Particle Distribution Profiles Research Articles

Numerical simulation of fluid-particle flow of jet in supercritical water environment

Supercritical water gasification provides a new approach to the green transformation of coal. Nevertheless, the flow characteristics of fluids and particles injected into the reactor through the nozzle still need to be further investigated. In this paper, a three-dimensional numerical simulation of the particle jet in supercritical water environment is carried out coupling Large Eddy Simulation (LES) with Discrete Phase Model (DPM). The simulation focuses on the effects of particle size, Stokes number, mass flux ratio and initial fluid velocity on the flow characteristic of the fluid-particle flow, especially on the vortex structure evolution, particle distribution and velocity profile. The findings are that as the particle size decreases and the initial fluid velocity increases, the evolution of vortex structures become increasingly fierce, such as the destruction of large-scale coherent structures, the disappearance of vortex ribs, and the lateral expansion of vortices in the development section. Particle distribution exhibits characteristics similar to the vortex structure, as particles adhere closely to the carrier fluid at low Stokes number (St < 1). On the contrary, with increasing of Stokes number (St > 1), the particles are freer from fluid interference and keep their original motion state moving forward. The fluid velocity at the center of the transverse interface jet decrease with increased mass flow ratio. For higher initial fluid velocities, particle distribution is more uniform, and more particles are carried to areas with larger radial distances.

Generalized Harris Sheet Equilibrium in Regularized Kappa Distributed Plasmas

Harris sheet models with antiparallel magnetic field are the equilibrium solutions to the steady Vlasov–Maxwell equations, which have been widely adopted for the study of plasma instabilities and magnetic reconnection in thin current sheets. The original Harris equilibrium model assumes the Maxwellian velocity distribution, which necessarily gives rise to the isothermal current sheets. Many observations have shown that the suprathermal populations are indispensable features of particle distribution profiles, which may well be fitted by the Kappa distribution (KD) functions with the free parameter κ. The Harris equilibrium based on the standard Kappa distribution (SKD), however, may become unphysical for . Alternatively, the regularized KD (RKD) with two adjustable parameters, κ and α 2, has been proposed to replace the SKD in various studies. The RKD may recover the SKD for α 2 = 0, and Maxwellian model for α 2 = 0 and κ → ∞ . This paper presents the first results of adopting the nonthermal RKDs in the Harris equilibrium models. It is shown that the new RKD–Harris equilibrium is applicable for all κ values, and exhibits a stronger magnetic field associated with higher temperature in the asymptotic region. The proposed formulations for the generalized Harris sheet equilibrium may be applied to multiple component plasmas (e.g., electrons, protons) with different RKDs and temperatures.

Totally asymmetric simple exclusion process with particle annihilation

The cargo transport in biological cells often happens under a crowded environment. Past experiments have revealed that cargoes have the ability to self-assemble by associating or dissociating multiple motor proteins, which can impede the forward motion of cargoes on biopolymeric tracks. Motivated by these processes, we study a totally asymmetric simple exclusion process with possibilities of annihilation of particles. The model consists of a one-dimensional track on which two species of particles, one carrying cargoes and the other representing free motor proteins, hop obeying the exclusion principle. Further, the cargo carrying particle can annihilate the other species of particles occupying the forward site at a rate r a . The annihilation process causing particle non-conservation leads to a nonlinear coupling between the two species of particles. We show that this system undergoes boundary induced phase transitions in the state. Using the method of boundary-layer analysis, we find mean-field solutions for the average particle distribution profile across the lattice in the steady state. Analyzing these solutions and the phase portrait of the boundary-layer differential equation, we predict the phase diagram, which consists of a low-density, a high-density and a shock phase. We find that the shapes of the density profiles are affected differently in different phases by the annihilation process. The shapes of the density profiles in different phases agree qualitatively with results from numerical simulations.

