Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

Directory of Open Access Journals (Sweden)

Rita R Alloway

2017-11-01

Full Text Available Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand" product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant.From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35 or liver transplant (n = 36. Abbreviated New Drug Applications (ANDA data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

Science.gov (United States)

Padgaonkar, K A; Revankar, S N; Bhatt, A D; Vaz, J A; Desai, N D; D'Sa, S; Shah, V; Gandewar, K

1999-07-01

To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology

DEFF Research Database (Denmark)

Garcia Ortiz, Patricia Elodia; Hansen, S H; Shah, Surendra P.

2011-01-01

To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.......To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

Science.gov (United States)

Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

2017-12-05

The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

Science.gov (United States)

Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

2017-02-01

The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

Science.gov (United States)

Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

2011-06-01

The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.

Science.gov (United States)

Slingerland, Marije; Guchelaar, Henk-Jan; Rosing, Hilde; Scheulen, Max E; van Warmerdam, Laurence J C; Beijnen, Jos H; Gelderblom, Hans

2013-12-01

Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties. Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration. Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa. Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia. At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Bioequivalence of a new cyclosporine a formulation to Neoral.

Science.gov (United States)

David-Neto, Elias; Kakehashi, Erica; Alves, Cristiane Feres; Pereira, Lilian M; de Castro, Maria Cristina R; de Mattos, Renata Maciel; Sumita, Nairo Massakazu; Romano, Paschoalina; Mendes, Maria Elizabete; Nahas, William Carlos; Ianhez, Luiz Estevam

2004-02-01

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

Regulatory and clinical aspects of psychotropic medicinal products bioequivalence.

Science.gov (United States)

Bałkowiec-Iskra, Ewa; Cessak, Grzegorz; Kuzawińska, Olga; Sejbuk-Rozbicka, Katarzyna; Rokita, Konrad; Mirowska-Guzel, Dagmara

2015-07-01

Introduction of generic medicinal products to the market has increased access to modern therapies but also enabled significant reduction in their cost, leading to containment of public expenditures on medicinal products reimbursement. The critical assessment of bioequivalence of any reference medicinal product and its counterpart is based on comparison of their rate and extent of absorption. It is assumed that two medicinal products are bioequivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. Bioequivalent medicinal products are declared to be also therapeutically equivalent and can be used interchangeably. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of this article is to provide a description of rules that guide registration of generic medicinal products in the European Union and to analyze specific examples from the scientific literature concerning therapeutic equivalence of reference and generic antidepressant and antipsychotic medicinal products. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

Science.gov (United States)

Shahiwala, Aliasgar; Zarar, Aisha

2018-01-01

In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparative bioequivalence assessment of aspirin tablets marketed ...

African Journals Online (AJOL)

Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

Evaluation of two novel tablet formulations of artemether-lumefantrine (Coartem) for bioequivalence in a randomized, open-label, two-period study.

Science.gov (United States)

Lefèvre, Gilbert; Bhad, Prafulla; Jain, Jay Prakash; Kalluri, Sampath; Cheng, Yi; Dave, Hardik; Stein, Daniel S

2013-09-08

Artemether-lumefantrine (Coartem; AL) is a standard of care for malaria treatment as an oral six-dose regimen, given twice daily over three days with one to four tablets (20/120 mg) per dose, depending on patient body weight. In order to reduce the pill burden at each dose and potentially enhance compliance, two novel fixed-dose tablet formulations (80/480 mg and 60/360 mg) have been developed and tested in this study for bioequivalence with their respective number of standard tablets. A randomized, open-label, two-period, single-dose, within formulation crossover bioequivalence study comparing artemether and lumefantrine exposure between the novel 80/480 mg tablet and four standard tablets, and the novel 60/360 mg tablet and three standard tablets, was conducted in 120 healthy subjects under fed conditions. Artemether, dihydroartemisinin, and lumefantrine were measured in plasma by HPLC/UPLC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analyses. Adjusted geometric mean AUClast for artemether were 345 and 364 ng·h/mL (geometric mean ratio (GMR) 0.95; 90% CI 0.89-1.01) and for lumefantrine were 219 and 218 μg·h/mL (GMR 1.00; 90% CI 0.93-1.08) for 80/480 mg tablet versus four standard tablets, respectively. Corresponding Cmax for artemether were 96.8 and 99.7 ng/mL (GMR 0.97; 90% CI 0.89-1.06) and for lumefantrine were 8.42 and 8.71 μg/mL (GMR 0.97; 90% CI 0.89-1.05). For the 60/360 mg tablet versus three standard tablets, adjusted geometric mean AUClast for artemether were 235 and 231 ng·h/mL (GMR 1.02; 90% CI 0.94-1.10), and for lumefantrine were 160 and 180 μg·h/mL (GMR 0.89; 90% CI 0.83-0.96), respectively. Corresponding Cmax for artemether were 75.5 and 71.5 ng/mL (GMR 1.06; 90% CI 0.95-1.18), and for lumefantrine were 6.64 and 7.61 μg/mL (GMR 0.87; 90% CI 0.81-0.94), respectively. GMR for Cmax and AUClast for artemether and lumefantrine for all primary comparisons were within the bioequivalence acceptance criteria (0

