms of cost and narrow size distribution. An isentropic contoured nozzle is introduced to minimize the gas flow losses through shock cells: the results demonstrate that it outperformed the standard converging-diverging slit nozzle. Furthermore the utilization of hot gas gave a promising outcome: the powder size distribution is narrowed and the gas consumption reduced. In the second part of the thesis, the interaction of liquid metal and high speed gas near the feeding tube exit was studied. Both axisymmetric andnon-axisymmetric geometries were simulated using a 3D approach. The filming mechanism was detected only for very small metal flow rates (typically obtained in laboratory scale atomizers). When the melt flow increased, the liquid core overtook the adverse gas flow and entered in the high speed wake directly: in this case the disruption isdriven by sinusoidal surface waves. The process is characterized by fluctuating values of liquid volumes entering the domain that are monitored only as a time average rate: it is far from industrial robustness and capability concept. The non-axisymmetric geometry promoted the splitting of the initial stream into four cores, smaller in diameter and easier to atomize. Finally a new atomization design based on the lesson learned from previous cases simulation is presented.

Continous annular chromatography for the separation of carbohydrate mixtures

The continuous separation of beet molasses resulting in a sucrose rich product and a non-sugar waste product was carried out using a rotating annular chromatograph. The annulus was 12 mm wide and 1.4 m long and was packed with a sodium charged 5.5% cross-linked polystyrene ion exchange resin. Separation was achieved by the simultaneous mechanisms of ion exclusion, size exclusion and partition chromatography. The entire packed bed was slowly rotated while beet molasses was fed continuously through a stationary feed nozzle to the top of the bed. Each molasses constituent having a different relative affinity for the packing and the deionised water mobile phase describes a characteristic helical path as it progresses from the stationary feed point to the bottom of the rotating bed. Each solute then elutes from the annulus at a different angular distance from the feed and separation of the multicomponent mixture is thereby achieved. When a 35% w/w sucrose beet molasses feed was used the throughput achievable was 45.1 kg sucrose m~3 resin h"1. In addition to beet molasses separation other carbohydrate mixtures were separated. In particular the separation of glucose and fructose by Ligand exchange chromatography on a calcium charged ion exchange bed was carried out. The effects of flowrates, concentration, rotation rate, temperature and particle size on resolution and dilution of constituents in the mixtures to be separated were studied. A small test rig was designed and built to determine the cause of liquid maldistribution around the annulus. The problem was caused by the porous bed support media becoming clogged with fines being introduced by eluent flows and off the resin. An outer ring was constructed to house the bed support which could be quickly replaced with the onset of maldistribution. The computer simulation of the operation of the rotating annular chromatograph has been carried out successfully.

The atomisation of detergent slurries

A study was made to determine the conditions under which the optimum droplet size distribution (ie., narrowest size range with a minimum of fines and over-sized agglomerates), is generated in sprays from centrifugal pressure nozzles. A range of non-Newtonian detergent slurries were tested but the results are of wider application and parallel work was undertaken with water, ionic solutions and chalk slurries. Six centrifugal pressure nozzles were used and the drop-size distributions correlated as a function of fluid properties, pressure, fiowrate, feed temperature, and nozzle characteristics. Measurements were made using a Malvern Particle Size Anayser slung across a specially-designed transparent tower section of approximately 1.2m diameter in order to reduce obscuration caused by the spray and improve existing droplet sizing techniques. The results obtained were based upon the Rosin-Rammler distribution model and the Size Analyser provided a direct print-out of size distribution and the parameters characterising it. A Spraying System nozzle, AAASSTC8-8, produced the optimum spray distribution with the detergent slurry at a temperature of 60°C whilst operating at 1200 psi. With other fluids the Delevan 2.2SJ nozzle produced the optimum spray distribution operating at 1200 psi but with the Spraying Systems nozzles there was no clear-cut optimum set of conditions, ie. the nozzle and pressure varied depending upon the fluid being sprayed. The mechanisms of liquid sheet break-up and droplet dispersion were investigated in specially-constructed, scaled-up, transparent nozzles. A mathematical model of centrifugal pressure nozzle atomisation was developed based upon fundamental operating parameters rather than resorting to empirical correlations. This enabled theoretical predictions to be made over a wide range of operating conditions and nozzle types. The model predictions for volumetric fiowrate, liquid sheet length and air core diameter showed good agreement with the experimentally determined results. However, the model predicted smaller droplet sizes than were produced experimentally due to inaccuracies identified in the initial assumptions.