Particle-in-cell simulation of an industrial magnetron with electron population analysis

Results from a particle-in-cell simulation study of L3Harris CWM-75 kW are presented; the continuous wave cooker magnetron typically operates at 18 kV, 5 A, 1900 G, 896–929 MHz. The startup process of the device has been simulated in 3D by using the PIC code VSim. The startup behavior was examined with (1) no priming, (2) RF priming, and (3) cathode modulation. Under no priming, the simulated device failed to oscillate in a simulation time of 1000 ns. Oscillations were achieved with both RF priming (150 ns) and cathode modulation (180 ns). Half (∼40 kW) of the device’s typical operating power at a frequency of 915 MHz, the device’s π-mode frequency, was used for the RF priming, and the priming was active only during the first 50 ns of the simulation. The device then oscillated later, but oscillation soon failed as the spokes collapsed. Continuous cathode modulation was also performed at 915 MHz with stable oscillation after 180 ns. A method for analyzing the electron device physics during the magnetron startup was developed by examining time-dependent particle distribution profiles in r and φ. These results provide insight into the conditions in the electron hub that lead to oscillation, particularly the azimuthal velocity distribution where the distribution shows a clear low or negative velocity prior to the start of oscillation.

Improved oral delivery of tilianin through lipid–polymer hybrid nanoparticles to enhance bioavailability

Tilianin (TIL) may prevent and treat myocardial ischemia reperfusion injuries. However, its oral administration is hampered by its low bioavailability. The present study aimed to formulate lipid–polymer hybrid nanoparticles (LPHNs) as carriers for the sustained release and oral bioavailability enhancement of TIL in vitro and in vivo. A nanodrug delivery system of TIL-loaded LPHNs (TIL-LPHNs) was constructed. TIL-LPHNs were prepared via a self-assembly method, and their particle size, polymer dispersity index (PDI), zeta potential, encapsulation efficiency (EE) and morphology were investigated. In addition, pharmacokinetic studies were performed in vivo. The TIL-LPHN formulation produced a spherical, homogeneous, smooth surface and multi-lamellar structured nanoparticles. The particle size and distribution profile of TIL-LPHNs had a mean particle diameter of 54.6 ± 5.3 nm and PDI of 0.112 ± 0.017. The zeta potential was −33.4 ± 4.7 mV. The EE of TIL-LPHNs was 86.6 ± 3.6%, which was determined with the dialysis method. The TIL-LPHNs significantly enhanced the oral bioavailability of TIL with a 3.7-fold increase in the area under the concentration−time curve in comparison with the TIL solution. These findings support the potential use of LPHNs in improving the stability and bioavailability of TIL via oral administration.

Two-way interaction between switching arc and solid surfaces: distribution of ablated contact and nozzle materials

This paper is devoted to two-way plasma-surface interactions by investigating how the plasma arc ablates the nozzle and contacts and how the distribution of ablated materials changes the plasma parameters.For this purpose, a two-dimensional time-dependent model, in axial symmetric coordinates, for an arc at atmospheric pressure burning within a polytetrafluoroethylene nozzle is created. A computational fluid dynamics equations system is solved for plasma velocity, pressure, temperature, magnetic vector potential, and electrical potential. Radiation is modeled based on net emission coefficient and contacts, and nozzle ablation is also considered to better describe the arc formation, contact cooling, and arc temperatures, more precisely. The sublimated materials from contacts and nozzle will be used to calculate the distribution of plasma composition (i.e. ablated mixture ratio). The calculated ratio is used to change the plasma parameters, and data processing techniques are utilized to derive particle distribution and temperature profiles of the arc to investigate its thermo-electrical behavior. The simulation results show good agreement with the measurements obtained in an experimental setup already designed and published. This study provides support to the experimental work and contrariwise. The presence of ablated points on nozzle and contacts, which further modify plasma parameters and therefore the arc voltage are discussed.

