Development of a RP-HPLC method for evaluation of in vitro permeability of voriconazole in the presence of enhancers through rat skin

AbstractAn isocratic RP-HPLC–UV method for the analysis of voriconazole in skin diffusate samples has been developed and validated. Experimental design was employed to optimize the method. The method was validated as per ICH guidelines. Linearity was observed over the concentration range of 2–100μgmL−1 (r2=0.999). Limits of detection and quantification were 0.6 and 2μgmL−1, respectively. Intra-day and inter-day precision (% RSD) was within the ICH limits (⩽2%). The method was successfully used to analyze skin diffusate samples, and the effectiveness of different permeation enhancers was compared with respect to flux and permeability coefficient

Corrosion behaviour of porous Ti intended for biomedical applications

Porous Ti implants are being developed inorder to reduce the biomechanical mismatch between theimplant and the bone, as well as increasing the osseointegrationby improving the bone in-growth. Most of the focusin the literature has been on the structural, biological andmechanical characterization of porous Ti whereas there islimited information on the electrochemical characterization.Therefore, the present work aims to study the corrosionbehaviour of porous Ti having 30 and 50 % ofnominal porosity, produced by powder metallurgy routeusing the space holder technique. The percentage, size anddistribution of the pores were determined by image analysis.Electrochemical tests consisting of potentiodynamicpolarization and electrochemical impedance spectroscopywere performed in 9 g/L NaCl solution at body temperature.Electrochemical studies revealed that samples presenteda less stable oxide film at increased porosity, morespecifically, the complex geometry and the interconnectivityof the pores resulted in formation of less protectiveoxide film in the pores.This study was supported by FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalizac¸a˜o (POCI) with the reference project POCI-01-0145- FEDER-006941, Programa de Acc¸o˜es Universita´rias Integradas LusoFrancesas’ (PAUILF TC-12_14), and The Calouste Gulbenkian Foundation through ‘‘Programa de Mobilidade Acade´mica para Professores’’. The authors would also like to acknowledge Prof. Ana Senos (University of Aveiro) and Prof. Jose´ Carlos Teixeira (University of Minho) for the provision of the characterization facilities.info:eu-repo/semantics/publishedVersio

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Die Level 3D Heterogeneous Integration of a Microfluidic System

Lab-on-a-chip (LOC) devices has enabled handheld sensing systems for chemical analysis and biological detection. Stacking based integration of various components of an LOC device would lead to system miniaturization and would allow accommodation of more functionalities in a given volume. In this paper, we report a 3D integrated heterogenous system incorporating a silicon photodetector, optical plastic filters, glass microfluidic device and an LED all stacked in 3D and interconnected to function as a fluorescence detection platform. Processing methodology and testing results are reported here

Deformation and fracture behavior of laser processed dense and porous Ti6Al4V alloy under static and dynamic loading

Deformation and fracture behavior of laser processed dense and porous Ti6Al4V alloy under uniaxial static and dynamic compression loadings were experimentally investigated in this study. Samples with 0, 10 and 20 porosities were fabricated using a continuous wave Nd-YAG laser in a controlled environment. The dynamic tests were performed at the strain rates of 1�10 3, 4�10 3 and 8�10 3/s using the split Hopkinson pressure bar (SHPB) test system and the static tests were done at the strain rate of 1�10 -3/s. In addition, SEM and EBSD analyses were also carried out to study the failure mechanisms and texture development due to solidification and deformation. Both deformation and fracture exhibited appreciable rate sensitivity. For the former, the material strength increased, and for the latter, the failure strains decreased with the increased strain rates. The 20 porous Ti6Al4V showed lower strength, but higher ductility compared to the 10 material, but the 10 porous material had both less strength and ductility than the dense (0 porosity) material and the ductility of 20 porous material was only comparable to that of the dense material, i.e., did not exhibit appreciable increase of ductility. The texture analysis indicated that all the samples had reasonably consistent textures due to solidification. Hence the texture effect is essentially negligible and the observed material behavior is mainly a manifestation of the induced porosity. Both the macroscopic experiments and the microstructure analysis suggest that the formation of adiabatic shear band (ASB) could likely be the major failure mechanism for Ti6Al4V and the pores likely be the sites for nucleating ASB and subsequent catastrophic failure. For initially dense Ti6Al4V, the failure and the corresponding failure strain seem to depend on the duration of the incubation period for developing a nucleation site. © 2012 Elsevier B.V

Quality by Design (QbD) approach to develop HPLC method for eberconazole nitrate: Application oxidative and photolytic degradation kinetics

Stability of eberconazole nitrate (EBZ) was investigated using a stability indicating HPLC method. Quality by Design (QbD) approach was used to facilitate method development. EBZ was exposed to different stress conditions, including hydrolytic (acid, base, neutral), oxidative, thermal and photolytic. Relevant degradation was found to take place in all the conditions. The degradation of EBZ followed (pseudo) first-order kinetics under experimental conditions. The kinetic parameters (rate constant, t1/2, and t90) of the degradation of EBZ were calculated

Gallium Nitride transistor on glass using epoxy mediated substrate transfer technology

Low cost high-power electronics era has begun with the fabrication of Gallium Nitride (GaN) based High Electron Mobility Transistors (HEMTs) on Silicon substrates. Silicon is however not an optimum material from the viewpoint of the final substrate. Having GaN based devices on other substrates would enable better performing RF and high-power devices. Here we report the process development of the transfer technology, of a fabricated GaN HEMT transistors to a glass wafer using temporary bonding material. Epoxy has been used to finally bond the GaN stack and the glass wafer. Transfer and output characteristics of the HEMT and the capacitance measurements of the capacitors were performed on the identical devices before and after the transfer process. Also, to understand the stress before and after the transfer process Raman measurements were carried out

Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice

Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids