Absorption Rate Constant Research Articles

Population Pharmacokinetics of Ensitrelvir in Healthy Participants and Participants with SARS-CoV-2 Infection in the SCORPIO-SR Study.

Ensitrelvir, a novel oral inhibitor of the 3C-like protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has shown efficacy and safety in participants with mild to moderate coronavirus disease 2019 (COVID-19) with once-daily multiple doses of 375mg on day 1 followed by 125mg on days 2-5. The aims of this study were to characterize the pharmacokinetics of ensitrelvir and to explore its exposure-response relationships on the dose regimen. Pharmacokinetic data, including 8034 plasma concentration datasets from 2060 participants, from two phase I and one phase II/III study in healthy participants and participants infected with SARS-CoV-2 were used to develop a population pharmacokinetic model. The correlation between exposure and drug response was evaluated using observed plasma concentrations and estimated pharmacokinetic parameters as pharmacokinetic indexes and viral RNA as drug response. A two-compartment model with a first-order absorption model effectively described plasma ensitrelvir concentrations. The effects of body weight on clearance and volume of distribution and of food conditions and formulation on the absorption rate constant were selected as significant covariates. The efficacy indexes changed in the active group, but the responses were similar across the exposure range in the phase II/III study (SCORPIO-SR) regardless of the effects of the pharmacokinetic covariates. Population pharmacokinetics revealed that body weight is the most important covariate in the pharmacokinetics of ensitrelvir. The antiviral effect, independent of ensitrelvir exposure, was demonstrated on the current dose regimen for treatment of SARS-CoV-2 infection.

Pharmacokinetics of Enteral Lormetazepam in Mechanically Ventilated ICU Patients with COVID-19: An Adjunct Sedative Study.

During the coronavirus disease 2019 (COVID-19) pandemic, sedative prescriptions surged, leading to shortages of midazolam. This study investigates lormetazepam as an adjunct sedative alternative to midazolam for mechanically ventilated patients with COVID-19. We aimed to determine the clinical pharmacokinetics (PK) of enterally administered lormetazepam and provide dosing recommendations. Critically ill patients with acute respiratory distress syndrome (ARDS) or COVID-19 requiring mechanical ventilation were enrolled in April 2020. Lormetazepam 2 mg every 12 h was administered enterally. Blood samples were collected to quantify lormetazepam and its glucuronide. PK analysis was conducted using a one-compartment model with the Edsim++ KinPop plugin. The primary PK parameters (means ± coefficient of variation [CV] %) for absorption constant (Ka), volume of distribution (Vd/F), and clearance (CL/F) were 6.4 h-1, 207 L/70 kg, and 14.5 L/h/kg0.75, respectively. Vd/F and CL/F median values were 2.64 L/kg and 2.53 mL/kg/min, respectively, with a half-life of 10.7 h. Lormetazepam's median ratio to its glucuronide was 11.5. Trough-guided dosing suggested alternatives of 0.92 mg three times daily, 1.62 mg twice daily, or 5.36 mg once daily. This is the first study to report a validated PK model for enterally administered lormetazepam as a sedative adjunct in critically ill adults on mechanical ventilation for ARDS and COVID-19. The model was internally validated using a bootstrap procedure. Adequate lormetazepam concentrations were achieved at prescribed doses, with no significant alterations in clearance or half-life. This population model may aid in dose optimization and sedation management for future intensive care unit (ICU) patients.

FDA and EMA Oversight of Disruptive Science on Application of Finite Absorption Time (F.A.T.) Concept in Oral Drug Absorption: Time for Scientific and Regulatory Changes.

Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug's gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time (F.A.T.) concept and the relevant physiologically based finite-time pharmacokinetic (PBFTPK) models developed provided a better physiologically sound description of oral drug absorption. Methods: In this study, we re-analyzed, using PBFTPK models, seven data sets of ketoprofen, amplodipine, theophylline (three formulations), and two formulations (reference, test) from a levonorgestrel bioequivalence study. Equations for one-compartment-model drugs, for the estimation of fraction of dose absorbed or the bioavailable fraction exclusively from oral data, were developed. Results: In all cases, meaningful estimates for (i) the number of absorption stages, namely, one for ketoprofen and the levonorgestrel formulations, two for amlodipine, the immediate-release theophylline formulation, and the extended-release Theotrim formulation, and three for the extended-release Theodur formulation, (ii) the duration of each absorption stage and the corresponding drug input rate, and (iii) the total duration of drug absorption, which ranged from 0.75 h (ketoprofen) to 11.6 h for Theodur were derived. Estimates for the bioavailable fraction of ketoprofen and two theophylline formulations exhibiting one-compartment-model kinetics were derived. Conclusions: This study provides insights into the detailed characteristics of oral drug absorption. The use of PBFTPK models in drug absorption analysis can be leveraged as a computational framework to discontinue the perpetuation of the mathematical fallacy of classical pharmacokinetic analysis based on the absorption rate constant as well as in the physiologically based pharmacokinetic (PBPK) studies and pharmacometrics. The present study is an additional piece of evidence for the scientific and regulatory changes required to be implemented by the regulatory agencies in the not-too-distant future.