On the pressure-driven flow of suspensions: Particle migration in apparent yield-stress fluids

Suspensions of particles with viscoplastic characteristics are often found both in nature and industrial applications. However, in contrast with the case of suspensions in Newtonian fluids, the dynamics of shear-induced particle migration in yield-stress suspending materials is not yet fully understood. In this work, we present a numerical study of particle migration in pressure-driven, tube flows of suspensions of non-colloidal, spherical particles dispersed in apparent yield-stress fluids. The suspension viscosity is modeled using the classical Krieger–Dougherty equation with a novel regularized viscosity function for viscoplastic materials as the suspending medium viscosity, and the dynamics of shear-induced particle migration is described with the Diffusive Flux Model. The resulting fully coupled, non-linear, one-dimensional model is solved with a second-order finite difference scheme coupled with Newton’s method. We present a parametric study that elucidates the role played by the suspension bulk concentration, Plastic number, and power-law index on the velocity profile and particle concentration distribution in the flow. Remarkably, the results show that particle migration in apparent yield-stress fluids leads to a strikingly different pattern of velocity and particle distribution profiles relative to the case of suspensions in Newtonian liquids and true yield-stress materials.

Pressure and particle property impacts on radiation in oxy-coal combustion

A numerical study evaluating the significance of scattering phase function, particle size, particle distribution and pressure in an oxy-coal combustor was conducted. Particle absorption and scattering coefficients were calculated from particle properties and Mie theory. Mie theory was also used to identify appropriate scattering phase functions as a function of particle size. A strongly forward scattering function represented by a Henyey-Greenstein function was found to match scattering behavior for particle diameters greater than approximately 10 μm. A comparison of highly forward scattering based on two mono-sized particle distributions (15 µm and 119 µm) and a polydisperse size distribution (27.9 µm SMD) showed small particles produced peak incident wall heat fluxes 30–40% greater than large particles due to the increased number density with the smaller particles. The polydisperse distribution produced flux profiles similar but slightly higher than the 15 µm mono-sized particles. Although strongly forward scattering was found to best represent particle scattering for this system, data did suggest that phase function/scattering coefficient influence becomes more important with increasingly small particle size. Two particle distribution profiles (narrow and wide) were used to represent different coal flame profiles. A wide particle distribution across the combustor diameter produced higher incident wall heat fluxes than a narrow distribution limited to the center region of the combustor. Increased particle size decreased the effect of distribution. Incident wall heat flux was found to increase with increasing combustor pressure up to approximately 5 atm and 10 atm, respectively, for wide and narrow particle distributions. This was primarily due to increased particle absorption and scattering coefficients. Additional pressure increases beyond this up to 20 atm had minimal impact on wall fluxes due to saturated values of the particle absorption coefficient.

Characterization of solid–liquid settling suspensions using Electrical Impedance Tomography: A comparison between numerical, experimental and visual information

To address the limitation of traditional characterization techniques, over the past two decades, non-invasive monitoring tomography techniques have been employed in the study of multiphase systems. Amongst them, electrical tomography offers several advantages when compared with the traditional methods, such as providing information on the boundaries between mixture components, flow regimes, concentration distribution in the cross section of conveying pipes and mixing zones distribution in stirred tanks, amongst others, resulting in a better understanding of the monitored process and as a means of validating physical models.With the present study the objective was to validate experimental particle distribution profiles attained with an EIT apparatus, for two different average particle sizes, 0.15 and 0.5mm, and increasing volumetric concentration up until 11.0% (v/v), in a horizontal flow pipe cross section. To this end, experimental particle distribution profiles from a Sampling Probe (SP), numerical particle distribution profiles obtained using the Mixture Model coupled with a High Reynolds k–ɛ turbulence model and visual inspection served as a comparison basis (Goeree et al., 2016; Silva et al., 2015). Analysis of the resulting 1D particle distribution profiles from both experimental techniques and numerical data shows a good agreement, thus, demonstrating the potential of the EIT in the characterization of solid–liquid suspensions flow for the range of particle concentrations and sizes tested.