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

Science.gov (United States)

Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

2013-11-01

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

Directory of Open Access Journals (Sweden)

Zhou X

2015-02-01

Full Text Available Xiao Zhou, Ji Liu Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4% for the area under the plasma concentration–time curve (AUC from time zero to the last measurable concentration, 99.6% (94.2%–102.7% for the AUC from administration to infinite time, and 100.8% (93.1%–106.4% for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules were bioequivalent. Keywords: tramadol hydrochloride, in vitro release, pharmacokinetic, bioequivalence, fluorescence detector

Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

Science.gov (United States)

García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

2016-05-01

The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

Science.gov (United States)

Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

Science.gov (United States)

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

2013-12-01

Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE... test product and the reference material should be administered to subjects in the fasting state, unless...

Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.

Science.gov (United States)

Kurczewski, Renee; Bowen, Chet; Collins, David; Zhu, John; Serbest, Gulyeter; Manyak, Michael

2017-09-01

A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart ® ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (C max ) and area under the serum concentration-time curve (AUC 0-t ) for dutasteride and tamsulosin, and AUC 0-∞ for tamsulosin. The 90% confidence intervals for the ratios of the C max and AUC 0-t (for dutasteride and tamsulosin) and for AUC 0-∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states. © 2017, The American College of Clinical Pharmacology.

Consumer's risk in the EMA and FDA regulatory approaches for bioequivalence in highly variable drugs.

Science.gov (United States)

Muñoz, Joel; Alcaide, Daniel; Ocaña, Jordi

2016-05-30

The 2010 US Food and Drug Administration and European Medicines Agency regulatory approaches to establish bioequivalence in highly variable drugs are both based on linearly scaling the bioequivalence limits, both take a 'scaled average bioequivalence' approach. The present paper corroborates previous work suggesting that none of them adequately controls type I error or consumer's risk, so they result in invalid test procedures in the neighbourhood of a within-subject coefficient of variation osf 30% for the reference (R) formulation. The problem is particularly serious in the US Food and Drug Administration regulation, but it is also appreciable in the European Medicines Agency one. For the partially replicated TRR/RTR/RRT and the replicated TRTR/RTRT crossover designs, we quantify these type I error problems by means of a simulation study, discuss their possible causes and propose straightforward improvements on both regulatory procedures that improve their type I error control while maintaining an adequate power. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A pharmacokinetic and bioequivalence study of Contiflo ICON 400 µg tablets in healthy Indian subjects.

Science.gov (United States)