Population pharmacokinetic modeling of zavegepant, a calcitonin gene-related peptide receptor antagonist, in healthy adults and patients with migraine.

Zavegepant (ZAVZPRET™) is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist available for acute treatment of migraine in adults. A population pharmacokinetic analysis was performed to describe zavegepant plasma concentration-time course, characterize bioavailability, and identify covariates affecting zavegepant exposure. The model was developed and validated using data from 10 phase I clinical studies, wherein zavegepant was administered intravenously, intranasally, or orally to healthy adults and patients with migraine. Plasma concentration-time data were analyzed using nonlinear mixed-effects modeling. A three-compartment model with first-order elimination from the central compartment, and sequential zero- and first-order absorption best described the observed plasma concentration-time course of zavegepant. Bioavailability was 5.1% and 0.65% for intranasal and oral treatment, respectively; absorption rate constants were 5.8 and 0.8 h-1, respectively. Body weight-based empirical allometric scaling was applied using standard exponents (0.75 for clearance and 1 for volume of distribution). Age (range 18-71 years), race, ethnicity, sex, renal function, and co-administration of oral contraceptives or sumatriptan did not significantly change zavegepant pharmacokinetics. Moderate hepatic impairment (Child-Pugh score 7-9) or co-administration of rifampin decreased elimination clearance of oral zavegepant by ~40%. The zavegepant population pharmacokinetic model adequately characterized zavegepant concentration-time profiles, the bioavailability of intranasal and oral zavegepant, as well as the effect of intrinsic and extrinsic factors on zavegepant pharmacokinetics.

A microfluidic in vitro method predicting the fate of peptide drugs after subcutaneous administration

For many biopharmaceuticals, subcutaneous (sc) administration is the only viable route. However, there is no in vitro method available accurately predicting the absorption profiles of subcutaneously injected pharmaceuticals. In this work, we show that a recently developed microfluidics method for interaction studies (MIS) has the potential to be useful in this respect. The method utilises the responsiveness of polyelectrolyte microgel networks to oppositely charged molecules as a means to monitor the interaction between peptides and hyaluronic acid (HA), a major constituent of the subcutaneous extracellular matrix. We use the method to determine parameters describing the strength of interaction between peptide and HA as well as the peptide’s aggregation tendency and transport properties in HA networks. The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and in vivo absorption and bioavailability data from the literature. We show that both MIS and SCISSOR reveal differences in the peptides’ diffusivity and tendency to aggregate in the presence of HA. We show that MIS is particularly good at discriminating between peptides forming aggregates stabilised by non-electrostatic forces in the presence of HA, and peptides forming complexes stabilised by electrostatic interactions with HA. The method provides two parameters that can be used to quantify the peptides’ aggregation tendency, the one describing the peptide packing density in complexes with HA and the other the apparent diffusivity upon release in a medium of physiological ionic strength and pH. The order of the peptides when ranked by increasing binding strength at pH 7.4 determined with MIS is shown to be in agreement with the order when ranked by the apparent 1st order absorption rate constant (ka) after sc administration in humans: lanreotide (Autogel) < exenatide (IRF) < AZD2820 < pramlintide < lanreotide (IRF) (IRF: Immediate release formulation). A correlation is found between the 1st order release rate constant determined with SCISSOR and ka for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of ka to the peptides’ charge is proposed.

Population pharmacokinetics of cabotegravir following intramuscular thigh injections in adults with and without HIV.