Mechanisms of drying of skin forming materials

The literature relating to evaporation from single droplets of pure liquids, and to the drying of droplets containing solids and of droplet sprays has been reviewed. The heat and mass transfer rates for a single droplet suspended from a nozzle were studied within a 42mm I.D. horizontal wind tunnel designed to supply hot dry air, to simulate conditions encountered in a practical spray dryer. A novel rotating glass nozzle was developed to facilitate direct measurements of droplet weight and core temperature. This design minimised heat conduction through the nozzle. Revised correlations were obtained for heat and mass transfer coefficients, for evaporation from pure water droplets suspended from a rotating nozzle. Nu = 2.0 + 0.27 (l/B)°-18Re°-5Pr°-83 Sh = 2.0 + 0.575 ((T0-T.)/Tomfc) -o.o4Reo.5 ^0.33 Experimental drying studies were carried out on single droplets of different types of skin-forming materials, namely, custard, gelatin, skim milk and fructose at air temperatures ranging from 19°C to 198°C. Dried crusts were recovered and examined by Scanning Electron Microscopy. Skin-forming materials were classified into three types according to the mechanisms of skin formation. In the first type (typified by droplets of custard and starch) skin formed due to gelatinisation at high temperatures. Increasing the drying temperature resulted in increased crust resistance to mass transfer due to increased granule swelling and the crust resistance was completely transferred to a skin resistance at drying temperatures > 150°C. In the second type e.g. gelatin droplets the skin formed immediately drying had taken place at any drying temperature. At drying temperature > 60° C a more resistant skin was formed. In the third type (typified by droplets of skim milk and fructose) the skin appeared on the droplet surface at a certain stage of the drying process under any drying conditions. As the drying temperature was increased the resistance of the skin to mass transfer increased. The drying rate history of any material depended upon the nature of the skin formed which, in turn, depended upon the drying conditions. A mathematical model was proposed for the drying of the first type of skin-forming material. This was based on the assumption that, once all the granules gelatinised at the gelatinisation temperature, a skin appeared instantaneously on the droplet surface. The experimentally-observed times at which the skin appeared on the droplets surfaces were in excellent agreement with those predicted from the model. The work should assist in understanding the fundamentals of paniculate drying processes, particularly when skin-formation occurs and may be a crucial factor in volatiles retention.

The hydrodynamic behaviour and mass transfer characteristics of single droplets in a pulsed sieve plate column

The literature relating to the performance of pulsed sieve plate liquid-liquid extraction columns and the relevant hydrodynamic phenomenon have been surveyed. Hydrodynamic behaviour and mass transfer characteristics of droplets in turbulent and non-turbulent conditions have also been reviewed. Hydrodynamic behaviour, i.e. terminal and characteristic velocity of droplets, droplet size and droplet breakup processes, and mass transfer characteristics of single droplets (d≤0.6 cm) were investigated under pulsed (mixer-settler & transitional regimes) and non-pulsed conditions in a 5.0 cm diameter, 100 cm high, pulsed sieve plate column with three different sieve plate types and variable plate spacing. The system used was toluene (displaced) - acetone - distilled water. Existing photographic techniques for following and recording the droplet behaviour, and for observing the parameters of the pulse and the pulse shape were further developed and improved. A unique illumination technique was developed by which a moving droplet could be photographed using cine or video photography with good contrast without using any dye. Droplet size from a given nozzle and droplet velocity for a given droplet diameter are reduced under pulsing condition, and it was noted that this effect is enhanced in the presence of sieve plate. The droplet breakup processes are well explained by reference to an impact-breakup mechanism. New correlations to predict droplet diameter based on this mechanism are given below.vskip 1.0cm or in dimensionless groups as follows:- (We)crit= 3.12 - 1.79 (Eo)crit A correlation based on the isotropic turbulence theory was developed to calculate droplet diameter in the emulsion regime.vskip 1.0cm Experimental results show that in the mixer-settler and transitional regimes, pulsing parameters had little effect on the overall dispersed phase mass transfer coefficient during the droplet formation and unhindered travel periods.

