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Concentration Profiles (concentration + profile)
Kinds of Concentration Profiles Selected AbstractsConfocal Raman Microscopy as a Tool to Investigate Concentration Profiles of Melt Crystallized Ibuprofen/Carnauba WaxCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 7 2009H. Qu Abstract Coatings are of great significance for pharmaceutical solid dosage forms. They fulfil a number of functions and are often necessary to control drug delivery, to mask bitter taste, or to protect the active pharmaceutical ingredient from detrimental environmental factors. The process of self-coating by melt crystallization of a suitable binary mixture eliminates the need for an additional process step in the manufacture of a solid drug. Self-coating relies upon the physical and spatial separation of individual components in a melt during solidification. This paper focuses on the use of confocal Raman microscopy as a nondestructive technique for quantifying the spatial distribution of the components in self-coated pastilles manufactured from the binary system ibuprofen/carnauba wax. Pastilles are produced from the melt. Raman spectroscopy allows the direct analysis of concentration profiles across the surface of the pastille. Here, the samples are cleaved and the cleaved surface is investigated in order to establish the distribution of the components in the interior of the solid. A univariate calibration model was developed and statistically validated with standard mixtures of ibuprofen and carnauba wax. Different regression models (linear or polynomial, using different significant peaks for the respective compounds) were assessed and a linear model was found to be adequate to determine the concentration gradient in the pastilles. [source] Development of a Segmented Model for a Continuous Electrophoretic Moving Bed Enantiomer SeparationBIOTECHNOLOGY PROGRESS, Issue 6 2003Brian M. Thome With the recent demonstration of a continuous electrophoretic "moving bed" enantiomer separation at mg/h throughputs, interest has now turned to scaling up the process for use as a benchtop pharmaceutical production tool. To scale the method, a steady-state mathematical model was developed that predicts the process response to changes in input feed rate and counterflow or "moving bed" velocities. The vortex-stabilized apparatus used for the separation was modeled using four regions based on the different hydrodynamic flows in each section. Concentration profiles were then derived on the basis of the properties of the Piperoxan-sulfated ,-cyclodextrin system being studied. The effects of different regional flow rates on the concentration profiles were evaluated and used to predict the maximum processing rate and the hydrodynamic profiles required for a separation. Although the model was able to qualitatively predict the shapes of the concentration profiles and show where the theoretical limits of operation existed, it was not able to quantitatively match the data from actual enantiomer separations to better than 50% accuracy. This is believed to be due to the simplifying assumptions involved, namely, the neglect of electric field variations and the lack of a competitive binding isotherm in the analysis. Although the model cannot accurately predict concentrations from a separation, it provides a good theoretical framework for analyzing how the process responds to changes in counterflow rate, feed rate, and the properties of the molecules being separated. [source] Effects of spatial variations in source areas upon dust concentration profiles during three wind erosion events in AustraliaEARTH SURFACE PROCESSES AND LANDFORMS, Issue 10 2001H. J. Butler Abstract Dust storms are a major contributor to soil erosion in inland Australia, and the Simpson Desert,Channel Country region is one of the most active wind erosion regions. While information is available on wind erosion rates at the land-type level, little is known about the influence that spatial variations in the erodibility within a land type have on the resulting dust concentration profile. A Gaussian plume model, DSIS, is presented along with tower-based dust data, to describe the influence of different spatial combinations of dust source areas, during three dust events on the Diamantina River floodplain in Western Queensland, Australia. Copyright © 2001 John Wiley & Sons, Ltd. [source] Vigabatrin extracellular pharmacokinetics and concurrent ,-aminobutyric acid neurotransmitter effects in rat frontal cortex and hippocampus using microdialysisEPILEPSIA, Issue 2 2009Xin Tong Summary Purpose:, To investigate the pharmacokinetic interrelationship of vigabatrin in blood and the brain (frontal cortex vs. hippocampus) and to ascertain the relationship between brain extracellular vigabatrin concentrations and concurrent ,-aminobutyric acid (GABA) concentrations. Methods:, Sprague-Dawley rats were implanted with a jugular vein catheter for blood sampling, and microdialysis probes in the frontal cortex and hippocampus for extracellular fluid (ECF) sampling. Vigabatrin was administered intraperitoneally at two different doses (500 and 1,000 mg/kg), and blood and ECF were collected at timed intervals up to 8 h. Rats were freely moving and behaving. Vigabatrin (sera and ECF) and GABA (ECF) concentrations were measured with use of high performance liquid chromatography (HPLC). Results:, Vigabatrin concentrations in blood rose linearly and dose-dependently, and vigabatrin rapidly appeared in the brain as evidenced by the detection of vigabatrin in the ECF of both the frontal cortex and hippocampus at time of first sampling (15 min). However, frontal cortex concentrations were twofold greater than those of the hippocampus. Furthermore, GABA concentrations increased five-fold in the frontal cortex but were unaffected in the hippocampus. In addition, GABA concentrations began to increase approximately 3 h after vigabatrin administration at a time when vigabatrin concentrations were in exponential decline. Conclusions:, Vigabatrin distribution in the brain is region specific, with frontal cortex concentrations substantially greater than those seen in the hippocampus. Elevation of GABA concentrations did not reflect the concentration profile of vigabatrin but reflected its regional distribution. [source] Automated diffusion chambers to monitor diurnal and seasonal dynamics of the soil CO2 concentration profileEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 4 2009F. Albanito Summary To better understand the factors controlling carbon dioxide (CO2) production and transport in soil, we developed a new method to continuously monitor soil CO2 concentration at multiple depths, by using diffusion chambers. The soil diffusion chambers are constructed from a high-density polyethylene cylindrical frame enclosed by a micro-polyvinylidene difluoride flat membrane (PVDF). All chambers are linked to an infrared gas analyser positioned above-ground through a multi-port valve system. We set up two experimental sites for long-term measurements of soil CO2 concentration, soil temperature and soil water content at depths of 0, 10, 20, 40 and 80 cm. The system provides the following advantages : (i) the use of the PVDF combined with the small dimensions of the diffusion chambers allows rapid diffusion of soil gas into the chambers and therefore a short equilibration time of the gas phase with the surrounding soil atmosphere, (ii) the equilibrating closed loop system allows the semi-continuous measurement of soil profile CO2 concentrations without creating a pressure differential within the chambers, thus reducing gas concentration distortions in the soil, (iii) the small size of the closed diffusion chambers reduces the initial soil disturbance during installation, (iv) it allows sampling in wet, humid soils, including ones that are waterlogged or temporarily saturated, and (v) the chambers do not require removal for maintenance purposes and are inexpensive. [source] Modelling night-time ecosystem respiration by a constrained source optimization methodGLOBAL CHANGE BIOLOGY, Issue 2 2002Chun-Ta Lai Abstract One of the main challenges to quantifying ecosystem carbon budgets is properly quantifying the magnitude of night-time ecosystem respiration. Inverse Lagrangian dispersion analysis provides a promising approach to addressing such a problem when measured mean CO2 concentration profiles and nocturnal velocity statistics are available. An inverse method, termed ,Constrained Source Optimization' or CSO, which couples a localized near-field theory (LNF) of turbulent dispersion to respiratory sources, is developed to estimate seasonal and annual components of ecosystem respiration. A key advantage to the proposed method is that the effects of variable leaf area density on flow statistics are explicitly resolved via higher-order closure principles. In CSO, the source distribution was computed after optimizing key physiological parameters to recover the measured mean concentration profile in a least-square fashion. The proposed method was field-tested using 1 year of 30-min mean CO2 concentration and CO2 flux measurements collected within a 17-year-old (in 1999) even-aged loblolly pine (Pinus taeda L.) stand in central North Carolina. Eddy-covariance flux measurements conditioned on large friction velocity, leaf-level porometry and forest-floor respiration chamber measurements were used to assess the performance of the CSO model. The CSO approach produced reasonable estimates of ecosystem respiration, which permits estimation of ecosystem gross primary production when combined with daytime net ecosystem exchange (NEE) measurements. We employed the CSO approach in modelling annual respiration of above-ground plant components (c. 214 g C m,2 year,1) and forest floor (c. 989 g C m,2 year,1) for estimating gross primary production (c. 1800 g C m,2 year,1) with a NEE of c. 605 g C m,2 year,1 for this pine forest ecosystem. We conclude that the CSO approach can utilise routine CO2 concentration profile measurements to corroborate forest carbon balance estimates from eddy-covariance NEE and chamber-based component flux measurements. [source] Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di- tert -butyl 4-nitrophenol, in grafted human skinJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2006Lynn K. Pershing Abstract Disposition and uptake/elimination profiles of topical 2,6-di- t -butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 µg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 ± 602 µg cm,3, and ,30 and ,300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0,24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mathematical modeling of gas-phase biofilter performanceJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 7 2003Hasnaa Jorio Abstract In the present paper, a new mathematical model describing the physical, chemical and biological phenomena involved in the process of contaminant removal in biofilters is developed. In addition to the contaminant, the key components of the present theoretical model are carbon dioxide and oxygen. The model predicts the concentration profile of the key components in the gas phase, the biofilm and the sorption liquid retained in the solid particles composing the filter bed at both steady and transient regimes. The model equations were solved numerically and comparison between theory and experiment showed that the model results for styrene and carbon dioxide concentration profiles were in very good agreement with experimental data for the biofiltration of styrene vapors at steady state. The analysis of oxygen concentration profile in the biofilm predicted by the theoretical model revealed that oxygen limitation does not occur under the operating styrene biodegradation rate in the biofilter. Copyright © 2003 Society of Chemical Industry [source] FRUIT BRANDY PRODUCTION BY BATCH COLUMN DISTILLATION WITH REFLUXJOURNAL OF FOOD PROCESS ENGINEERING, Issue 1 2005MICHAEL J. CLAUS ABSTRACT The relationship between the operating parameters of batch fruit spirits column stills with reflux and the congener (trace compounds that provide flavors and aromas) concentrations in resulting fruit spirits has not been widely studied. Congener concentrations were determined in three different collection fractions, or "cuts," during batch distillation. Acetaldehyde and ethyl acetate were found in higher concentrations in the head cut, first overhead fraction, of the distillation and have lower boiling points relative to ethanol. 1-Propanol and isoamyl alcohol (isopentanol) were present in higher concentrations in the tail cut, third or final fraction, of the distillation and have boiling points that are higher than ethanol. Methanol has a unique concentration profile as it has higher concentrations in both the head and tail cuts, but a lower concentration in the heart cut, the middle fraction which is the desired product of the distillation. Methanol was of particular interest because the distillate must adhere to governmental regulations that limit its concentration in the product. Operating-condition parameters that were studied include the number of trays used in the distillation as well as the use of a "catalytic converter," a high surface, copper-packing material thought to catalyze formation of cyanide-containing compounds allowing them to be separated from the distillate. The effect of the number of trays used in a distillation on the concentration of ethanol and the congeners, methanol, acetaldehyde, ethyl acetate, 1-propanol and isoamyl alcohol in the final distilled spirits product is presented. An additional result of acetaldehyde production at the copper surface of the catalytic converter was also discovered in the analysis of the data. [source] Experimental and numerical research for fluidization behaviors in a gas,solid acoustic fluidized bedAICHE JOURNAL, Issue 7 2010Changqing Cao Abstract The effects of sound assistance on fluidization behaviors were systematically investigated in a gas,solid acoustic fluidized bed. A model modified from Syamlal,O'Brien drag model was established. The original solid momentum equation was developed and an acoustic model was also proposed. The radial particle volume fraction, axial root-mean-square of bed pressure drop, granular temperature, and particle velocity in gas,solid acoustic fluidized bed were simulated using computational fluid dynamics (CFD) code Fluent 6.2. The results showed that radial particle volume fraction increased using modified drag model compared with that using the original one. Radial particle volume fraction was revealed as a parabolic concentration profile. Axial particle volume fraction decreased with the increasing bed height. The granular temperature increased with increasing sound pressure level. It showed that simulation values using CFD code Fluent 6.2 were in agreement with the experimental data. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Recovery of transition metal complex by reverse flow adsorptionAICHE JOURNAL, Issue 1 2008Jeroen Dunnewijk Abstract Reverse flow adsorption (RFA) is a technique with a definite potential to prevent the leaching of a homogenous catalyst. In this work, we model an RFA-process for a continuous ideally stirred tank reactor with an adsorption bed upstream and another one downstream from the reactor. The model parameters concerning adsorption equilibrium and kinetics are taken from previous experimental studies on CoCl2 adsorption on polymer-bound trifenylfosfine. We use this model to study the concentration profiles of CoCl2 in the adsorption beds during consecutive adsorption,desorption cycles. The model calculations show that the concentration profile eventually reaches a fixed position after a number of adsorption,desorption cycles, even though internal mass transfer was a limiting factor. Hence, the transition metal is kept within the system boundaries, which is an essential requirement for the application of RFA. © 2007 American Institute of Chemical Engineers AIChE J, 2008 [source] Volume of distribution at steady state for a linear pharmacokinetic system with peripheral eliminationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Leonid M. Berezhkovskiy Abstract The problem of finding the steady-state volume of distribution Vss for a linear pharmacokinetic system with peripheral drug elimination is considered. A commonly used equation Vss,=,(D/AUC)*MRT is applicable only for the systems with central (plasma) drug elimination. The following equation, Vss,=,(D/AUC)*MRTint, was obtained, where AUC is the commonly calculated area under the time curve of the total drug concentration in plasma after intravenous (iv) administration of bolus drug dose, D, and MRTint is the intrinsic mean residence time, which is the average time the drug spends in the body (system) after entering the systemic circulation (plasma). The value of MRTint cannot be found from a drug plasma concentration profile after an iv bolus drug input if a peripheral drug exit occurs. The obtained equation does not contain the assumption of an immediate equilibrium of protein and tissue binding in plasma and organs, and thus incorporates the rates of all possible reactions. If drug exits the system only through central compartment (plasma) and there is an instant equilibrium between bound and unbound drug fractions in plasma, then MRTint becomes equal to MRT,=,AUMC/AUC, which is calculated using the time course of the total drug concentration in plasma after an iv bolus injection. Thus, the obtained equation coincides with the traditional one, Vss,=,(D/AUC)*MRT, if the assumptions for validity of this equation are met. Experimental methods for determining the steady-state volume of distribution and MRTint, as well as the problem of determining whether peripheral drug elimination occurs, are considered. The equation for calculation of the tissue,plasma partition coefficient with the account of peripheral elimination is obtained. The difference between traditionally calculated Vss,=,(D/AUC)*MRT and the true value given by (D/AUC)*MRTint is discussed. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1628,1640, 2004 [source] Modeling of protein breakthrough performance in cryogel columns by taking into account the overall axial dispersionJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15-16 2009Junxian Yun Abstract A model considering the overall axial dispersion for describing protein adsorption and breakthrough in monolithic cryogel beds has been developed. The microstructure of cryogels was characterized by tortuous capillaries with a normal diameter distribution but a constant pore wall thickness. The axial dispersion within cryogel columns was described by using the overall axial dispersion coefficient, which can be easily obtained by matching the experimental breakthrough curves without adsorption or measuring residence time distributions (RTDs). Experimental breakthrough curves of lysozyme within a metal-chelated affinity cryogel by Persson et al. (Biotechnol. Bioeng. 2004, 88, 224,236) and a cation-exchange cryogel by Yao et al. (J. Chromatogr. A 2007, 1157, 246,251) were employed as examples to test the model. The results showed that by using the axial dispersion coefficient and assuming uniform radial concentration profile at a given cross-section of the cryogel along the bed height, the model can describe the detailed behaviors of the in-bed overall axial dispersion, the in-pore mass transfer, as well as the protein adsorption and breakthrough. For a known overall axial dispersion coefficient, the lumped parameter of the mass transfer coefficient between the bulk liquid and the capillary wall can be determined by fitting the protein breakthrough curve at a known chromatographic condition. Once this parameter is determined, the model can be used to predict the protein breakthrough profiles under different conditions based on the basic physical parameters of the cryogel bed and the properties of the fluid and protein. The effective capillary diameters employed in the model are close to the actual pore sizes observed from the images by SEM. The model predictions of lysozyme breakthrough profiles at various flow rates are also in good agreement with the experimental data in both the metal-chelated affinity and cation-exchange cryogel columns. [source] Modeling the Effect of Oxygen on Photopolymerization KineticsMACROMOLECULAR THEORY AND SIMULATIONS, Issue 2 2006Allison K. O'Brien Abstract Summary: A comprehensive one-dimensional photopolymerization model was utilized to investigate the effect of oxygen on the free-radical photopolymerization kinetics. The spatial profiling aspect of the model provided insight into the heterogeneity of the cure kinetics due to oxygen inhibition, specifically the variance in the concentration profile of monomer and oxygen. Double bond conversion was negligible for the top ten microns of the film due to continuous oxygen diffusion, and increased with increasing depth. Similarly, the oxygen concentration decreased with increasing depth due to the competition between oxygen diffusion time and the polymerization rate. The effect of initiation rate on the extent of oxygen inhibition was investigated for various oxygen concentrations. As the initiation rate increased, the polymerization rate increased, and eventually approached that of a sample in an inert environment. Similarly, as the oxygen concentration was decreased, the polymerization rate increased. The effect of varying the initiation rate on the cure profile in the oxygen-exposed film was also studied. It was found that the unpolymerized tacky layer decreased from 50 µm to 5 µm with a 3 order of magnitude increase in initiation rate. Using the pseudo steady state approximation, the relationship between polymerization rate and initiation rate was derived for films in an oxygen environment. A direct relationship between the polymerization and initiation rate was found for films in air. The polymerization model supported this derivation and found that as the oxygen concentration was decreased, the dependence on initiation rate, or alpha, decreased, reaching the accepted value of 0.5 for alpha in inert environments. Double bond conversion versus film depth and cure time. [source] Planar Droplet Sizing for the Characterization of Droplet Clusters in an Industrial Gun-Type BurnerPARTICLE & PARTICLE SYSTEMS CHARACTERIZATION, Issue 3 2003Laurent Zimmer Abstract An important problem in spray combustion deals with the existence of dense regions of droplets, called clusters. To understand their formation mechanism, the droplet dynamics and fuel concentration profile are investigated by means of planar laser techniques in an industrial gun-type burner. The simultaneous measurement of elastic Mie scattering and Laser Induced Fluorescence (LIF) allows the instantaneous measurement of the Sauter Mean Diameter (SMD), after proper calibration. Using two different CCDs to get the two signals requires a detailed calibration of the CCD response before getting absolute diameters. Pixels are binned 6 by 6 to obtain the final SMD map, this is a compromise between spatial accuracy and noise. Velocity field is measured on both sets of images using standard Particle Image Velocimetry (PIV) algorithms. The comparison of cross-correlation technique with PDA results shows that the velocity measured on the LIF images are close to the velocity based on D30, whereas the Mie scattering results are similar to D20. On Mie scattering images, regions of high interfacial area forming clusters can be detected. A special tracking scheme is used to characterize their dynamics in terms of velocity and diameters by ensuring that the same volume of fluid is tracked. It is shown that the clusters have a velocity similar to the velocity of droplets with the same diameter as the mean SMD of the cluster. It is also shown that an increase of pressure tends to trigger the appearance of such a group of droplets, due to a smaller diameter of the droplets caused by the increase of pressure discharge. Uncertainties for the different techniques used are discussed. [source] Investigation of graded index SiOxNy antireflection coating for silicon solar cell manufacturingPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 4 2007M. Lipi Abstract An optimization of SiOxNy anti-reflective coatings with graded index layers for silicon solar cells based on the Bruggeman's effective medium approximation is presented. For simulation of reflectance and absorption of graded layer, the experimental optical data of silicon nitride SiNx:H and oxynitride SiOxNy obtained by Low Frequency (440 kHz) Plasma Enhanced Chemical Vapour Deposition (LF-PECVD) were used. We have shown that the graded index oxynitride antireflection coating can reduce the effective reflectance to about 2.5% but the high absorption due to high extinction coefficient compensates this improvement and reduces the short circuit current (Jsc) of the solar cell. The improvement in the Jsc can be obtained for graded SiNxOy layer with smaller value of refractive index of SiNx (n = 2.2). In this case the graded SiOxNy layer is characterized by an abrupt concentration profile and can be considered as a double antireflection coating SiO2/SiNx. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Concentration of aqueous dye solution by freezing and thawingTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 5 2009Kyuya Nakagawa Abstract The concentration phenomena during freezing and thawing were investigated to study the feasibility of freeze,thaw process as a concentration operation. An aqueous dye solution was employed as a model binary eutectic solution. The localised concentration in the frozen matrix was determined, and the concentration profile of the melting solution during thawing was examined. It was found that the solution obtained during thawing showed higher concentration than the original solution, and the concentration did not correspond to the amount of solute localised in the frozen matrix. It was suggested that the concentration phenomena during thawing would be governed by the melting droplet growth rate at the melting interface and by the diffusion rate of solute from eutectic phases to the droplet. On a observé le phénomène de la concentration durant le gel et le dégel afin de déterminer la faisabilité du processus de gel et de dégel en tant qu'opération de concentration. On a utilisé une solution colorante aqueuse comme solution eutectique binaire de modèle. On a déterminé la concentration localisée dans la matrice congelée et examiné le profil de concentration de la solution durant la décongélation. On a noté que la solution obtenue durant la décongélation présentait une concentration supérieure à la solution d'origine, et que la concentration ne correspondait pas à la quantité de soluté localisée dans la matrice congelée. Il a été suggéré que le phénomène de concentration durant le dégel serait régi par le taux de croissance des gouttelettes issues de la fonte à la surface et par le taux de diffusion du soluté à partir des phases eutectiques à la gouttelette. [source] Analysis of the influence of coupled diffusion on transport in protein crystal growth for different gravity levelsACTA CRYSTALLOGRAPHICA SECTION D, Issue 10-1 2002D. Castagnolo Diffusion has a central role in protein crystal growth both in microgravity conditions and on ground. Recently several reports have been focused on the importance to use the generalized Fick's equations in n -component systems where crystals grow. In these equations the total flux of each component is produced by the own concentration gradient (main flow) and by the concentration gradient of the other components (cross-flow) present in the system. However in literature the latter effect is often neglected, and the so-called pseudo-binary approximation is used. Lin et al. (1995) proposed a mathematical model to evaluate the concentration profile of the species present around a growing protein crystal. Although the model is reliable, it suffers of the pseudo-binary approximation (neglecting cross term diffusion coefficients and using binary diffusion coefficients), probably because of the lack of multicomponent diffusion data. The present model is based on the experimental set-up proposed by Lin et al. (1995). Nevertheless we have included the coupled diffusion effects, according to the correct description of the matter transport through the generalized Fick's equations. The crystal growth rate is calculated for different gravity levels. The model has been applied to the ternary lysozyme-NaCl-water and quaternary lysozyme-poly(ethylene glycol) (PEG)-NaCl-water systems using recent diffusion data. [source] Bioavailability of modified-release methylphenidate: influence of high-fat breakfast when administered intact and when capsule content sprinkled on applesauceBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2003Lucy Lee Abstract Ritalin®, an immediate release form of racemic methylphenidate hydrochloride, has been available in the USA since 1955 and is used for the treatment of ADHD. The objective of this study was to evaluate the pharmacokinetics of modified-release methylphenidate (highest single dose), Ritalin® LA, when administered under fasting condition, with a high-fat breakfast, and when sprinkled on applesauce in healthy adult subjects. Blood samples were drawn for 24 h following a 40 mg oral administration. Most subjects appeared to produce a bimodal methylphenidate plasma concentration profile. In all three treatment groups, methylphenidate was rapidly absorbed with an initial average tmax(0,4) of 1.3,2.4 h and an average peak plasma concentration [Cmax(abs)] of 14.4,15.2 ng/ml. On average, both the rate [Cmax(abs) and tmax(abs)] and the extent of absorption (AUC0,,) of methylphenidate were similar when the capsule was given with a high fat breakfast and when the capsule contents were sprinkled onto applesauce, compared with the fasting state. No dose dumping was observed when the capsule was given with a high fat breakfast or when sprinkled onto applesauce. The dose was safe and generally well tolerated. Coadministration of a single oral dose of 40 mg methylphenidate capsule whether administered intact with a high-fat breakfast or sprinkled on applesauce did not affect the overall rate or extent of absorption of methylphenidate compared with the fasted condition. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or anginaBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2002Suneel Gupta Abstract Aims: To study the dose-ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled-release verapamil in patients with hypertension. Methods: Dose-ranging studies were conducted in healthy volunteers and patients with hypertension and angina. Subjects received doses of 120, 180, 360, or 540 mg racemic verapamil as an osmotic controlled-release formulation. A population pharmacokinetic model involving zero-order release of verapamil into the gastrointestinal tract with first-order absorption and elimination was used to describe the steady-state plasma concentration profile for R - and S -verapamil. A population sigmoid Emax pharmacodynamic model was used to describe the effect of R - and S -verapamil on mean arterial blood pressure. Results:S -verapamil had an approximate 4-fold greater apparent clearance than R -verapamil in both healthy volunteers and patients. The apparent plasma clearance of R - and S -verapamil in healthy volunteers decreased over the dose range of 120,540 mg. A similar dose-dependent decrease in apparent plasma clearance was also noted in patients. None of the patient demographic variables examined (age, total body weight, lean body weight, body mass index, and height) explained the variability in verapamil pharmacokinetics. The pharmacodynamic model describing the relationship between verapamil plasma concentration and mean arterial blood pressure indicated that the S -verapamil had a 3.6-fold lower estimated EC50 compared to R -verapamil. Conclusions: The results from this dose-ranging pharmacokinetic investigation in healthy volunteers and patients are consistent with previous reports in healthy subjects. S -verapamil is cleared more rapidly than R -verapamil and the estimated EC50 for S -verapamil was 3.6-fold lower than for R -verapamil. Estimated EC50 values for R - and S -verapamil decreased with increasing age and decreasing weight. Copyright © 2002 John Wiley & Sons, Ltd. [source] Quantification of heparin-induced TFPI release: a maximum release at low heparin doseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2002Michiel J. B. Kemme Aims Heparin releases tissue factor pathway inhibitor (TFPI) from the endothelium and this release may decrease after repeated high dose heparin administration. The primary aim was to investigate and quantify this phenomenon during a short low dose heparin infusion. Also, the effects of heparin on tissue plasminogen activator (t-PA) were studied. Methods Nine healthy, nonsmoking, male volunteers (range 19,23 years) received a continuous heparin infusion (2000 IU) over 40 min. The endothelial TFPI release rate was estimated from the total TFPI concentration profile using a pharmacokinetic model. Results , Mean ,±,s.d. ,total ,and ,free ,TFPI ,increased ,from ,62.9 ± 9.4/8.3 ± 2.1 ng ml,1 at baseline to 237.2 ± 40.9/111.0 ± 19.9 ng ml,1 after 40 min infusion. The relationship between heparin concentration (anti-IIa activity) and TFPI concentration followed a maximum effect model and a clockwise loop (proteresis) was observed. The TFPI release rate rapidly increased to maximum of 200 ± 45 µg min,1 after 17.5 min heparin infusion but did not increase further although heparin concentrations further doubled. In contrast to TFPI, t-PA antigen decreased from 5.6 ± 1.0 at baseline to 4.5 ± 1.0 ng ml,1 at the end of infusion (t = 40 min) (difference of 1.1 ng ml,1 (95% confidence interval; 0.9, 1.3). Conclusions Our application of concentration-effect models and pharmacokinetic principles to these haemostatic variables showed that endothelial TFPI release has a maximum that is already reached at low heparin dose, corresponding with an anti-IIa activity of 0.08 IU ml,1. The relationship between anti-IIa activity and TFPI release rate showed signs of acute tolerance (clockwise loop) indicating exhaustion of endothelial TFPI pools. These findings may be of importance for the heparin dose used in conditions such as unstable angina, in which the favourable effects of heparin have been ascribed to its ability to release TFPI. [source] A Practical Method to Estimate the Bed Height of a Fluidized Bed of Fine ParticlesCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 12 2008M. Zhang Abstract Knowledge of both dense bed expansion and freeboard solids inventory are required for the determination of bed height in fluidized beds of fine particles, e.g., Fluidized Catalytic Cracking (FCC) catalysts. A more accurate estimation of the solids inventory in the freeboard is achieved based on a modified model for the freeboard particle concentration profile. Using the experimentally determined dense bed expansion and the modified freeboard model, a more practical method with improved accuracy is provided to determine the bed height both in laboratory and industrial fluidized beds of FCC particles. The bed height in a fluidized bed can exhibit different trends as the superficial gas velocity increases, depending on the different characteristics of the dense bed expansion and solids entrainment in the freeboard. The factors that influence the bed height are discussed, showing the complexity of bed height and demonstrating that it is not realistic to determine the bed height by a generalized model that can accurately predict the dense bed expansion and freeboard solids inventory simultaneously. Moreover, a method to determine the bed height, based on axial pressure fluctuation profiles, is proposed in this study for laboratory fluidized beds, which provides improved accuracy compared to observation alone or determining the turning points in the axial pressure profiles, especially in high-velocity fluidized beds. [source] Addressing Central Nervous System (CNS) Penetration in Drug Discovery: Basics and Implications of the Evolving New ConceptCHEMISTRY & BIODIVERSITY, Issue 11 2009Andreas Reichel Abstract Despite enormous efforts, achieving a safe and efficacious concentration profile in the brain remains one of the big challenges in central nervous system (CNS) drug discovery and development. Although there are multiple reasons, many failures are due to underestimating the complexity of the brain, also in terms of pharmacokinetics (PK). To this day, PK support of CNS drug discovery heavily relies on improving the blood,brain barrier (BBB) permeability in vitro and/or the brain/plasma ratio (Kp) in vivo, even though neither parameter can be reliably linked to pharmacodynamic (PD) and efficacy readouts. While increasing BBB permeability may shorten the onset of drug action, an increase in the total amount in brain may not necessarily increase the relevant drug concentration at the pharmacological target. Since the traditional Kp ratio is based on a crude homogenization of brain tissue, it ignores the compartmentalization of the brain and an increase favors non-specific binding to brain lipids rather than free drug levels. To better link exposure/PK to efficacy/PD and to delineate key parameters, an integrated approach to CNS drug discovery is emerging which distinguishes total from unbound brain concentrations. As the complex nature of the brain requires different compartments to be considered when trying to understand and improve new compounds, several complementary parameters need to be measured in vitro and in vivo, and integrated into a coherent model of brain penetration and distribution. The new paradigm thus concentrates on finding drug candidates with the right balance between free fraction in plasma and brain, and between rate and extent of CNS penetration. Integrating this data into a coherent model of CNS distribution which can be linked to efficacy will allow it to design compounds with an optimal mix in physicochemical, pharmacologic, and pharmacokinetic properties, ultimately mitigating the risk for failures in the clinic. [source] Application of Multivariate curve resolution-alternating least square methods on the resolution of overlapping CE peaks from different separation conditionsELECTROPHORESIS, Issue 20 2007Fang Zhang Abstract Discussed in this paper is the development of a new strategy to improve resolution of overlapping CE peaks by using second-order multivariate curve resolution with alternating least square (second-order MCR-ALS) methods. Several kinds of organic reagents are added, respectively, in buffers and sets of overlapping peaks with different separations are obtained. Augmented matrix is formed by the corresponding matrices of the overlapping peaks and is then analyzed by the second-order MCR-ALS method in order to use all data information to improve the precision of the resolution. Similarity between the resolved unit spectrum and the true one is used to assess the quality of the solutions provided by the above method. 3,4-Dihydropyrimidin-2-one derivatives (DHPOs) are used as model components and mixed artificially in order to obtain overlapping peaks. Three different impurity levels, 100, 20, and 10% relative to the main component, are used. With this strategy, the concentration profiles and spectra of impurities, which are no more than 10% of the main component, can be resolved from the overlapping peaks without pure standards participant in the analysis. The effects of the changes in the components spectra in the buffer with different organic reagents on the resolution are also evaluated, which are slight and can thus be ignored in the analysis. Individual data matrices (two-way data) are also analyzed by using MCR-ALS and heuristic evolving latent projections (HELP) methods and their results are compared with those when MCR-ALS is applied to augmented data matrix (three-way data) analysis. [source] Modeling polycyclic aromatic hydrocarbon composition profiles of sources and receptors in the Pearl River Delta, China,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2008Chang Lang Abstract Changes in concentration profiles of polycyclic aromatic hydrocarbons (PAHs) from emission sources to various environmental media in the Pearl River Delta, China were investigated using fugacity modeling under steady state assumption. Both assumed evenly and observed unevenly distributed PAH moles emission profiles were applied. Applicability of the fugacity model was validated against the observed media PAH concentrations and profiles. At equal emission rates, the differences of media concentrations among various PAHS were as high as three (air) to seven (soil and sediment) orders of magnitude. Dramatic changes of PAH profiles from emission sources to various bulk environmental media also were demonstrated by using the actual emission rates. In general, the fractions of higher molecular weight PAHs in air and water were much lower than those at the emission sources, although the PAH profiles in soil and sediment were characterized by a significant reduction of lower molecular weight PAHs. It is likely that the field-measured median concentration profiles cannot be adopted directly for source apportionment without rectification. The most influential parameters affecting PAH profiles in the study area were emission rates, degradation rates, adsorption coefficient, Henry's law constant, PAH concentrations in upstream surface water, fugacity ratio, vapor pressure, and diffusion coefficient in air. [source] Congener-specific toxicokinetics of polychlorinated dibenzo- p -dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in black-eared kites (Milvus migrans): Cytochrome P4501A,dependent hepatic sequestrationENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2006Akira Kubota Abstract Concentrations of dioxins and related compounds (DRCs), such as polychlorinated dibenzo- p -dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs), were determined in black-eared kites (BEKs; Milvus migrans) collected from the Kanto district in Japan. Total 2,3,7,8-tetra-CDD toxic equivalents (TEQs) were in the range of 99 to 3,800 pg/g lipid weight in the liver and 42 to 760 pg/g lipid weight in the pectoral muscle. Three congeners, including PCB 126, 2,3,4,7,8-penta-CDF, and 1,2,3,7,8-penta-CDD, made a greater contribution to total TEQs in both tissues. Levels of ethoxy-resorufin- O -deethylase activity and a cross-reactive protein with anti-rat cytochrome P4501A (CYP1A) polyclonal antibodies showed no significant correlation with hepatic TEQs. This may be attributed to low sensitivity and insufficient TEQ levels to cause CYP1A induction, high metabolic potential of a series of congeners, and influence of CYP1A inducers other than DRCs. Most of the PCDD/Fs and non- ortho Co-PCBs exhibited a total TEQ- and CYP1A-dependent increase in the liver to muscle concentration ratios, implying their concentration-dependent hepatic sequestration in which CYP1A was involved. Comparison of the toxicokinetics in avian species revealed that BEKs possibly have higher potentials than common cormorants for metabolizing and sequestering certain congeners in the liver in terms of hepatic concentration profiles and liver:muscle concentration ratios, respectively. These results clearly indicate that the toxicokinetics of DRCs is congener-, tissue-, and species-specific as well as concentration-dependent. Therefore, CYP1A expression is one of the critical factors that determine the toxicokinetics in wild avian species. [source] Methodology for the evaluation of cumulative episodic exposure to chemical stressors in aquatic risk assessment,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2000Michael G. Morton Abstract An ecological risk assessment method was developed to evaluate the magnitude, duration, and episodic nature of chemical stressors on aquatic communities. The percent of an ecosystem's species at risk from a designated chemical exposure scenario is generated. In effects assessment, probabilistic extrapolation methods are used to generate estimated safe concentrations (ESCs) for an ecosystem using laboratory toxicity test results. Fate and transport modeling is employed to generate temporal stressor concentration profiles. In risk characterization, area under the curve integration is performed on predicted exposure concentration profiles to calculate a cumulative exposure concentration (CEC) for the exposure event. A correction is made to account for the allowable exposure duration to the stressor ESC. Finally, the CEC is applied to the extrapolation model (curve) of the stressor to predict percent species at risk to the episodic exposure. The method may be used for either prospective or retrospective risk assessments. The results of a retrospective risk assessment performed on the Leadenwah Creek, South Carolina, USA, estuarine