Cabotegravir intramuscular gluteal injection is approved for HIV treatment (with rilpivirine) and prevention. Thigh muscle is a potential alternative injection site. We aim to characterize cabotegravir pharmacokinetics and its association with demographics following intramuscular thigh injection in comparison with gluteal injection using population pharmacokinetic (PPK) analysis. Fourteen HIV-negative participants received 600 mg single thigh injection in phase 1 study 208832 and 118 participants with HIV received thigh injections 400 mg monthly 4× or 600 mg once-every-2-months 2× after ≥3 years of gluteal injections in phase 3b study ATLAS-2M provided 1,249 cabotegravir concentrations from 366 thigh injections and 1,998 concentrations from 1,618 gluteal injections. The established gluteal PPK model was modified by adding thigh injection compartment and fit to pharmacokinetic data following both gluteal and thigh injections, enabling within-person comparison in ATLAS-2M. Gluteal parameters were fixed. Similar to the gluteal absorption rate constant (KAgluteal), the thigh absorption rate constant (KAthigh) was slower in females than males and in participants with higher BMI. KAthigh was strongly correlated with KAgluteal (correlation coefficient 0.766), best described by the additive linear relationship KAthigh = KAgluteal + 0.0002527 h-1. Terminal half-life of thigh injection was 26% (male) and 39% (female) shorter than gluteal injection. Relative bioavailability of thigh to gluteal was estimated to be 89.9%. The impact of covariates on cabotegravir exposure following thigh injections was ≤35%. In conclusion, cabotegravir absorption following thigh injection was correlated with, faster than, and 10% less bioavailable than gluteal injection, and correlated with sex and BMI. The cabotegravir thigh PPK model can inform dosing strategies and future study design.

Diode Laser Irradiation Effects on Physical Properties of Titanium Dioxide Nano Fillers Doped Polyvinyl Alcohol Films

Study effect of diode laser (wavelength 650 nm) irradiation for different irradiant times (0.25, 0.5, 1.00, 3.00, and 4.00 hrs) on the physical properties of titanium dioxide (TiO2) possess particle size of 15.7 nm doped polyvinyl alcohol (PVA) films were experimentally investigated. The solution casting process has been utilized to create as-prepared TiO2/PVA nanocomposite films. Ultraviolet-Visible (UV-Vis) spectroscopy investigates the samples' optical characteristics by analyzing optical absorption spectra in a wavelength range of (200 - 900 nm) at room temperature (RT) of 300 K. The PVA matrix could be used to describe the influence. All optical constants produced artificially through laser radiation, like absorption, refraction index, extinction coefficient and complex dielectric constants, have decreased with increasing radiation times. On the contrary of optical energy gap they increased with increasing radiation times, according to the study's findings. TiO2 Nanoparticles (NPs) additions significantly impacted the PVA host's optical characteristics. When FTIR-spectrum regarding the TiO2/PVA nanocomposite films was examined in various ratios of irradiation times, the peak positions or bonds did not change; instead, they became smaller or larger as the irradiation time increased.

Two‐Dimensional Solidification Simulation of PCM Molten Salt as a Thermal Energy Storage for Stirling Engine

ABSTRACTThermal energy storage technologies have been widely used to mitigate intermittency from renewable energy sources such as solar energy. Phase change material (PCM) is a material that can be used as a heat storage medium and is available in a wide range of operating temperatures. Molten salt is one of the PCMs that has the advantage of a very high operating temperature. The PCM solidification simulation based on HitecXL molten salt using COMSOL Multiphysics software was carried out with variations in heat absorption of 1–5 kW/m2, assuming constant heat absorption. The results showed that the PCM solidification process started from the surface of the Stirling engine heat exchanger pipe. The part of the PCM that is solidified falls due to gravity, causing a phenomenon similar to a droplet. The flow that occurred was natural, driven by the buoyancy force resulting from density changes due to temperature gradients in the solidification process. The time required for the PCM to completely solidify was closely related to the amount of heat absorption; the greater the heat absorption from the pipe, the faster the PCM is fully solidified.