Monif, T; Arora, V; Madan, S; Arora, R; Balaji, A; Jha, D; Thudi, N R

2010-12-01

Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in human prostate. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of benign prostatic hypertrophy. A new formulation Contiflo ICON 400 µg has been developed by Ranbaxy Laboratories Limited, India similar to Flomaxtra XL 400 µg of Astellas Pharma Limited, United Kingdom. This product is specifically designed to achieve a more consistent plasma concentration over a period of 24-h, a lower maximum plasma concentration (Cmax) and an independence of pharmacokinetics (PKs) on food intake. The objective of the present study was to evaluate the pharmacokinetics and bioequivalence of the new formulation Contiflo ICON 400 µg of Ranbaxy Laboratories Limited, India and Flomaxtra XL 400 µg prolonged release tablets (containing tamsulosin hydrochloride prolonged release 400 µg) of Astellas Pharma Limited, United Kingdom. Study was conducted as an open label, balanced, randomized, two-treatment, two-period, two-sequence, cross over, single-dose bioequivalence study in 32 adult male human subjects under fed conditions. The mean (range) age, weight and height of the study subjects were 27.03 years (19 - 40 years), 57.19 kg (48 - 72 kg) and 166.81 cm (154 - 181 cm) respectively. Blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 20, 24, 36, 48, 72, and 96 h post dose in each period. Plasma samples were analyzed for tamsulosin by using validated liquid chromatographic mass spectrometry (LC-MS/MS) method. The Mean ± SD of pharmacokinetic parameters tmax, Cmax, AUC24, AUClast and AUCinf for Tamsulosin were 11.741 ± 4.7201 and 12.155 ± 6.3077 h, 10.7614 ± 4.76709 and 10.4954 ± 5.08979 ng/ml, 171.4674 ± 77.39695 and 160.6738 ± 77.98628 ng.h/ml, 262.7771 ± 150.21432 and 250.6854 ± 156.75581 ng

Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

Science.gov (United States)

Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

2012-04-01

FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

Bioequivalence of three florfenicol preparations in broilers

Directory of Open Access Journals (Sweden)

Husamettin Ekici

2014-12-01

Full Text Available This study was aimed to determine the bioequivalence of three different preparations of florfenicol using non-drugged broiler chickens. A total of 28 broiler chickens aging 30-day were divided into four equal groups; these were Group I, II, III, and IV. The birds of Group I (for effective substance were given intravenous (i.v. administration of florfenicol dosed at 40 mg/kg body weight (b.wt.. The birds of Group II (for reference drug, Group III (for test-1 drug, and Group IV (for test-2 drug received florfenicol preparations with water (dosed at 40 mg/kg b.wt. through intracrop administration. Blood samples were collected periodically from the birds of all four groups, and blood plasma was separated. Levels of florfenicol and its metabolite (florfenicol amine in the plasma were measured by High Performance Liquid Chromatography (HPLC. In this study, the limit of detection (LOD for florfenicol and florfenicol amine were recorded as 0.017 and 0.78 µg/mL, respectively. On the other hand, the recovery of florfenicol and florfenicol amine were 83.4-84.6 and 82.2-83.8%, respectively. Based on the values of area under the curve (AUC, maximum concentration (Cmax, and time to maximum concentration (Tmax, test-1 drug was found to be acceptable, whereas test-2 drug was remained below the acceptable limits (80-125% of AUC and Cmax. Thus, it was concluded that test-1 drug was bioequivalent as compared to the reference drug.

The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

Science.gov (United States)

Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

2016-03-01

Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

Science.gov (United States)

2012-02-22

... recommendations provide product-specific guidance on the design of BE studies to support abbreviated new drug... the process that would be used to make product-specific BE recommendations available to the public on... ``Bioequivalence Recommendations for Specific Products,'' which explained the process that would be used to make...

Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

Science.gov (United States)

Ibarra, Manuel; Valiante, Cristian; Sopeña, Patricia; Schiavo, Alejandra; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

2018-06-15

Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®. In silico simulations for Dilatrend® were compared with published results of bioequivalence studies performed in fasting conditions allowing model development through a learning and confirming process. Single-dose pharmacokinetic profiles were then simulated for the brand-name drug and two similar drug products selected according to in vitro observations, in a virtual Caucasian population of 1000 subjects (50% male, aged between 18 and 50 years with standard body-weights). Population bioequivalence ratios were estimated revealing that in vitro differences in drug release would have a major impact in carvedilol maximum plasma concentration, leading to a non-bioequivalence outcome. Predictions support the need to perform in vivo bioequivalence for these products of extensive use. Application of the in vitro-in silico-in vivo approach stands as an interesting alternative to tackle and reduce drug product variability in biopharmaceutical quality. Copyright © 2018 Elsevier B.V. All rights reserved.

78 FR 66743 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability

Science.gov (United States)

2013-11-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability AGENCY... guidance, FDA recommended an in vivo fasting BE study with pharmacokinetic endpoints and in vitro studies...

