Amino acid-modified spray-dried powders with enhanced aerosolisation properties for pulmonary drug delivery

In this study, the amino acids arginine, aspartic acid, leucine, phenylalanine and threonine were investigated as 'dispersibility enhancers' in spray-dried powders for inhalation. Parameters such as spray-dried yield, tapped density, and Carr's Index were not predictive of aerosolisation performance. In addition, whilst the majority of amino acid-modified powders displayed suitable particle size distribution for pulmonary administration and potentially favourable low moisture content, in vitro particle deposition was only enhanced for the leucine-modified powder. In summary, leucine can be used to enhance the dispersibility and aerosolisation properties of spray-dried powders for pulmonary drug delivery. © 2007 Elsevier B.V. All rights reserved.

Further studies on flow distribution on distillation sieve trays

The thesis describes experimental work on the possibility of using deflection baffles in conventional distillation trays as flow straightening devices, with the view of enhancing tray efficiency. The mode of operation is based on deflecting part of the liquid momentum from the centre of the tray to the segment regions in order to drive stagnating liquid at the edges forward. The first part of the work was a detailed investigation into the two-phase flow patterns produced on a conventional sieve tray having 1 mm hole size perforations. The data provide a check on some earlier work and extend the range of the existing databank, particularly to conditions more typical of industrial operation. A critical survey of data collected on trays with different hole sizes (Hine, 1990; Chambers, 1993; Fenwick, 1996; this work) showed that the hole diameter has a significant influence on the flow regime, the size of the stagnant regions and the hydraulic and mass transfer performance. Five modified tray topologies were created with different configurations of baffles and tested extensively in the 2.44 m diameter air-water pilot distillation simulator for their efficacy in achieving uniform flow across the tray and for their impact on tray loading capacity and mass transfer efficiency. Special attention was given to the calibration of the over 100 temperature probes used in measuring the water temperature across the tray on which the heat and mass transfer analogy is based. In addition to normal tray capacity experiments, higher weir load experiments were conducted using a 'half-tray' mode in order to extend the range of data to conditions more typical of industrial operation. The modified trays show superior flow characteristics compared to the conventional tray in terms of the ability to replenish the zones of exceptionally low temperatures and high residence times at the edges of the tray, to lower the bulk liquid gradient and to achieve a more uniform flow across the tray. These superior flow abilities, however, tend to diminish with increasing weir load because of the increasing tendency for the liquid to jump over the barriers instead of flowing over them. The modified tray topologies showed no tendency to cause undue limitation to tray loading capacity. Although the improvement in the efficiency of a single tray over that of the conventional tray was moderate and in some cases marginal, the multiplier effect in a multiple tray column situation would be significant (Porter et al., 1972). These results are in good agreement with an associated CFD studies (Fischer, 1999) carried out by partners in the Advanced Studies in Distillation consortium. It is concluded that deflection baffles can be used in a conventional distillation sieve tray to achieve better liquid flow distribution and obtain enhanced mass transfer efficiency, without undermining the tray loading capacity. Unlike any other controlled-flow tray whose mechanical complexity impose stringent manufacturing and installation tolerances, the baffled-tray models are simple to design, manufacture and install and thus provide an economic method of retrofitting badly performing sieve trays both in terms of downtime and fabrication. NOTE APPENDICES 2-5 ARE ON A SEPARATE FLOPPY DISK ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY WITH PRIOR ARRANGEMENT

The separation of secondary oil-water dispersions in particulate beds

The literature relating to haze formation, methods of separation, coalescence mechanisms, and models by which droplets <100 μm are collected, coalesced and transferred, have been reviewed with particular reference to particulate bed coalescers. The separation of secondary oil-water dispersions was studied experimentally using packed beds of monosized glass ballotini particles. The variables investigated were superficial velocity, bed depth, particle size, and the phase ratio and drop size distribution of inlet secondary dispersion. A modified pump loop was used to generate secondary dispersions of toluene or Clairsol 350 in water with phase ratios between 0.5-6.0 v/v%.Inlet drop size distributions were determined using a Malvern Particle Size Analyser;effluent, coalesced droplets were sized by photography. Single phase flow pressure drop data were correlated by means of a Carman-Kozeny type equation. Correlations were obtained relating single and two phase pressure drops, as (ΔP2/μc)/ΔP1/μd) = kp Ua Lb dcc dpd Cine A flow equation was derived to correlate the two phase pressure drop data as, ΔP2/(ρcU2) = 8.64*107 [dc/D]-0.27 [L/D]0.71 [dp/D]-0.17 [NRe]1.5 [e1]-0.14 [Cin]0.26  In a comparison between functions to characterise the inlet drop size distributions a modification of the Weibull function provided the best fit of experimental data. The general mean drop diameter was correlated by: q_p q_p p_q /β      Γ ((q-3/β) +1) d qp = d fr  .α        Γ ((P-3/β +1 The measured and predicted mean inlet drop diameters agreed within ±15%. Secondary dispersion separation depends largely upon drop capture within a bed. A theoretical analysis of drop capture mechanisms in this work indicated that indirect interception and London-van der Waal's mechanisms predominate. Mathematical models of dispersed phase concentration m the bed were developed by considering drop motion to be analogous to molecular diffusion.The number of possible channels in a bed was predicted from a model in which the pores comprised randomly-interconnected passage-ways between adjacent packing elements and axial flow occured in cylinders on an equilateral triangular pitch. An expression was derived for length of service channels in a queuing system leading to the prediction of filter coefficients. The insight provided into the mechanisms of drop collection and travel, and the correlations of operating parameters, should assist design of industrial particulate bed coalescers.