Effect of surface ligand density on cytotoxicity and pharmacokinetic profile of docetaxel loaded liposomes

Various biotin-modified liposomes incorporated with docetaxel (DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome (PDL), 0.5% (mol) biotin modified liposome (0.5BDL), 1% (mol) biotin modified liposome (1BDL) and 2% (mol) biotin modified liposome (2BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency (EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.

Characterization of Submicron (0.1–1 μm) Particles in Therapeutic Proteins by Nanoparticle Tracking Analysis

The importance of 0.1-1 μm submicron particles characterization in therapeutic proteins, which was limited because of a lack of suitable methods, has been recognized recently. An application of nanoparticle tracking analysis (NTA) for characterization of 18 lots of recombinant fusion protein (rP1) drug product presentation along with stressed samples of this material exposed to heat at 50°C, agitation, and UV light was studied. In addition, monodisperse polystyrene standards with nominal sizes of 60-800 nm and rP1 samples spiked with 100-400 nm polystyrene standards were analyzed. The NTA technique was capable of demonstrating good sizing of monodisperse polystyrene standards, detect small particle size population in 800 nm standard, and resolve three size populations in the mixture of four standards (60-400 nm). The NTA was also capable of resolving 400 nm polystyrene standard from the main rP1 peak, but was not able to resolve 100 and 200 um standards because of the particle distribution profiles overlap. A characterization of 0.1-1 μm submicron particles in rP1 showed a relatively diverse range of mean particle diameters, D90, and size distributions, which was not linked to the lots storage duration prior to analysis. The size distribution profile of rP1was specific for a single lot and did not show significant variability, which allowed detection of larger particle population in stressed samples compared with a control. Overall, the NTA technique is suitable for characterization of submicron particles in a studied therapeutic protein. However, the NTA can only be used as a semiquantitative methodology, because frequent sample dilution is required to achieve optimal particle concentration.

Modeling of particle–resin suspension impregnation in compression resin transfer molding of particle-filled, continuous fiber reinforced composites

A particle–resin suspension impregnation model is used for analyzing the mold filling process in compression resin transfer molding (CRTM) of particle-filled, continuous fiber composites. The model is based on Darcy flow coupled with particle filtration and is applicable to two-dimensional impregnation through isotropic/anisotropic fiber preforms. Comparisons with simple analytical solutions and experimental results from the literature were made to validate the numerical solution. Simulations showed that CRTM was advantageous over resin transfer molding (RTM) for smaller non-homogeneity in composite microstructure, when particle filtration was high. Limits on certain process parameters were observed beyond which molding pressures in CRTM became comparable with those in RTM. The preform anisotropy was effective in the particle distribution profile. The choice of inlet gate configuration in CRTM was found influential in the particle distribution homogeneity and molding pressures. The developed modeling tool can be extended to analyze any composite liquid molding process involving particle fillers.

Comparing MDI and DPI Aerosol Deposition Using In Vitro Experiments and a New Stochastic Individual Path (SIP) Model of the Conducting Airways

Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles. In vitro experiments were used to determine initial particle distribution profiles and to validate computational fluid dynamics (CFD) model results for a MDI and DPI delivering the same dose of drug in a geometry of the mouth-throat and tracheobronchial airways. The validated CFD model was then used to predict the transport and deposition of the drug using correct and incorrect inhalation profiles for each inhaler. The MDI delivered approximately two times more drug to the tracheobronchial region compared with the DPI for both correct and incorrect inhalation profiles. Errors in inhalation reduced the deposited tracheobronchial dose by approximately 30% for both inhalers. The DPI delivered the largest dose to the mouth-throat (~70%) and the MDI delivered the largest dose to the alveolar airways (~50%). The developed in silico model provides new insights into the lung delivery of pharmaceutical aerosols and can be applied in future studies in combination with pharmacokinetic analysis to establish bioequivalence between devices.

