The application of electrostatic dry powder deposition technology to coat drug-eluting stents

Purpose: A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles. Methods: Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces. Results: The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion. Conclusions: EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.

Synthesis and properties of polyelectrolyte microgel particles

A series of cationic poly(N-isopropylacrylamide/4-vinylpyridine) [poly(NIPAM/4-VP)] polyelectrolyte co-polymer microgels have been prepared by surfactant free emulsion polymerization (SFEP) with varying compositions of 4-VP and NIPAM. The compositions of 4-VP were 15, 25, 35, 45, 55 wt.% relative to NIPAM. The temperature and pH responsive swelling–deswelling properties of these microgels have been investigated using dynamic light scattering (DLS) and electrophoretic mobility measurements. DLS results have shown that the particle diameter of the poly(NIPAM/4-VP) microgels decreases with increasing concentration (wt.%) of 4-VP over the 20–60 °C temperature range due to the increased amount of hydrophobic group. The particle size of all poly(NIPAM/4-VP) microgel series increases with decreasing pH, as the 4-VP units become more protonated at low pH below the pKa (5.39) of the monomer 4-VP. Electrophoretic mobility results have shown that electrophoretic mobility increases as the temperature/pH increases at a constant background ionic strength (1 × 10− 4 mol dm− 3 NaCl). These results are in good agreement with DLS results. The temperature/pH sensitivity of these microgels depends on the ratio of NIPAM/4-VP concentration in the co-polymer microgel systems. The combined temperature/pH responsiveness of these polyelectrolyte microgels can be used in applications where changes in particle size with small change in pH or temperature is of great consequence.

Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer technique

An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations.

In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads

In recent years, the use of swelling polymeric matrices for the encapsulation and controlled release of protein drugs has received significant attention. The purpose of the present study was to investigate the release of albumin, a model protein from alginate/hydroxypropyl-methylcellulose (HPMC) gel beads. A hydrogel system comprised of two natural, hydrophilic polymers; sodium alginate and HPMC was studied as a carrier of bovine serum albumin (BSA) which was used as a model protein. The morphology, bead size and the swelling ratio were studied in different physical states; fully swollen, dried and reswollen using scanning electron microscopy and image analysis. Finally the effect of different alginate/HPMC ratios on the BSA release profile in physiological saline solution was investigated. Swelling experiments revealed that the bead diameter increases with the viscosity of the alginate solution while the addition of HPMC resulted in a significant increase of the swelling ratio. The BSA release patterns showed that the addition of HPMC increased the protein-release rate while the release mechanism fitted the Peppas model. Alginate/HPMC beads prepared using the ionic gelation exhibited high BSA loading efficiency for all formulations. The presence of HPMC increased the swelling ability of the alginate beads while the particle size remained unaffected. Incorporation of HPMC in the alginate gels also resulted in improved BSA release in physiological saline solution. All formulations presented a non-Fickian release mechanism described by the Peppas model. In addition, the implementation of non-parametric tests showed significant differences in the release patterns between the alginate/HPMC and the pure alginate beads, respectively.

Direct measurement of powder flavour adhesion on to a food surface using a novel adhesion tester

The firm adhesion of flavouring particles onto crisp surfaces during coating processes is a major concern in the snack production industry. Detachment of flavouring powders from products during handling and production stages can lead to substantial financial losses for the industry, in terms of variable flavour performance and extended cleaning down time of fugitive particle build-up on process equipment. Understanding the adhesion strength of applied bulk particulates used for flavouring formulations will help analysts to evaluate the efficiency of coating processes and potentially enable them to assess the adhesion strength of newly formulated flavouring powder prior to commitment to full scale plant trials. A rapid prototype of a novel adhesion tester has been designed and constructed. The apparatus operates according to the principle of impact force acting on particles attached to the surface of the food substrate. The main component is a circular plate to which four sample holders are attached and which is subjected to vertical travel down a guide shaft. Several flavouring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavouring powders (which is a strong function of particle size) has been discussed.