Properties and performance of polymer modified cements and mortars

Polymer modified cements and mortars have become popular for use as patch repair materials. General evidence suggests that these materials offer considerable improvements compared to traditional mortars although the mechanisms for this are not fully understood. This work elucidates the factors which govern some properties and performance of different polymer systems. In view of the wide range of commercial systems available, investigations concentrated on the use of three of the most commonly available groups of polymers. These were: (1) Styrene Butadiene Rubber (SBR), (2) Acrylics and, (3) Ethylene Vinyl Acetates (EVA). The later two were in the form of both emulsions and redispersible powders. Experiments concentrated on: (1) Rheological behaviour of polymer modified cement pastes; (2) Workability of polymer modified mortars; (3) Influence of curing conditions on the pore size distribution and diffusion of chloride ions; (4) Bond strength of polymer modified cement and mortar patches; and (5) Microscopic examination and semi-quantitative analyses of the bulk and interfacial microstructures. The following main conclusions were reached: (1) The addition of polymer emulsions have a considerable influence on the workability of fresh cement pastes, the extent of this depending on the type of system used. (2) The rheological parameters of fresh polymer modified mortars can be established using a two-point workability test which may be used when comparing the properties of different systems at constant workability. (3) Curing conditions affect the properties of polymer modified systems and a wet/dry curing regime was essential for good adhesion of these materials to mortar substrates. (4) In contrast, the wet/dry curing regime resulted in a curing affected zone at the surface of patch materials. This can result in a much coarser pore structure and enhanced diffusion of e.g. chloride ions. (5) The microstructure of polymer modified systems was very different compared with the unmodified cement/mortar and varied depending on curing conditions.

Income distribution dependence of poverty measure:a theoretical analysis

Using a modified deprivation (or poverty) function, in this paper, we theoretically study the changes in poverty with respect to the 'global' mean and variance of the income distribution using Indian survey data. We show that when the income obeys a log-normal distribution, a rising mean income generally indicates a reduction in poverty while an increase in the variance of the income distribution increases poverty. This altruistic view for a developing economy, however, is not tenable anymore once the poverty index is found to follow a pareto distribution. Here although a rising mean income indicates a reduction in poverty, due to the presence of an inflexion point in the poverty function, there is a critical value of the variance below which poverty decreases with increasing variance while beyond this value, poverty undergoes a steep increase followed by a decrease with respect to higher variance. Identifying this inflexion point as the poverty line, we show that the pareto poverty function satisfies all three standard axioms of a poverty index [N.C. Kakwani, Econometrica 43 (1980) 437; A.K. Sen, Econometrica 44 (1976) 219] whereas the log-normal distribution falls short of this requisite. Following these results, we make quantitative predictions to correlate a developing with a developed economy. © 2006 Elsevier B.V. All rights reserved.

Chitosan-modified dry powder formulations for pulmonary gene delivery

Spray-drying is an effective process for preparing micron-dimensioned particles for pulmonary delivery. Previously, we have demonstrated enhanced dispersibility and fine particle fraction of spray-dried nonviral gene delivery formulations using amino acids or absorption enhancers as dispersibility-enhancing excipients. In this study, we investigate the use of the cationic polymer chitosan as a readily available and biocompatible dispersibility enhancer. Lactose-lipid:polycation:pDNA (LPD) powders were prepared by spray-drying and post-mixed with chitosan or spray-dried chitosan. In addition, the water-soluble chitosan derivative, trimethyl chitosan, was added to the lactose-LPD formulation before spray-drying. Spray-dried chitosan particles, displaying an irregular surface morphology and diameter of less than 2 mu m, readily adsorbed to lactose-LPD particles following mixing. In contrast with the smooth spherical surface of lactose-LPD particles, spray-dried trimethyl chitosan-lactose-LPD particles demonstrated increased surface roughness and a unimodal particle size distribution (mean diameter 3.4 mu m), compared with the multimodal distribution for unmodified lactose-LPD powders (mean diameter 23.7 mu m). The emitted dose and in vitro deposition of chitosan-modified powders was significantly greater than that of unmodified powders. Moreover, the inclusion of chitosan mediated an enhanced level of reporter gene expression. In summary, chitosan enhances the dispersibility and in vitro pulmonary deposition performance of spray-dried powders.