Study of Texture Analysis on Asymmetric Cryorolled and Annealed CoCrNi Medium Entropy Alloy

CoCrNi equiatomic medium entropy alloy sheets were prepared by asymmetric rolling, cryorolling, and asymmetric cryorolling. The asymmetric cryorolled samples exhibited a noteworthy ultra-fine-grain heterogeneous lamella structure. The microstructure and corresponding hardness obtained by different rolling processes and subsequent annealing are compared. It can be seen from the results that the cryogenic deformation temperature had a stronger effect on the mechanical properties of the medium entropy alloys (MEA), compared with the shear strain caused by the asymmetric cryorolling. The effect of annealing temperature on texture components and volume fractions of the specially rolled samples was also analyzed. The result revealed that the recrystallized MEA exhibited similar texture components and the corresponding volume fraction, which indicated that the rolling process had limited influence on the formation of annealing texture. The recrystallized texture after annealing retained the deformation texture and twin related orientations appeared. Asymmetric rolled MEA showed strong random composition than symmetric rolled MEA regardless of rolling temperature. The recrystallized textures of the species obtained by the three rolling processes did not exhibit a significant dependence on the annealing temperature

Recent Development of Superplasticity in Aluminum Alloys: A Review

Aluminum alloys can be used in the fabrication of intricate geometry and curved parts for a wide range of uses in aerospace and automotive sectors, where high stiffness and low weight are necessitated. This paper outlines a review of various research investigations on the superplastic behavior of aluminum alloys that have taken place mainly over the past two decades. The influencing factors on aluminum alloys superplasticity, such as initial grain size, deformation temperature, strain rate, microstructure refinement techniques, and addition of trace elements in aluminum alloys, are analyzed here. Since grain boundary sliding is one of the dominant features of aluminum alloys superplasticity, its deformation mechanism and the corresponding value of activation energy are included as a part of discussion. Dislocation motion, diffusion in grains, and near-grain boundary regions being major features of superplasticity, are discussed as important issues. Moreover, the paper also discusses the corresponding values of grain size exponent, stress exponent, solute drag creep and power law creep. Constitutive equations, which are essential for commercial applications and play a vital role in predicting and analyzing the superplastic behavior, are also reviewed here

The Cold Angular Rolling Process of Copper Sheets: Unraveling Plastic Deformation Behavior and Unveiling Microstructural Transformations

The cold angular rolling process (CARP) is being developed as a continuous severe plastic deformation technique, which can process metal sheets without any length limitations at room temperature. CARP contains cold rolling and equal-channel angular process components. The sheet thickness is kept consistent before and after CARP, allowing multiple passes of the sheet. The desired microstructure and mechanical properties can be achieved in the processed metallic sheets. The current study is aimed to evaluate the capability of CARP by processing copper sheets with different sheet widths for repetitive passes. The CARP-treated sheets are examined by lab-scale X-ray and high-energy synchrotron X-ray diffraction to investigate the evolution in dislocation density, texture, and strain anisotropy, and by tensile testing to identify the bulk mechanical properties. The digital image correlation method is applied to tensile testing so that strain localization within the sample gauge is visualized and deformation behavior is evaluated after yielding till postnecking by estimating the hardening exponent and strain hardening rate of the CARP-treated sheet. Comparing the reported continuous and multiple-step processes on Cu and its alloys, the present study confirms that the CARP is potentially a useful sheet process for strengthening ductile metals

Determinants of Herpetofaunal Diversity in a Threatened Wetland Ecosystem: A Case Study of the Ramaroshan Wetland Complex, Western Nepal

Wetlands are among the highly threatened ecosystems due to anthropogenic activities. The Ramaroshan Wetland Complex (RWC) of Achham District, Nepal is one of the high-altitude wetlands facing human induced degradation and loss. Herpetofauna are key bio-indicators of environmental health and habitat quality and are useful to assess habitat conditions of such threatened ecosystems. This study quantified the land use and land cover (LULC) change in the RWC and documented the diversity and distribution pattern of herpetofauna. The LULC in the area (13.94 Km2) was analyzed for 1989, 2000, 2010 and 2021 by supervised classification of remote sensing images. Surveys were conducted along 25 transects, each of 200 m in length and environmental variables were recorded for every observation of herpetofauna. The LULC analysis revealed an overall loss of 16% of the total water body between 1989 (0.25 Km2) and 2021 (0.21 Km2). Eleven species of herpetofauna (five amphibians and six reptiles) within five families and two orders (i.e., Anura and Squamata), were recorded with low diversity (H’ = 1.88312) and evenness (E = 0.3642) indices. The herpetofauna had a hump-shaped distribution along the elevation gradient with the highest richness and abundance at 2300 m asl. Amphibian abundance decreased with increasing distance to nearest water sources, whereas reptile abundance increased. Amphibians were more abundant in agricultural field and marsh land, whereas reptile abundance was higher around human settlements. Results indicate that the wetland area in the RWC is declining at an alarming rate and, in turn, might account for the low diversity and abundance of the herpetofauna