Effects of relative humidity and substrate on the spatial association between glyphosate and ethoxylated seed oil adjuvants in the dried deposits of sessile droplets

In recent years, several studies have shown the impact of adjuvants on the characteristics of herbicide deposits on leaf surfaces. Until now, most studies have addressed the distribution of active ingredients (AIs), whereas few experiments have focused on the location of the adjuvants. The objective of this study was a systematic examination of the particle distribution profile of both the AI (glyphosate, Gly) and the adjuvants after the application of sessile microdroplets on hydrophobic (Teflon) and hydrophilic (glass and aluminium) model surfaces. The association degree (AD) was surface dependent and specific for the tested adjuvants. In general, the rather hydrophobic adjuvant RSO 5 showed decreasing AD with Gly at increasing relative humidity (RH) levels. The rather hydrophilic RSO 60 adjuvant displayed higher AD between the compounds at a higher RH. A high concentration of the adjuvant reduced the AD for both of the RSO adjuvants evaluated. The combination of surface properties, the type of adjuvant and the relative humidity determines the degree of association between Gly and the adjuvants. The present results suggest that the interaction between the AI and an adjuvant determines whether spatial separation occurs, whereas physical processes (e.g. capillary particle movement, inward and outward Marangoni flows and the evaporation rate) are decisive for the extent of the separation. Coffee-ring structures were formed exclusively with the adjuvant+Gly mixtures, whereas Gly alone formed either one big deposit or several small islands distributed within the droplet footprint.

Three-dimensional simulation of the particle distribution in a downer using CFD–DEM and comparison with the results of ECT experiments

A three-dimensional numerical model of the down-flow fluidized bed (Downer) with a newly designed distributor was applied to investigate the particle distribution profiles using combined computational fluid dynamics (CFD) and the discrete element method (DEM). A realistic model of DEM, which calculates the contact force acting on the individual particles, is used to monitor the movement of individual particles in the bed. The contact force is calculated using the concepts of the spring, dash-pot, and friction slider. The flow field of gas is predicted by the Navier–Stokes equation. This CFD–DEM model provides information regarding the particle movement and distribution, the particle velocity, and the gas velocity in the bed under different air-particle mixture conditions. The results demonstrate that the air supply conditions directly influence the particle distribution uniformity. Furthermore, the numerical predictions for the axial and radial profiles of the particle distribution were found to agree well with the experimental results obtained by electrical capacitance tomography (ECT).

Organocopper complexes during roxarsone degradation in wastewater lagoons

Organoarsenical-containing animal feeds that promote growth and resistance to parasites are mostly excreted unchanged, ending up in nearby wastewater storage lagoons. Earlier work documented the partial transformation of organoarsenicals, such as, 3-nitro-4-hydroxyphenylarsonic acid (roxarsone) to the more toxic inorganic arsenate [As(V)] and 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA). Unidentified roxarsone metabolites using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC/ICP-MS) were also inferred from the corresponding As mass balance. Earlier batch experiments in our laboratory suggested the presence of organometallic (Cu) complexes during relevant roxarsone degradation experiments. We hypothesized that organocopper compounds were complexed to roxarsone, mediating its degradation in field-collected swine wastewater samples from storage lagoons. The objective of this study was to investigate the role of organometallic (Cu) complexes during roxarsone degradation under aerobic conditions in swine wastewater suspensions, using electrospray ionization mass spectrometry (ES-MS). Two swine wastewater samples differing in % solids content and total recoverable Cu concentrations were reacted with 500 ppb of roxarsone under aerobic conditions for 16 days. LC/ICP-MS and ES-MS were used for As speciation analyses, and characterization of metal-organoarsenical complexes in swine wastewater subsamples, respectively. An organocopper roxarsone metabolite was found only in the high-Cu wastewater sample, suggesting the role of Cu in roxarsone degradation under aerobic conditions. The organocopper metabolite was not found in the low-Cu wastewater sample, because roxarsone did not undergo degradation under aerobic conditions even after 16 days. Aerobic degradation of organoarsenicals (roxarsone) has not been documented before. Preliminary dataset from this study illustrates the direct and/or indirect association of particulate Cu in catalyzing roxarsone degradation under aerobic conditions in samples with high % solids content. Concerns regarding the degradation of roxarsone in wastewater to the more toxic inorganic As may be partially linked to the presence of particulate Cu. The presence of Cu in wastewater-suspended particle surfaces has never been coupled before to organoarsenicals degradation reactions, thus, further studies are needed to elucidate the related reaction mechanisms and pathways. Water depth-dependent solid particle distribution profiles in wastewater storage lagoons could provide empirical evidence towards the design of effective degradation practices for nitrophenol-containing compounds, such as, organoarsenical-containing antibiotics, or explosive munitions compounds.