Evaluation of the pharmacokinetics of an experimental combined form of IFNα and IFNγ for intranasal use

Polypous rhinosinusitis is a chronic inflammatory disease of the nasal mucosa and paranasal sinuses. Recombinant interferon has antiproliferative activity and corrects the deficiency of endogenous regulatory molecules, which allows us to consider this class of immunotropic drugs as a promising component of conservative immunotherapy for polyposis rhinosinusitis. Purpose of the study: To select the optimal composition of the experimental composition of interferons and evaluate their pharmacokinetic parameters in laboratory animals.For laboratory evaluation of the effectiveness of the auxiliary components of the proposed composition in creating a local effect, Wistar rats in the amount of 30 animals were selected, to which the proposed form of the drug (IFN1) was administered once intranasally. The control group included 30 animals that were alternately administered intranasally with a similar dose of IFNα2b and IFNγ dissolved in water for injection (IFN2). Quantitative determination of interferon concentration in blood samples was carried out using the enzyme immunoassay method. To assess the dependence of changes in concentrations in the blood of animals on the time elapsed after their administration, standard pharmacokinetic models were used. Next, the integral from the initial moment of time to infinity was determined, which corresponded to the area under the pharmacokinetic curve and made it possible to calculate a number of pharmacokinetic characteristics.The following indicators were obtained: 1) Area under the pharmacokinetic curve (AUCt) ng/ml/min – IFN1 = 683.0; IFN2 = 1707.7. 2) Absorption constant (Kp) – IFN1 = 0.13096; IFN2 = 0.03836. 3) Suction constant (Kel) – IFN1 = 0.00177; IFN2 = 0.00317. 4) Clearance (Cl) ml/min – IFN1 = 129.35; IFN2 = 51.73.Based on the differences in the values of pharmacokinetic parameters (AUCt) for the IFN1 and IFN2 preparations, it can be concluded that the use of a composition based on chitosan, succinic acid and DMSO leads to a pronounced retention of interferon in the nasal mucosa, which provides a pronounced local therapeutic effect and allows for fewer systemic adverse reactions. This composition is suitable for further clinical studies of the effectiveness of immunotherapy for polyposis rhinosinusitis.

Enhanced Water Resistance of TiO2-GO-SMS-Modified Soil Composite for Use as a Repair Material in Earthen Sites.

Most earthen sites are located in open environments eroded by wind and rain, resulting in spalling and cracking caused by shrinkage due to constant water absorption and loss. Together, these issues seriously affect the stability of such sites. Gypsum-lime-modified soil offers relatively strong mechanical properties but poor water resistance. If such soil becomes damp or immersed in water, its strength is significantly reduced, making it unviable for use as a material in the preparation of earthen sites. In this study, we achieved the composite addition of a certain amount of sodium methyl silicate (SMS), titanium dioxide (TiO2), and graphene oxide (GO) into gypsum-lime-modified soil and analyzed the microstructural evolution of the composite-modified soil using characterization methods such as XRD, SEM, and EDS. A comparative study was conducted on changes in the mechanical properties of the composite-modified soil and original soil before and after immersion using water erosion, unconfined compression (UCS), and unconsolidated undrained (UU) triaxial compression tests. These analyses revealed the micro-mechanisms for improving the waterproof performance of the composite-modified soil. The results showed that the addition of SMS, TiO2, and GO did not change the crystal structure or composition of the original soil. In addition, TiO2 and GO were evenly distributed between the modified soil particles, playing a positive role in filling and stabilizing the structure of the modified soil. After being immersed in water for one hour, the original soil experienced structural instability leading to collapse. While the water absorption rate of the composite-modified soil was only 0.84%, its unconfined compressive strength was 4.88 MPa (the strength retention rate before and after immersion was as high as 93.1%), and the shear strength was 614 kPa (the strength retention rate before and after immersion was as high as 96.7%).

Pharmacometrics to Evaluate Dosing of the Patient-Friendly Ivermectin CHILD-IVITAB in Children ≥ 15 kg and

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h-1 (CV 19%) for CHILD-IVITAB vs. 1.56 h-1 (CV 43%) for STROMECTOL®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults.

Predicting Human Subcutaneous Bioavailability of Therapeutic Monoclonal Antibodies from Systemic Clearance and Volume of Distribution.

Subcutaneous delivery of monoclonal antibody therapeutics is often preferred to intravenous delivery due to better patient compliance and overall lower cost to the healthcare system. However, the systemic absorption of biologics dosed subcutaneously is often incomplete. The aim of this work was to describe a human bioavailability prediction method for monoclonal antibodies delivered subcutaneously that utilizes intravenous pharmacokinetic parameters as input. A two-compartment pharmacokinetic model featuring a parallel-competitive absorption pathway and a presystemic metabolism pathway was employed. A training data set comprised 19 monoclonal antibodies (geometric mean bioavailability of 68%), with previously reported human pharmacokinetic parameters, while a validation set included data compiled from 5 commercial drug products (geometric mean bioavailability of 69%). A single fitted absorption rate constant, paired with compound-specific estimates of presystemic metabolism rate proportional to compound-specific systemic clearance parameters, resulted in calculations of human subcutaneous bioavailability closely mimicking clinical data in the training data set with a root-mean-square error of 5.5%. Application of the same approach to the validation data set resulted in predictions characterized by 12.6% root-mean-square error. Factors that may have impacted the prediction accuracy include a limited number of validation data set compounds and an uncertainty in the absorption rate, which were subsequently discussed. The predictive method described herein provides an initial estimate of the subcutaneous bioavailability based exclusively on pharmacokinetic parameters available from intravenous dosing.