Influence of solder paste components on rheological behaviour

Rheological properties of solder pastes are very important for a high quality surface mount technology process. The stencil/screen printing process of solder pastes is one of the most critical steps in the SMT assembly process, as most of the assembly defects can often be shown to originate from paste rheology and associated poor printing performance. This paper concerns an investigation of the effect of solder paste composition on the rheological properties and behaviour of four different solder pastes. We report on the evaluation of three different paste formulations based on the no-clean flux composition, with different alloy composition, metal content and particle size using a range of rheological characterisation techniques - including viscosity measurements, yield stress, oscillatory and creep-recovery tests. Our results show that in the viscosity test, all solder pastes exhibited a shear thinning behaviour in nature with different highest maximum viscosity. In the region of shear thinning behaviour the paste 3 delivered the best results. Viscosity test helps to understand the solid and cohesive behaviour of solder pastes. Good solid and cohesive behaviour indicates a good paste roll and helps to avoid paste bleeding. The yield stress test has been used to study the effect of temperature on the flow behaviour of solder pastes. Yield stress was measured for a range of temperature from 15deg C to 35deg C with an increment of 5degC. The result indicated a decreasing of the yield stress point if the temperature was increased. Paste 4 has shown the minimum dependence on temperature. The oscillatory test has been used to find out the linear visco-elastic range and to study the solid and liquid like behaviours of solder pastes. Paste 1 indicated the biggest linear visco-elastic region (LVR) and the highest value of G' and G" which means solder paste 1 will be needed a higher squeegee pressure in the printing process. In the creep recovery test paste 4 showed the best- - recovery and the lowest values of creep and recovery compliance which indicated a good printing behaviour. The test also has showed the solder paste with smaller particle size exhibit less recovery

The Application Of Radioisotopes In The Study Of Estuarine Sedimentary Processes

The spatial and temporal distributions of some radionuclides in effluents originating from the British Nuclear Fuels Ltd (BNFL) reprocessing plant at Windscale, which are released into the Irish Sea, have been studied in sediments at 16 sites in the salt marsh region near Newbiggin on the Esk estuary Cumbria, England. The concentration of non-conservative radionuclides in surface sediments of the area cannot be described by a single parameter, but there is a high correlation with organic C, Cu, Al and the Si : Al ratio with particle size. The preservation of the historical record of the BNFL effluents in the Esk sediments is dependent on the hydrology of the area, as it effects such processes as accretion, erosion and remixing. From the 106Ru and 210Po concentrations and the 137Cs : 134Cs ratio in the sediment profiles with depth, we have identified these processes. Sedimentation rates at sites of accretion vary between 0·5 and 3 cm year−1. However, at some sites they appear to be much higher, approximately 6 cm year−1 in the top 10 cm, but they are not consistent throughout the depth profiles. This may be a true reflection of variable accretion related to sediment type, or one which is influenced by surficial mixing. Some cores showed evidence of continuous accretion but no significant radioactivity was detected at depths below 35–40 cm, indicating an overall sedimentation rate of approximately 1·5 cm year−1 for the 25–30-year period since BNFL effluents first entered the Irish Sea.

Relationships Between Seston Available Food And Feeding-Activity In The Common Mussel Mytilus-Edulis

The feeding and metabolic rates of Mytilus edulis L. of different body sizes were measured in response to changes in particle concentrations ranging from 2 to 350 mg l-1. Rates of oxygen consumption were not significantly affected by changes in seston concentration, whereas clearance rates gradually declined with increasing particle concentration. Pseudofaeces production was initiated at relatively low seston concentrations (<5 mg l-1). Marked seasonal changes were recorded in the composition of suspended particulates (seston) in an estuary in south-west England. Total seston was sampled at frequent intervals throughout an annual cycle and analysed in terms of: particle size-frequency distributions, total dry weight (mg l-1), inorganic content, chlorophyll a, carbohydrate, protein and lipid. The particulate carbohydrate, protein and lipid content provided an estimate of the food content of the seston. The results are discussed in terms of the “food available” to a nonselective suspension feeder, such as M. edulis, during a seasonal cycle. The effect of inorganic silt in suspension was mainly to limit by “dilution” the amount of food material ingested rather than to reduce the amount of material filtered by the mussel. In winter, the food content of the material ingested was 5%, and this increased to 25% during the spring and summer.