Gasification of rubberwood in a downdraft gasifier

The objectives of this research were to investigate the perforamnce of a rubberwood gasifier and engine with electricity generation and to identify opportunities for the implementation of such a system in Malaysia. The experimental work included the design, fabrication and commissioning of a throated downdraft gasifier in Malaysia. The gasifier was subsequently used to investigate the effect of moisture content, dry wood capacity and particle size of rubberwood on gasifier performance. Additional experiments were also conducted to investigate the influence of two different nozzle numbers and two different throat diameters on tar cracking. A total of 101 runs were completed during the duration of the research. From the experimental data, the average mass balance was found to be 92.65%. The average energy balance over the gasifier to hot raw gas was 98.7%, to cold clean gas was 102.4% and over the complete system was 101.9%. The heat loss from the gasifier was estimated to range from 10-26% of the chemical energy of the feedstock. From the downstream operation, the heat loss was estimated to range from 17-37% of the chemical energy of rubberwood feedstock. The maximum throughput for stable operation was found to be 60-70% of the maximum dry wood capacity. The gasifier was found to have a maximum turndown ratio of 5:1. It is also postulated that the phenomenon of turndown of the gasifier is due to a `bubble theory' occurring at the gasification zone, and this hypothesis is explained. For stable power output, the working range of the engine was found to be 5-33.5 kWe. The thermal efficiency and diesel displacement of the engine was found to be 17-18% and 65-70% respectively. The research also showed that rubberwood gasification in Malaysia is feasible if the price of diesel is above MR35/l and the price of wood is below MR120/tonne.

A study on the flow characteristics of an industrial radiant tube burner

The thesis presents an experimentally validated modelling study of the flow of combustion air in an industrial radiant tube burner (RTB). The RTB is used typically in industrial heat treating furnaces. The work has been initiated because of the need for improvements in burner lifetime and performance which are related to the fluid mechanics of the com busting flow, and a fundamental understanding of this is therefore necessary. To achieve this, a detailed three-dimensional Computational Fluid Dynamics (CFD) model has been used, validated with experimental air flow, temperature and flue gas measurements. Initially, the work programme is presented and the theory behind RTB design and operation in addition to the theory behind swirling flows and methane combustion. NOx reduction techniques are discussed and numerical modelling of combusting flows is detailed in this section. The importance of turbulence, radiation and combustion modelling is highlighted, as well as the numerical schemes that incorporate discretization, finite volume theory and convergence. The study first focuses on the combustion air flow and its delivery to the combustion zone. An isothermal computational model was developed to allow the examination of the flow characteristics as it enters the burner and progresses through the various sections prior to the discharge face in the combustion area. Important features identified include the air recuperator swirler coil, the step ring, the primary/secondary air splitting flame tube and the fuel nozzle. It was revealed that the effectiveness of the air recuperator swirler is significantly compromised by the need for a generous assembly tolerance. Also, there is a substantial circumferential flow maldistribution introduced by the swirier, but that this is effectively removed by the positioning of a ring constriction in the downstream passage. Computations using the k-ε turbulence model show good agreement with experimentally measured velocity profiles in the combustion zone and proved the use of the modelling strategy prior to the combustion study. Reasonable mesh independence was obtained with 200,000 nodes. Agreement was poorer with the RNG  k-ε and Reynolds Stress models. The study continues to address the combustion process itself and the heat transfer process internal to the RTB. A series of combustion and radiation model configurations were developed and the optimum combination of the Eddy Dissipation (ED) combustion model and the Discrete Transfer (DT) radiation model was used successfully to validate a burner experimental test. The previously cold flow validated k-ε turbulence model was used and reasonable mesh independence was obtained with 300,000 nodes. The combination showed good agreement with temperature measurements in the inner and outer walls of the burner, as well as with flue gas composition measured at the exhaust. The inner tube wall temperature predictions validated the experimental measurements in the largest portion of the thermocouple locations, highlighting a small flame bias to one side, although the model slightly over predicts the temperatures towards the downstream end of the inner tube. NOx emissions were initially over predicted, however, the use of a combustion flame temperature limiting subroutine allowed convergence to the experimental value of 451 ppmv. With the validated model, the effectiveness of certain RTB features identified previously is analysed, and an analysis of the energy transfers throughout the burner is presented, to identify the dominant mechanisms in each region. The optimum turbulence-combustion-radiation model selection was then the baseline for further model development. One of these models, an eccentrically positioned flame tube model highlights the failure mode of the RTB during long term operation. Other models were developed to address NOx reduction and improvement of the flame profile in the burner combustion zone. These included a modified fuel nozzle design, with 12 circular section fuel ports, which demonstrates a longer and more symmetric flame, although with limited success in NOx reduction. In addition, a zero bypass swirler coil model was developed that highlights the effect of the stronger swirling combustion flow. A reduced diameter and a 20 mm forward displaced flame tube model shows limited success in NOx reduction; although the latter demonstrated improvements in the discharge face heat distribution and improvements in the flame symmetry. Finally, Flue Gas Recirculation (FGR) modelling attempts indicate the difficulty of the application of this NOx reduction technique in the Wellman RTB. Recommendations for further work are made that include design mitigations for the fuel nozzle and further burner modelling is suggested to improve computational validation. The introduction of fuel staging is proposed, as well as a modification in the inner tube to enhance the effect of FGR.