75 FR 33311 - Guidance for Industry on Bioequivalence Recommendations for Specific Products; Availability

Science.gov (United States)

2010-06-11

... available recommendations on how to design product-specific BE studies to support ANDAs. Under this process... thinking on a new process for making available to sponsors FDA guidance on how to design product-specific... ``Bioequivalence Recommendations for Specific Products.'' This guidance describes a new process for making...

Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

Directory of Open Access Journals (Sweden)

2000-03-01

Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

Directory of Open Access Journals (Sweden)

Werawath Mahatthanatrakul

2008-05-01

Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

Directory of Open Access Journals (Sweden)

Zhang Y

2017-07-01

Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

Science.gov (United States)

Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

2009-01-01

The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

Pharmacokinetic comparison and bioequivalence evaluation of losartan/ hydrochlorothiazide tablet between Asian Indian and Japanese volunteers.

Science.gov (United States)

Kumar, Sudershan; Monif, Tausif; Khuroo, Arshad; Reyar, Simrit; Jain, Rakesh; Singla, Ajay K; Kurachi, Kazuya

2014-01-01

To demonstrate the bioequivalence between the test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablet and evaluate the effect of ethnicity on pharmacokinetics properties of losartan, losartan carboxylic acid and hydrochlorothiazide on healthy Asian Indian and Japanese volunteers. Randomized, open-label, crossover, bioavailability studies were conducted separately in healthy Asian Indian and Japanese volunteers. One tablet either of test or of reference product was administered after 10 hours of overnight fasting. After dosing, serial blood samples were collected for a period of 48 hours for both the studies. Plasma samples were analyzed for losartan, losartan carboxylic acid and hydrochlorothiazide by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0-t, AUC0-∞, Cmax, tmax, and other pharmacokinetics parameters were determined from plasma concentration-time profiles for both test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablets. Statistical evaluations were done to evaluate bioequivalence between generic test formulation (EPR0001) and Japanese reference product (Preminent®). Losartan, losartan carboxylic acid and hydrochlorothiazide were well tolerated by subjects in all periods of each study under fasted conditions. No serious adverse events were observed. The ratios of least square means for AUC0-t and Cmax and the affiliated 90% confidence intervals were within acceptance range recommended by PMDA. Marginal differences were observed in pharmacokinetic values of Asian Indian and Japanese volunteers. The results of these bioavailability studies indicate that the test formulation of losartan/hydrochlorothiazide 50 + 12.5 mg (EPR0001) tablets is bioequivalent to marketed Preminent® reference formulation in Asian Indian and Japanese volunteers, when administered under fasting conditions. Both test and reference formulations were well tolerated

Bioequivalence of eslicarbazepine acetate from two different sources of its active product ingredient in healthy subjects.

Science.gov (United States)

Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

2013-06-01

To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions--either a single oral tablet of MF or a single oral tablet of TBM--separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90% confidence intervals (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were within the predetermined range of 80-125%. Test/reference GMR (90% CI) for the Cmax and AUC was respectively 100% (94-109%) and 96% (94-98%) following 400 mg ESL and 100% (95-105%) and 100% (97-103%) following 800 mg ESL. Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix® formulation according to the regulatory definition of bioequivalence.

Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

KAUST Repository

Al-Talla, Zeyad; Akrawi, Sabah H.; Emwas, Abdul-Hamid M.

2011-01-01

Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a

The bootstrap and Bayesian bootstrap method in assessing bioequivalence

International Nuclear Information System (INIS)

Wan Jianping; Zhang Kongsheng; Chen Hui

2009-01-01

Parametric method for assessing individual bioequivalence (IBE) may concentrate on the hypothesis that the PK responses are normal. Nonparametric method for evaluating IBE would be bootstrap method. In 2001, the United States Food and Drug Administration (FDA) proposed a draft guidance. The purpose of this article is to evaluate the IBE between test drug and reference drug by bootstrap and Bayesian bootstrap method. We study the power of bootstrap test procedures and the parametric test procedures in FDA (2001). We find that the Bayesian bootstrap method is the most excellent.

Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

Science.gov (United States)

Ramirez, Elena; Laosa, Olga; Guerra, Pedro; Duque, Blanca; Mosquera, Beatriz; Borobia, Alberto M; Lei, Suhua H; Carcas, Antonio J; Frias, Jesus

2010-01-01

AIM The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes. METHODS We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products. RESULTS Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3. CONCLUSIONS Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for Cmax or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies. PMID:21039763

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

Science.gov (United States)

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

Bioequivalence assessment of two formulations of ibuprofen

Directory of Open Access Journals (Sweden)

Al-Talla ZA

2011-10-01

, therefore, Doloraz was considered bioequivalent to Brufen. Keywords: ibuprofen, bioequivalence study, pharmacokinetics

Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

Science.gov (United States)

Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

2016-01-01

Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Directory of Open Access Journals (Sweden)

Eunice Kazue Kano

2015-03-01

Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

Current Challenges in Bioequivalence, Quality, and Novel Assessment Technologies for Topical Products

DEFF Research Database (Denmark)

Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D

2014-01-01

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic...

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

Science.gov (United States)

Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

2013-11-01

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Significance of metabolites in bioequivalence: losartan potassium as a case study.

Science.gov (United States)

Charoo, Naseem Ahmad; Cristofoletti, Rodrigo; Khatri, Aamer Roshanali; Ali, Areeg Anwer

2014-06-01

Estimation of metabolite data as a supportive evidence of comparable therapeutic outcome is recommended by various guidance documents. However, a consensus on using it solely to establish bioequivalence (BE) is lacking as parent drug is believed to detect pharmacokinetic differences between test and reference formulations better. Four BE studies of losartan potassium reported in the literature are reviewed. In all the four studies, 90% confidence intervals (CIs) of geometric mean ratios of the test and reference formulations for maximum blood drug concentration (Cmax ) of losartan potassium were outside the acceptable range of 80%-125%, whereas, 90% CIs for its active metabolite, losartan carboxylic acid (LCA), were within the acceptance criteria. Although BE with respect to area under the plasma concentration versus time profile curve was demonstrated in all the cases, BE with respect to Cmax could not be established. However, marketing authorization in all the four cases was granted based on scientific evidence that LCA is 10-40 times more potent than losartan, LCA exhibited higher plasma concentration levels than losartan, pharmacodynamic effects correlate with LCA, and losartan shows wide therapeutic index. Further, widened CI limits for losartan were accepted. Losartan presents an opportunity in the diligence of the principles of quality risk management for selecting moiety on which BE decision must be based. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Proposing the Use of Partial AUC as an Adjunctive Measure in Establishing Bioequivalence Between Deltoid and Gluteal Administration of Long-Acting Injectable Antipsychotics.

Science.gov (United States)

Lee, Lik Hang N; Choi, Charles; Gershkovich, Pavel; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

2016-12-01

The maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC) are commonly used to establish bioequivalence between two formulations of the same oral medication. Similarly, these pharmacokinetic parameters have also been used to establish bioequivalence between two sites of administration for the same injectable formulation. However, these conventional methods of establishing bioequivalence are of limited use when comparing modified-release formulations of a drug, particularly those with rates of absorption that are amenable to change with the site of injection. Inherent differences in the rate of absorption can result in clinically significant differences in early exposure and drug response. Here, we propose the use of the partial AUC (pAUC) as a measure of early exposure to aid in the assessment of bioequivalence between the gluteal and the deltoid site of administration for long-acting injectable antipsychotics.

Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

KAUST Repository

Al-Talla, Zeyad

2011-01-01

Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

Science.gov (United States)

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

2015-03-01

RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets
.

Science.gov (United States)

Cho, Hea-Young; Ngo, Lien; Kim, Sang-Ki; Choi, Yoonho; Lee, Yong-Bok

2018-06-01

This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24 hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC0-t, AUC0-∞, and Cmax based on EDI tablets were 110.07 (102.25 - 118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively, for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and 98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated.
.

Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics

DEFF Research Database (Denmark)

Kreilgaard, Mads; Kemme, M J; Burggraaf, J

2001-01-01

The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method....

Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

Science.gov (United States)

Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

2015-06-01

Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

Development of a new benazepril hydrochloride chewable tablet and evaluation of its bioequivalence for treatment of heart failure in dogs.