Acceptance angle effects on the beam attenuation in the ocean

The beam attenuation serves as a proxy for particulate matter and is a key parameter in visibility algorithms for the aquatic environment. It is well known, however, that the beam attenuation is a function of the acceptance angle of the transmissometer used to measure it. Here we compare eight different transmissometers with four different acceptance angles using four different deployment strategies and sites, and find that their mean attenuation values differ markedly and in a consistent way with instrument acceptance angle: smaller acceptance angles provide higher beam attenuation values. This difference is due to variations in scattered light collected with different acceptance angles and is neither constant nor easy to parameterize. Variability (in space or time) in the ratios of beam attenuations measured by two different instruments correlates, in most cases, with the particle size parameter (as expected from Mie theory), but this correlation is often weak and can be the opposite of expectations based on particle size changes. We recommended careful consideration of acceptance angle in applications of beam transmission data especially when comparing data from different instruments. (C) 2009 Optical Society of America

Global assessment of ocean carbon export by combining satellite observations and food-web models

The export of organic carbon from the surface ocean by sinking particles is an important, yet highly uncertain, component of the global carbon cycle. Here we introduce a mechanistic assessment of the global ocean carbon export using satellite observations, including determinations of net primary production and the slope of the particle size spectrum, to drive a food-web model that estimates the production of sinking zooplankton feces and algal aggregates comprising the sinking particle flux at the base of the euphotic zone. The synthesis of observations and models reveals fundamentally different and ecologically consistent regional-scale patterns in export and export efficiency not found in previous global carbon export assessments. The model reproduces regional-scale particle export field observations and predicts a climatological mean global carbon export from the euphotic zone of ~6 Pg C yr−1. Global export estimates show small variation (typically < 10%) to factor of 2 changes in model parameter values. The model is also robust to the choices of the satellite data products used and enables interannual changes to be quantified. The present synthesis of observations and models provides a path for quantifying the ocean's biological pump.

Influence of process parameters on fluidised hot-melt granulation and tablet pressing of pharmaceutical powders

This study investigates the influence of process parameters on the fluidised hot melt granulation of lactose and PEG 6000, and the subsequent tablet pressing of the granules. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed on the resulting granule properties such as mass mean granule size, size distribution, granule fracture stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in this melt granulation system were nucleation followed by steady growth (PEG 10–20% w/w). However, with binder contents greater than 20% w/w, the granulation mechanism moved to the “over-wet massing” regime in which discrete granule formation could not be obtained. The granules produced in the melt fluidised bed process were subsequently pressed into tablets using an industrial tablet press. The physical properties of the tablets: fracture stress, disintegration time and friability were assessed using industry standards. These analyses indicated that particle size and binder content of the initial granules influenced the mechanical properties of the tablets. It was noted that a decrease in initial granule size resulted in an increase in the fracture stress of the tablets formed.

Bimetallic effects in the liquid phase hydrogenation of 2-butanone

A series of bimetallic Ru-containing monometallic and bimetallic catalysts were prepared and tested for their activity for the hydrogenation of 2-butanone to 2-butanol at 30 °C and 3 bar H2. RuPt bimetallic catalysts were the most active for the reaction, with a ratio of 5 wt% Ru:1 wt% Pt on activated carbon (AC) found to be optimum. The activity of this bimetallic catalyst was more than double that of the sum of the activities of the monometallic Ru and Pt catalysts, providing evidence of a “bimetallic” effect. Structural analysis of the bimetallic catalysts revealed that they consisted of clusters of particles of the order of 1–2 nm. Extended X-ray absorption fine structure analysis showed that there were two types of particle on the surface of the bimetallic RuPt catalyst, specifically monometallic Ru and bimetallic RuPt particles. For the bimetallic particles, it was possible to fit the data with a model in which a Ru core of 1.1 nm is enclosed by two Pt-rich layers, the outer layer containing only 13 at% Ru. Pretreatment of the monometallic and bimetallic catalysts in hydrogen had a significant effect on the activity. Both the bimetallic and monometallic Ru-based catalysts showed a trend of decreasing activity with increasing temperature of prereduction in hydrogen. This loss of activity was almost fully reversible by exposure of the catalysts to air after reduction. The changing activity with exposure to different gas phase environments could not be attributed to changes in particle size or surface composition. It is proposed that the introduction of hydrogen results in a gradual smoothing of the surface and loss of defect sites; this process being reversible on introduction of air. These defect sites are particularly important for the dissociative adsorption of hydrogen, potentially the rate-determining step in this reaction.

Organisational controls, typologies and time scales of paraglacial gravel-dominated coastal systems

The fundamental controls on the initiation and development of gravel-dominated deposits (beaches and barriers) on paraglacial coasts are particle size and shape, sediment supply, storm wave activity (primarily runup), relative sea-level (RSL) change, and terrestrial basement structure (primarily as it affects accommodation space). This paper examines the stochastic basis for barrier organisation as shown by variation in gravel barrier architecture. We recognise punctuated self-organisation of barrier development that is disrupted by short phases of barrier instability. The latter results from positive feedback causing barrier breakdown when sediment supply is exhausted. We examine published typologies for gravel barriers and advocate a consolidated perspective using rate of RSL change and sediment supply. We also consider the temporal variation in controls on barrier development. These are examined in terms of a simple behavioural model (BARCH) for prograding gravel barrier architecture and its sensitivity to such controls. The nature of macroscale (102–103 years) gravel barrier development, including inherited characteristics that influence barrier genesis, as well as forcing from changing RSL, sediment supply, headland control and barrier inertia, is examined in the context of long-surviving barriers along the southern England coastline.

Reuse of construction waste: performance under repeated loading

The use of recycled aggregates has increased greatly over the last decade owing to enhanced environmental sensitivities. The level of performance required by such materials is dependent upon the applications for which they are used. Many recycled construction wastes have adequate shear strength in relation to various geotechnical applications. However, a possible drawback of these materials is the risk of crushing during repeated loading. The work reported in this paper examined two waste materials: crushed concrete and building debris, both regarded as construction wastes. Tests were also performed on traditionally used crushed rock, in this case basalt. The materials were subjected to repeated loading in a large direct shear apparatus. The amount of crushing was quantified by performing particle size analysis of the tested material. The results have shown that both recycled construction wastes were susceptible to particle crushing. The amount of crushing was influenced by both the vertical pressure and the number of loading cycles. This leads to a marked decrease in peak friction angle

Development of sampling methods for Raman analysis of solid dosage forms of therapeutic and illicit drugs

The results of a study aimed at determining the most important experimental parameters for automated, quantitative analysis of solid dosage form pharmaceuticals (seized and model 'ecstasy' tablets) are reported. Data obtained with a macro-Raman spectrometer were complemented by micro-Raman measurements, which gave information on particle size and provided excellent data for developing statistical models of the sampling errors associated with collecting data as a series of grid points on the tablets' surface. Spectra recorded at single points on the surface of seized MDMA-caffeine-lactose tablets with a Raman microscope (lambda(ex) = 785 nm, 3 mum diameter spot) were typically dominated by one or other of the three components, consistent with Raman mapping data which showed the drug and caffeine microcrystals were ca 40 mum in diameter. Spectra collected with a microscope from eight points on a 200 mum grid were combined and in the resultant spectra the average value of the Raman band intensity ratio used to quantify the MDMA: caffeine ratio, mu(r), was 1.19 with an unacceptably high standard deviation, sigma(r), of 1.20. In contrast, with a conventional macro-Raman system (150 mum spot diameter), combined eight grid point data gave mu(r) = 1.47 with sigma(r) = 0.16. A simple statistical model which could be used to predict sigma(r) under the various conditions used was developed. The model showed that the decrease in sigma(r) on moving to a 150 mum spot was too large to be due entirely to the increased spot diameter but was consistent with the increased sampling volume that arose from a combination of the larger spot size and depth of focus in the macroscopic system. With the macro-Raman system, combining 64 grid points (0.5 mm spacing and 1-2 s accumulation per point) to give a single averaged spectrum for a tablet was found to be a practical balance between minimizing sampling errors and keeping overhead times at an acceptable level. The effectiveness of this sampling strategy was also tested by quantitative analysis of a set of model ecstasy tablets prepared from MDEA-sorbitol (0-30% by mass MDEA). A simple univariate calibration model of averaged 64 point data had R-2 = 0.998 and an r.m.s. standard error of prediction of 1.1% whereas data obtained by sampling just four points on the same tablet showed deviations from the calibration of up to 5%.