Flowback of solids through distribution plates of gas fluidized beds and associated phenomena

This work is concerned with a study of certain phenomena related to the performance and design of distributors in gas fluidized beds with particular regard to flowback of solid particles. The work to be described is divided into two parts. I. In Part one, a review of published material pertaining to distribution plates, including details from the patent specifications, has been prepared. After a chapter on the determination of the incipient fluidizing velocity, the following aspects of multi-orifice distributor plates in gas fluidized beds have been studied: (i) The effect of the distributor on bubble formation related to the way in which even distribution of bubbles on the top surface of the fluidized bed is obtained, e.g. the desirable pressure drop ratio ?PD/?PB for the even distribution of gas across the bed. Ratios of distributor pressure drop ?PD to bed pressure drop at which stable fluidization occurs show reasonable agreement with industrial practice. There is evidence that larger diameter beds tend to be less stable than smaller diameter beds when these are operated with shallow beds. Experiments show that in the presence of the bed the distributor pressure drop is reduced relative to the pressure drop without the bed, and this pressure drop in the former condition is regarded as the appropriate parameter for the design of the distributor. (ii) Experimental measurements of bubble distribution at the surface has been used to indicate maldistribution within the bed. Maldistribution is more likely at low gas flow rates and with distributors having large fractional free area characteristics (i.e. with distributors having low pressure drops). Bubble sizes obtained from this study, as well as those of others, have been successfully correlated. The correlation produced implies the existence of a bubble at the surface of an orifice and its growth by the addition of excess gas from the fluidized bed. (iii) For a given solid system, the amount of defluidized particles stagnating on the distributor plate is influenced by the orifice spacing, bed diameter and gas flow rate, but independent of the initial bed height and the way the orifices are arranged on the distributor plate. II. In Part two, solids flowback through single and multi-orifice distributors in two-dimensional and cylindrical beds of solids fluidized with air has been investigated. Distributors equipped with long cylindrical nozzles have also been included in the study. An equation for the prediction of free flowback of solids through multi-orifice distributors has been derived. Under fluidized conditions two regimes of flowback have been differentiated, namely Jumping and weeping. Data in the weeping regime have been successfully correlated. The limiting gas velocity through the distributor orifices at which flowback is completely excluded is found to be indepnndent of bed height, but a function of distributor design and physical properties of gas and solid used. A criterion for the prediction of this velocity has been established. The decisive advantage of increasing the distributor thickness or using nozzles to minimize solids flowback in fluidized beds has been observed and the opportunity taken to explore this poorly studied subject area. It has been noted, probably for the first time, that with long nozzles, there exists a critical nozzle length above which uncontrollable downflow of solids occurs. A theoretical model for predicting the critical length of a bundle of nozzles in terms of gas velocity through the nozzles has been set up. Theoretical calculations compared favourably with experiments.

Spray drier simulation and air flow pattern studies

The literature pertaining to the key stages of spray drying has been reviewed in the context of the mathematical modelling of drier performance. A critical review is also presented of previous spray drying models. A new mathematical model has been developed for prediction of spray drier performance. This is applicable to slurries of rigid, porous crust-forming materials to predict trajectories and drying profiles for droplets with a distribution of sizes sprayed from a centrifugal pressure nozzle. The model has been validated by comparing model predictions to experimental data from a pilot-scale counter-current drier and from a full-scale co-current drier. For the latter, the computed product moisture content was within 2%, and the computed air exit temperature within 10oC of experimental data. Air flow patterns have been investigated in a 1.2m diameter transparent countercurrent spray tower by flow visualisation. Smoke was introduced into various zones within the tower to trace the direction, and gauge the intensity, of the air flow. By means of a set of variable-angle air inlet nozzles, a variety of air entry configurations was investigated. The existence of a core of high rotational and axial velocity channelling up the axis of the tower was confirmed. The stability of flow within the core was found to be strongly dependent upon the air entry arrangement. A probe was developed for the measurement of air temperature and humidity profiles. This was employed for studying evaporation of pure water drops in a 1.2m diameter pilot-scale counter-current drier. A rapid approach to the exit air properties was detected within a 1m distance from the air entry ports. Measured radial profiles were found to be virtually flat but, from the axial profiles, the existence of plug-flow, well-mixed-flow and some degree of air short-circuiting can be inferred. The model and conclusions should assist in the improved design and optimum operation of industrial spray driers.