community are presented as a case study. The creek experienced periodic episodes of pesticide-contaminated agricultural runoff from 1986 through 1989. Although limited biological data were available for method validation, the risk estimates compared well with the Leadenwah Creek in situ bioassay results. [source] WDX Studies on Ceramic Diffusion Barrier Layers of Metal Supported SOECsFUEL CELLS, Issue 6 2009D. Wiedenmann Abstract Solid oxide electrolyser cells (SOECs) have great potential for efficient and economical production of hydrogen fuel. Element diffusion between the Ni-cermet electrode and the metal substrate of metal supported cells (MSC) is a known problem in fuel cell and electrolysis technology. In order to hinder this unintentional mass transport, different ceramic diffusion barrier layers (DBLs) are included in recent cell design concepts. This paper is based on wavelength dispersive X-ray fluorescence investigations of different SOEC and focuses on Fe, Cr and Ni diffusion between the metal grains of the cathode and the metal substrate. Due to the low detection limits and therefore high analytical sensitivity, wavelength dispersive electron probe microanalysis (EPMA) provides a precise method to determine element distribution, absolute element concentration and changes between the reference material and aged cells on a microstructural level by element mappings and concentration profiles. The results of this work show considerable concentration gradients in the metal grains caused by mass exchange during cell operation. Diffusion can be inhibited significantly by integrating different ceramic DBLs of doped LaCrO3 -type or doped LaMnO3 -type perovskite, either by vacuum plasma spraying (VPS) or physical vapour deposition technique (PVD). [source] A thermochemical boundary layer at the base of Earth's outer core and independent estimate of core heat fluxGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2008David Gubbins SUMMARY Recent seismological observations suggest the existence of a ,150-km-thick density-stratified layer with a P -wave velocity gradient that differs slightly from PREM. Such a structure can only be caused by a compositional gradient, effects of a slurry or temperature being too small and probably the wrong sign. We propose a stably stratified, variable concentration layer on the liquidus. Heat is transported by conduction down the liquidus while the light and heavy components migrate through the layer by a process akin to zone refining, similar to the one originally proposed by Braginsky. The layer remains static in a frame of reference moving upwards with the expanding inner core boundary. We determine the gradient using estimates of co, the concentration in the main body of the outer core, and cb, the concentration of the liquid at the inner core boundary. We determine the depression of the melting point and concentrations using ideal solution theory and seismologically determined density jumps at the inner core boundary. We suppose that co determines ,,mod, the jump from normal mode eigenfrequencies that have long resolution lengths straddling the entire layer, and that cb determines ,,bod, the jump determined from body waves, which have fine resolution. A simple calculation then yields the seismic, temperature, and concentration profiles within the layer. Comparison with the distance to the C-cusp of PKP and normal mode eigenfrequencies constrain the model. We explore a wide range of possible input parameters; many fail to predict sensible seismic properties and heat fluxes. A model with ,,mod= 0.8 gm cc,1, ,,bod= 0.6 gm cc,1, and layer thickness 200 km is consistent with the seismic observations and can power the geodynamo with a reasonable inner core heat flux of ,2 TW and nominal inner core age of ,1 Ga. It is quite remarkable and encouraging that a model based on direct seismic observations and simple chemistry can predict heat fluxes that are comparable with those derived from recent core thermal history calculations. The model also provides plausible explanations of the observed seismic layer and accounts for the discrepancy between estimates of the inner core density jumps derived from body waves and normal modes. [source] Modelling night-time ecosystem respiration by a constrained source optimization methodGLOBAL CHANGE BIOLOGY, Issue 2 2002Chun-Ta Lai Abstract One of the main challenges to quantifying ecosystem carbon budgets is properly quantifying the magnitude of night-time ecosystem respiration. Inverse Lagrangian dispersion analysis provides a promising approach to addressing such a problem when measured mean CO2 concentration profiles and nocturnal velocity statistics are available. An inverse method, termed ,Constrained Source Optimization' or CSO, which couples a localized near-field theory (LNF) of turbulent dispersion to respiratory sources, is developed to estimate seasonal and annual components of ecosystem respiration. A key advantage to the proposed method is that the effects of variable leaf area density on flow statistics are explicitly resolved via higher-order closure principles. In CSO, the source distribution was computed after optimizing key physiological parameters to recover the measured mean concentration profile in a least-square fashion. The proposed method was field-tested using 1 year of 30-min mean CO2 concentration and CO2 flux measurements collected within a 17-year-old (in 1999) even-aged loblolly pine (Pinus taeda L.) stand in central North Carolina. Eddy-covariance flux measurements conditioned on large friction velocity, leaf-level porometry and forest-floor respiration chamber measurements were used to assess the performance of the CSO model. The CSO approach produced reasonable estimates of ecosystem respiration, which permits estimation of ecosystem gross primary production when combined with daytime net ecosystem exchange (NEE) measurements. We employed the CSO approach in modelling annual respiration of above-ground plant components (c. 214 g C m,2 year,1) and forest floor (c. 989 g C m,2 year,1) for estimating gross primary production (c. 1800 g C m,2 year,1) with a NEE of c. 605 g C m,2 year,1 for this pine forest ecosystem. We conclude that the CSO approach can utilise routine CO2 concentration profile measurements to corroborate forest carbon balance estimates from eddy-covariance NEE and chamber-based component flux measurements. [source] | |||||||||||||||||||||||||||||||||||||||||||