Science.gov (United States)

Qian, M; Chen, T; Zhou, D; Zhang, Z; Zhang, Q; Tang, S; Xiao, X

2016-02-01

The aim of the study was to develop a new chewable benazepril hydrochloride(BH) tablet, investigate its physical properties, and evaluate its bioequivalence with the branded formulation (Fortekor). A corrective agent was included in the formula to improve its palatability and convenience for administration to dogs. The tablet remained stable in light, heat, and humidity tests, and its physical properties such as hardness, uniformity of content, and dissolution rate were highly consistent with the technical standards. After single and repeated administrations to eight beagles and single dose to 14 mongrel dogs (0.5 mg/kg p.o.), plasma BH and its active metabolite, benazeprilat (BZ), were detected. There was no significant difference in the major pharmacokinetic parameters (Cmax , Tmax, and AUC₀₋₂₄) between the two formulations. The 90% confidence intervals calculated for the ratios of area under the time-concentration curve (AUC₀₋₂₄) were 92.4-116.3% for BH and 89.9-102.3% for BZ, within the accepted range for bioequivalence of 80-125%. The results showed our new chewable tablet is bioequivalent to the commercial product and suitable for addition to the benazepril product family for the treatment of heart failure in dogs. © 2015 John Wiley & Sons Ltd.

Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

Science.gov (United States)

Stavchansky, Salomon

2008-06-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

Science.gov (United States)

Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

2008-10-01

Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel

DEFF Research Database (Denmark)

Tettey-Amlalo, Ralph Nii Okai; Kanfer, Isadore; Skinner, Michael F

2008-01-01

The purpose was to investigate dermal microdialysis (DMD) for the assessment of the bioavailability of a ketoprofen topical gel formulation and to evaluate this technique as a tool for the determination of bioequivalence. Four microdialysis probes were inserted into the dermis on the volar aspect...

Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

Science.gov (United States)

Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

2010-05-01

To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

Rapid determination of telmisartan in human plasma by HPLC using a monolithic column with fluorescence detection and its application to a bioequivalence study.

Science.gov (United States)

Zhang, He; Jiang, Yunyun; Wen, Jun; Zhou, Tingting; Fan, Guorong; Wu, Yutian

2009-11-01

A rapid HPLC method using a monolithic column with fluorescence detection has been developed for determination of telmisartan in human plasma. Sample preparation was done by protein precipitation with acetonitrile and naproxen was used as IS. The compounds were detected by fluorescence detection, using an excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high throughput, sensitive and precise, and it was successfully applied to a bioequivalence study of two formulations of telmisartan.

Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers.

Science.gov (United States)

Holt, Robert J; Taiwo, Tolu; Kent, Jeffrey D

2015-08-01

Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects. The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods. The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac. The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https

The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

Science.gov (United States)

Tsume, Yasuhiro; Amidon, Gordon L

2010-08-02

The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

Bioequivalence of a new liquid formulation of benazepril compared with the reference tablet product.

Science.gov (United States)

Kelers, K; Devi, J L; Anderson, G A; Zahra, P; Vine, J H; Whittem, T

2013-08-01

To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration. Randomised cross-over design, followed by parallel comparison. Twelve mixed-breed dogs were administered either a tablet (Group A) or liquid formulation (Group B) of benazepril orally at 0.45 mg/kg daily for 4 days. With no washout period, the dogs then received the alternative treatment at the same dose for a further 4 days. Blood samples taken prior to treatment and serially after treatment were analysed for plasma concentrations of benazepril and benazeprilat and the activity and concentration of angiotensin-converting enzyme (ACE). The calculated percentage inhibition of ACE was defined as the primary outcome variable. No statistically significant differences were found between groups A and B for any variable evaluated. The mean (± SD) percentage of ACE inhibition was 85.5 ± 7.04% for the liquid formulation and 85.9 ± 6.66% for the tablet formulation. The mean of the ratios was 1.00 (80% confidence interval 0.96-1.04). No evaluated effect term (sequence, formulation or period) had any statistical effect on any outcome variable. This study supports a conclusion that, based on pharmacodynamic response, the liquid formulation of benazepril is bioequivalent to the reference tablet formulation. Further, the lack of a sequence effect supports the switchability of these two formulations. © 2013 Australian Veterinary Association.