Influence of impact angles on penetration rates of CRAs exposed to a high velocity multiphase flow

A combined flow loop - jet impingement pilot plant has been used to determine mass loss rates in a mixed gas - saltwater - sand multiphase flow at impact velocities up to 70 m/s. Artificial brine with a salt content of 27 g/1 was used as liquid phase. Sand content, with grain size below 150 µ, was 2.7 g/l brine. CO at a pressure of 15 bar was used as gas phase. The impact angle between jet stream (nozzle) and sample surface was varied between 30 and 90°. Rectangular stainless steel disc samples with a size of 20 × 15 × 5 mm were used. They were mechanically ground and polished prior to testing. Damaged surfaces of specimens exposed to the high velocity multiphase flow were investigated by stereo microscopy, scanning electron microscopy (SEM) and an optical device for 3D surface measurements. Furthermore, samples were investigated by applying atomic force microscopy (AFM), magnetic force microscopy (MFM) and nanoindentation. Influence of impact velocity and impact angle on penetration rates (mass loss rates) of two CRAs (UNS S30400 and N08028) are presented. Moreover effects of chemical composition and mechanical properties are critically discussed. © 2008 by NACE International.

Lubrication efficiency and die design in wire drawing

With the competitive challenge facing business today, the need to keep cost down and quality up is a matter of survival. One way in which wire manufacturers can meet this challenge is to possess a thorough understanding of deformation, friction and lubrication during the wire drawing process, and therefore to make good decisions regarding the selection and application of lubricants as well as the die design. Friction, lubrication and die design during wire drawing thus become the subject of this study. Although theoretical and experimental investigations have been being carried out ever since the establishment of wire drawing technology, many problems remain unsolved. It is therefore necessary to conduct further research on traditional and fundamental subjects such as the mechanics of deformation, friction, lubrication and die design in wire drawing. Drawing experiments were carried out on an existing bull-block under different cross-sectional area reductions, different speeds and different lubricants. The instrumentation to measure drawing load and drawing speed was set up and connected to the wire drawing machine, together with a data acquisition system. A die box connected to the existing die holder for using dry soap lubricant was designed and tested. The experimental results in terms of drawing stress vs percentage area reduction curves under different drawing conditions were analysed and compared. The effects on drawing stress of friction, lubrication, drawing speed and pressure die nozzle are discussed. In order to determine the flow stress of the material during deformation, tensile tests were performed on an Instron universal test machine, using the wires drawn under different area reductions. A polynomial function is used to correlate the flow stress of the material with the plastic strain, on which a general computer program has been written to find out the coefficients of the stress-strain function. The residual lubricant film on the steel wire after drawing was examined both radially and longitudinally using an SEM and optical microscope. The lubricant film on the drawn wire was clearly observed. Therefore, the micro-analysis by SEM provides a way of friction and lubrication assessment in wire drawing.

Time scale analysis for fluidized bed melt granulation I: granule-granule and granule-droplet collision rates

Fluidized bed spray granulators (FBMG) are widely used in the process industry for particle size growth; a desirable feature in many products, such as granulated food and medical tablets. In this paper, the first in a series of four discussing the rate of various microscopic events occurring in FBMG, theoretical analysis coupled with CFD simulations have been used to predict granule–granule and droplet–granule collision time scales. The granule–granule collision time scale was derived from principles of kinetic theory of granular flow (KTGF). For the droplet–granule collisions, two limiting models were derived; one is for the case of fast droplet velocity, where the granule velocity is considerable lower than that of the droplet (ballistic model) and another for the case where the droplet is traveling with a velocity similar to the velocity of the granules. The hydrodynamic parameters used in the solution of the above models were obtained from the CFD predictions for a typical spray fluidized bed system. The granule–granule collision rate within an identified spray zone was found to fall approximately within the range of 10-2–10-3 s, while the droplet–granule collision was found to be much faster, however, slowing rapidly (exponentially) when moving away from the spray nozzle tip. Such information, together with the time scale analysis of droplet solidification and spreading, discussed in part II and III of this study, are useful for probability analysis of the various event occurring during a granulation process, which then lead to be better qualitative and, in part IV, quantitative prediction of the aggregation rate.