Population pharmacokinetic study and application of ticagrelor and AR-C124910XX after percutaneous coronary intervention in Chinese patients with acute coronary syndrome.

This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization. Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology. The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased. The study offers key insights into ticagrelor's dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.

First-Principles Calculations on Electronic, Optical, and Phonon Properties of γ-Bi2MoO6.

The wide band gap γ-Bi2MoO6 (BMO) has tremendous potential in emergent solar harvesting applications. Here we present a combined experimental-first-principles density functional theory (DFT) approach to probe physical properties relevant to the light sensitivity of BMO like dynamic and structural stability, Raman and infrared absorption modes, value and nature of band gap (i.e., direct or indirect), dielectric constant, and optical absorption, etc. We solvothermally synthesized wide band gap Pca21 phase pure BMO (≳3 eV) for two different pH values of 7 and 9. The structural parameters were correlated with the stability of BMO derived from elastic tensor simulations. The desired dynamical stability at T = 0 K was established from the phonon vibrational band structure using a finite difference-based supercell approach. The DFT-based Raman modes and phonon density of states (DOS) reliably reproduced the experimental Raman and infrared absorption. The electronic DOS calculated from Heyd-Scuseria-Ernzerhof HSE06 with van der Waals (vdW) and relativistic spin-orbit coupling (SOC) corrections produced a good agreement with the band gap obtained from diffuse reflectance spectroscopy (DRS). The optical absorption obtained from the complex dielectric constant for the HSE06+SOC+vdW potential closely resembled the DRS-derived absorption of BMO. The BMO shows ∼43% photocatalytic efficiency in degrading methylene blue dye under 75 min optical illumination. This combined DFT-experimental approach may provide a better understanding of the properties of BMO relevant to solar harvesting applications.

First principle investigation of structural, optoelectronic and thermoelectric properties of lead-free Cs2AgAuX6 (X= Br, I) for energy harvesting applications

In this research work, the properties of double perovskites (DPs) are investigated by using the full potential linear augmented plane-wave (FP-LAPW) technique. To compute structural characteristics, we used the generalized gradient approximation (GGA) functional. On the other hand, the optoelectronic and thermoelectric properties of Cs2AgAuX6 (X = Br, I), were calculated using the modified Becke and Johnson (mBJ) potential functional. According to our work, these materials have band gaps of 1.13 eV for X = I and 1.24 eV for X = Br. These materials' optical properties have been investigated through the use of reflectivity, absorption, refractive index, and dielectric constants. With the highest transition values versus photon energy in the visible spectrum, the optical properties point to the potential application of these double perovskites in solar cells. In addition, our studies of the transport properties using the Boltzmann transport equation suggest that our understudy DPs is optimal for thermoelectric uses.

In vitro evaluation and in situ intestinal absorption characterisation of paeoniflorin nanoparticles in a rat model.

Purpose: the aim of this study was to improve the stability and bioavailability of paeoniflorin (PF) by using nanoparticle encapsulation technology. Methods: paeoniflorin nanoparticles (PF NPs) were prepared with PLGA as the carrier using the compound emulsion method. The nanoparticles were characterised by using a Malvern laser particle sizer, transmission electron microscope (TEM), X-ray diffraction (XRD) analyser, and Fourier-transform infrared (FT-IR) spectrometry. The PF NPs were subjected to a series of stability investigations (such as for 4 °C storage stability, pH stability, and thermal stability), lyophilisation protection technology investigations, and in vitro release studies. Finally, the intestinal absorption properties of PF and PF NPs were studied by the in situ single-pass intestinal perfusion (SPIP) rat model, using the effective permeability coefficient (P eff) and the absorption rate constant (K a) as relevant indexes. Results: the prepared nanoparticles had a particle size of 105.0 nm with blue opalescent, rounded morphology, uniform size, good stability and slow release. We found that 4% alginate was the best lyoprotectant for the PF NPs. In the intestinal absorption experiments, P eff was higher for the PF NPs group compared with the original PF material drug group in all intestinal segments (P < 0.05), and the absorption rate constant K a increased with the increase in the drug concentration. Conclusion: the nanoparticles produced by this method have good stability and a slow-release effect; they can thus improve the absorption of PF in rat intestines, helping improve the stability and bioavailability of PF and enhancing its pharmacological effects.

Doxycycline pharmacokinetics and tissue depletion in striped catfish (Pagasianodon hypophthalmus) after oral administration.

The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (ka), absorption half-life (T1/2abs), maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), and area under the plasma concentration-time curve from time 0 to 96 h (AUC0-96 h) which were 0.12 h-1, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.

Heat absorption effect of magneto-natural convection flow in vertical concentric annuli with influence of radial and induced magnetic field

This paper aims to study the natural convective magneto-hydrodynamic flow of fluid through vertical concentric annuli with iso-flux heating under the conditions of constant internal heat absorption and an induced magnetic field. By solving the set of dimensionless coupled governing equations, we were able to obtain exact expressions for the temperature field, velocity field, and induced magnetic field. We also managed to derive the formulas for skin friction, mass flux, and induced current density. We also examined the effects of non-dimensional parameters on skin friction and mass flux. For easy comprehension and interpretation, the results are provided graphically and in tabular form. The heat absorption parameter, the induced current density, the induced magnetic field, and velocity exhibit a negative trend as the Hartmann number (Ha) value increases. The induced magnetic field has the effect of raising both the induced current density and velocity profile. It is found that, when a fluid absorbs heat, the heat absorption parameter experiences reverse flow. For the heat-absorbing fluids, the radii ratio has the effect of increasing velocity, induced magnetic field, and induced current density. The numerical values of skin friction and mass flux at cylindrical walls increase (decrease) with increasing heat absorption parameter and generally it has decreasing tendency with increasing Hartmann number

Simulation on solidification process of molten salt-based phase change material as thermal energy storage medium for application in Stirling engine

Abstract Thermal energy storage technologies have been widely used to mitigate intermittency from renewable energy such as solar energy. Phase change material (PCM) is a certain material that can be used as a heat storage medium and is available in a wide range of operating temperatures. Molten salt is one of the PCMs that has the advantage of a very high operating temperature. The PCM solidification simulation based on HitecXL molten salt using COMSOL Multiphysics software will be carried out with variations in heat absorption of 1 - 5 kW/m2, assuming constant heat absorption. The results show that the PCM solidification process starts from the surface of the Stirling engine heat exchanger pipe. The part of the PCM that has been solidified will fall following the direction of gravity and cause a phenomenon such as a droplet. The flow that occurs is a natural flow caused by the buoyancy force due to changes in density due to temperature gradients in the solidification process. The time required for the PCM to completely solidify is closely related to the amount of heat absorption. The greater the heat absorption from the pipe, the faster the PCM to fully solidified.

Frequency selective surface with quad-band absorption/transmission and angular stability for TE and TM polarizations

The proposed FSS structure employs two square annular rings for absorption functionalities and two square aperture slots for transmission properties. Through comprehensive simulations and analysis, the FSS structure demonstrates remarkable performance in selectively absorbing and transmitting electromagnetic waves across four distinct frequency bands. Moreover, the design exhibits excellent TE and TM polarizations angular stability, consistently maintaining constant absorption and transmission characteristics across varying incidence angles. A comprehensive analysis of the equivalent circuit model of the FSS structure has also been performed to understand the quad-band transmission and absorption properties. The measurement results underscore the effectiveness of the design of a 250*250 mm array, with absorption peaks notably occurring at 4.2 GHz and 7.23 GHz, boasting peak absorption rates of 92% and 85%, respectively. Moreover, the insertion loss within the pass band at 8.8 GHz and 12.2 GHz stands impressively low at 0.2 dB and 0.32 dB, respectively. Notably, the proposed quad-band FSS showcases polarization-insensitive behavior across a range from 0° to 60° and successfully undergoes conformal testing with a curvature radius up to 50 mm. The results of experimental testing on a quad-band FSS prototype demonstrate superior agreement with those obtained through simulations and analytically derived equivalent circuit model (ECM) results, validating its practical applicability in real-world scenarios.