Encapsulation of cyclodextrin complexed simvastatin in chitosan nanocarriers: A novel technique for oral delivery

The purpose of the present work was to design and investigate the potential of novel hydroxylpropyl-beta-cyclodextrin (HP-β-CD) and chitosan nanocarriers (NCs) for effective delivery of model, poorly water soluble drug simvastatin. The prepared system was characterized for particle size, particle size distribution (PDI), zeta potential, differential scanning calorimetery, x-ray diffraction, encapsulation efficiency and drug release studies. The results revealed that among the selected ratios of tripolyphosphate/chitosan, ratio 1:4 and 1:5 proved to be optimum in terms of particle size, particle distribution and drug release profile. The average size of nanoparticles increased from 516 to 617 and 464 to 562 nm for ratio 1:4 and 1:5 with increase in drug/HP-β-CD amount. To assess interactions and whether the simvastatin was incorporated in the NCs in its crystalline or amorphous form DSC and XRD were performed. These results suggest that the encapsulation process produces a marked decrease in crystallinity of simvastatin and/or confers to a nearly amorphous state of drug in NCs. Results reveled that with increase in the amount of HP-β-CD/drug the final loading of the NCs increased due to increased solubilization of simvastatin in the presence of HP-β-CD. The in vitro release profile of prepared NCs showed initial fast release (burst effect) followed by a delayed release pattern. In conclusion, these nanocarriers constitute a novel and efficient system for encapsulation and oral delivery of poorly soluble drugs.

Effects of Rice Flour Properties on Specific Loaf Volume of One-loaf Bread Made from Rice Flour with Wheat Vital Gluten

Using various rice flours prepared by different milling methods, the relationship between rice flour properties and specific loaf volumes of one-loaf bread made from rice flour with wheat vital gluten were studied. Damaged starch content of rice flour varied from 1.0% to 22.1%. A significant negative correlation was verified between damaged starch content and specific loaf volume of one-loaf bread. Rice flour with low damaged starch content mainly consisted of compound starch granules, aggregated polyhedral single starch granules and smooth surface cells surrounded by the cell wall. The structures of starch granules and cells were maintained in rice flour with low damaged starch content. Rice flour with high damaged starch content consisted of only fine irregular particles without the apparent rice starch structure, or contained fractured large and small cells with rough surface. Although there was not significant correlation between specific loaf volume and median particle size, rice flours which were successful at making bread with high specific loaf volume commonly showed a peak centered around 60 µm with a smaller amount of larger size particles in the particle distribution profile. Thus, the flour particle size distribution appears to affect the specific loaf volume of one-loaf bread. Both the damaged starch content and the profile of particle size distribution were important for high specific loaf volume of one-loaf bread. Less damage to starch and cell structures while lowering the particle size during milling process is critical in obtaining better flour for rice one-loaf bread making.

VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe/simvastatin and fenofibrate

This analysis evaluates the effects on lipoprotein subfractions and LDL particle size of ezetimibe/simvastatin with or without coadministration of fenofibrate in patients with mixed hyperlipidemia. This multicenter, double-blind, placebo-controlled, parallel-group study included 611 patients aged 18-79 years randomized in 1:3:3:3 ratios to one of four 12 week treatment groups: placebo; ezetimibe/simvastatin 10/20 mg/day; fenofibrate 160 mg/day; or ezetimibe/simvastatin 10/20 mg/day + fenofibrate 160 mg/day. At baseline and study endpoint, cholesterol associated with VLDL, intermediate density lipoprotein (IDL), LDL, and HDL subfractions was quantified using the Vertical Auto Profile II method. LDL particle size was determined using segmented gradient gel electrophoresis. Whereas fenofibrate reduced cholesterol mass within VLDL and IDL, and shifted cholesterol from dense LDL subfractions into the more buoyant subfractions and HDL, ezetimibe/simvastatin reduced cholesterol mass within all apolipoprotein B-containing particles without significantly shifting the LDL particle distribution profile. When administered in combination, the effects of the drugs were complementary, with more-pronounced reductions in VLDL, IDL, and LDL, preferential loss of more-dense LDL subfractions, and increased HDL, although the effects on most lipoprotein subfractions were not additive. Thus, ezetimibe/simvastatin + fenofibrate produced favorable effects on atherogenic lipoprotein subclasses in patients with mixed hyperlipidemia.

Effects of fenofibrate and ezetimibe, both as monotherapy and in coadministration, on cholesterol mass within lipoprotein subfractions and low-density lipoprotein peak particle size in patients with mixed hyperlipidemia

Coadministration of fenofibrate and ezetimibe (FENO + EZE) produced complementary and favorable effects on the major lipids and lipoproteins, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C), and non–HDL-C levels, and was well tolerated in patients with mixed hyperlipidemia. The current analysis evaluates the effects of FENO and EZE, as monotherapies and in coadministration, on lipoprotein subfractions and LDL particle size distributions in these patients. In a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients with mixed hyperlipidemia were randomized in a 1:3:3:3 ratio to one of 4 treatment groups: placebo, FENO 160 mg/day, EZE 10 mg/day, or FENO 160 mg/day + EZE 10 mg/day. At baseline and study end point, the Vertical Auto Profile II method was used to measure the cholesterol associated with 2 very low-density lipoprotein (VLDL) subfractions (VLDL-C1 + 2 and VLDL-C3), intermediate-density lipoproteins (IDL-C), and 4 LDL subfractions (LDL-C1 through LDL-C4, from most buoyant to most dense), lipoprotein (Lp) (a), and 2 HDL-C subfractions (HDL-C2 and HDL-C3). The LDL particle size was determined using segmented gradient gel electrophoresis. Fenofibrate reduced cholesterol mass within VLDL, IDL, and dense LDL (primarily LDL-C4) subfractions, and increased cholesterol mass within the more buoyant LDL-C2 subfraction, consistent with a shift to a more buoyant LDL peak particle size. Ezetimibe reduced cholesterol mass within all of the apolipoprotein B–containing particles (eg, VLDL-C, IDL-C, and LDL-C) but did not lead to a shift in the LDL particle size distribution profile. Coadministration of FENO and EZE promoted more pronounced reductions in VLDL-C, IDL-C, and LDL-C, and a preferential decrease in dense LDL subfractions. Fenofibrate and FENO + EZE promoted similar increases in HDL-C2 and HDL-C3. Coadministration of FENO + EZE produced complementary and favorable changes in lipoprotein fractions and subfractions, as assessed by the Vertical Auto Profile II method, in patients with mixed hyperlipidemia. These changes reflected the combined effects of FENO in reducing triglycerides-rich lipoproteins and promoting a shift in the LDL particle distribution profile toward larger, more buoyant particles and of EZE in promoting reductions in cholesterol mass across the apolipoprotein B particle spectrum.