In Depth Analysis of Pressure-Sensitive Adhesive Patch-Assisted Delivery of Memantine and Donepezil Using Physiologically Based Pharmacokinetic Modeling and in Vitro/in Vivo Correlations

The objective of this work was to evaluate the feasibility of transdermal delivery of two widely prescribed dementia drugs for the Alzheimer’s disease. In this regard, the drug in adhesive patches of memantine (ME) co-loaded with donepezil (DO) was prepared using an ethylene vinyl acetate polymer and characterized for drug content, the crystallinity of drugs in the polymer matrix, and in vitro permeation. To understand the different physical and chemical processes underlying the percutaneous absorption, it is required to employ a comprehensive model that accounts for the anatomy and physiology of the skin. A transdermal physiologically based pharmacokinetic (TPBPK) model was developed and was integrated in a compartmental pharmacokinetic model to predict the plasma drug concentrations in rats. The model predictions showed a good fit with the experimental data, as evaluated by the prediction error calculated for both drugs. It was evident from the simulations that the drug diffusivity and partition coefficient in the polymer matrix are the critical parameters that affect the drug release from the vehicle and subsequently influence the in vivo pharmacokinetic profile. Moreover, a correlation function was built between the in vitro permeation data and in vivo absorption for both ME and DO. A good point-to-point in vitro/in vivo correlation (IVIVC, Level A correlation) was achieved by predicting the plasma concentrations with convolution for the entire study duration. The results of our study suggested that the implementation of mechanistic modeling along with IVIVC can be a valuable tool to evaluate the relative effects of formulation variables on the bioavailability from transdermal delivery systems

Evaluation of interconversion pharmacokinetics of 16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide – a novel HMG-CoA reductase inhibitor and its acid metabolite using multi-compartmental pharmacokinetic model in mice

<p></p><p>16α-Hydroxycleroda-3,13(14)Z-dien-15,16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti-hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties.</p><p>The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6 and 12 mg/kg separately. The oral PK study of 4655K-09 was carried out at therapeutic dose of 25 mg/kg.</p><p>The % AUC of metabolite converted to parent upon its administration <math><mrow><msubsup><mrow><mi>%</mi><mi> </mi><mi>A</mi><mi>U</mi><mi>C</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow></msubsup></mrow></math> was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. Further, the role of interconversion in pharmacokinetics of 4655K-09 was evaluated through secondary parameters like conversion coefficients of parent to metabolite (<math><msubsup><mrow><mi>K</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow></msubsup><mo>:</mo><mn>0.08</mn><mo> </mo><mo>±</mo><mo> </mo><mn>0.02</mn></math>), metabolite to parent (<math><msubsup><mrow><mi>K</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow></msubsup></math>: 0.019 ± 0.001), exposure enhancement (EE: 1.04 ± 0.006), and recycled fraction (RF: 0.042 ± 0.007), highlighted the minimal role of interconversion. The estimation of oral bioavailability remains unaffected when calculated through considering reversible metabolism.</p><p>The present model-based interconversion pharmacokinetics of 4655K-09 in mice could be further extended to other species to support its development as anti-hyperlipidemic agent.</p><p></p> <p>16α-Hydroxycleroda-3,13(14)Z-dien-15,16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti-hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties.</p> <p>The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6 and 12 mg/kg separately. The oral PK study of 4655K-09 was carried out at therapeutic dose of 25 mg/kg.</p> <p>The % AUC of metabolite converted to parent upon its administration <math><mrow><msubsup><mrow><mi>%</mi><mi> </mi><mi>A</mi><mi>U</mi><mi>C</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow></msubsup></mrow></math> was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. Further, the role of interconversion in pharmacokinetics of 4655K-09 was evaluated through secondary parameters like conversion coefficients of parent to metabolite (<math><msubsup><mrow><mi>K</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow></msubsup><mo>:</mo><mn>0.08</mn><mo> </mo><mo>±</mo><mo> </mo><mn>0.02</mn></math>), metabolite to parent (<math><msubsup><mrow><mi>K</mi></mrow><mrow><mi>K</mi><mo>-</mo><mn>09</mn></mrow><mrow><mi>K</mi><mo>-</mo><mn>9</mn><mi>T</mi></mrow></msubsup></math>: 0.019 ± 0.001), exposure enhancement (EE: 1.04 ± 0.006), and recycled fraction (RF: 0.042 ± 0.007), highlighted the minimal role of interconversion. The estimation of oral bioavailability remains unaffected when calculated through considering reversible metabolism.</p> <p>The present model-based interconversion pharmacokinetics of 4655K-09 in mice could be further extended to other species to support its development as anti-hyperlipidemic agent.</p