Scientific Perspectives on Extending the Provision for Waivers of In vivo Bioavailability and Bioequivalence Studies for Drug Products Containing High Solubility-Low Permeability Drugs (BCS-Class 3)

OpenAIRE

Stavchansky, Salomon

2008-01-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA–BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility–Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting ...

Determination of levodopa in human plasma by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS: application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Heliana F. Martins

2013-01-01

Full Text Available A sensitive, accurate and simple method using HPLC-MS/MS was developed and validated for levodopa quantitation in human plasma. Analysis was achieved on a pursuit® C18 analytical column (5 µm; 150 x 4.6 mm i.d. using a mobile phase (methanol and water , 90:10, v/v containing formic acid 0.5% v/v, after extracting the samples using a simple protein plasma precipitation with perchloric acid. The developed method was validated in accordance with ANVISA guidelines and was successfully applied to a bioequivalence study in 60 healthy volunteers demonstrating the feasibility and reliability of the proposed method.

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

Science.gov (United States)

Mita, Sachiko; Chitnis, Shripad D; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Zhou, Wei; Suzuki, Hikoe

2016-04-01

To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

Directory of Open Access Journals (Sweden)

Radicioni M

2017-04-01

Full Text Available Milko Radicioni,1 Chiara Castiglioni,1 Andrea Giori,2 Irma Cupone,3 Valeria Frangione,4 Stefano Rovati4 1CROSS Research S.A., Phase I Unit, Arzo, Switzerland; 2IBSA Farmaceutici Italia, Lodi, Italy; 3Bouty S.p.A., Strada Padana Superiore, Cassina De’ Pecchi, Italy; 4IBSA Institut Biochimique S.A., Pambio-Noranco, Switzerland Abstract: A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra® after single-dose administration to 53 healthy male volunteers (aged 18–51 years in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg

Development and validation of a liquid chromatography-tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study.

Science.gov (United States)

Ye, Ling; Shi, Jian; Wan, Shanhe; Yang, Xiaoshan; Wang, Ying; Zhang, Jiajie; Zheng, Dayong; Liu, Zhongqiu

2013-11-01

Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs. Copyright © 2013 John Wiley & Sons, Ltd.

Bioequivalence assessment of two formulations of ibuprofen

KAUST Repository

Al-Talla, Zeyad

2011-10-19

Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

Science.gov (United States)

Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

2013-03-01

Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

Determination of itopride in human plasma by liquid chromatography coupled to tandem mass spectrometric detection: application to a bioequivalence study.

Science.gov (United States)

Lee, Heon-Woo; Seo, Ji-Hyung; Choi, Seung-Ki; Lee, Kyung-Tae

2007-01-30

A simple method using a one-step liquid-liquid extraction (LLE) with butyl acetate followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of itopride in human plasma, using sulpiride as an internal standard (IS). Acquisition was performed in multiple reaction monitoring (MRM) mode, by monitoring the transitions: m/z 359.5>166.1 for itopride and m/z 342.3>111.6 for IS, respectively. Analytes were chromatographed on an YMC C18 reverse-phase chromatographic column by isocratic elution with 1 mM ammonium acetate buffer-methanol (20: 80, v/v; pH 4.0 adjusted with acetic acid). Results were linear (r2=0.9999) over the studied range (0.5-1000 ng mL(-1)) with a total analysis time per run of 2 min for LC-MS/MS. The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

Science.gov (United States)

Baribeault, David

2011-08-01

Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers

Science.gov (United States)

Radicioni, Milko; Castiglioni, Chiara; Giori, Andrea; Cupone, Irma; Frangione, Valeria; Rovati, Stefano

2017-01-01

A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an orally disintegrating film formulation and provide an alternative to the current marketed products for the treatment of erectile dysfunction. The pharmacokinetics of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the conventional marketed 100 mg film-coated tablet (Viagra®) after single-dose administration to 53 healthy male volunteers (aged 18–51 years) in a randomized, open, two-way crossover bioequivalence study. Each subject received a single oral dose of 100 mg of sildenafil as test or reference formulation administered under fasting conditions at each of the two study periods according to a randomized crossover design. There was a washout interval of ≥7 days between the two administrations of the investigational medicinal products. Blood samples for pharmacokinetic analysis were collected up to 24 h post-dosing. The primary objective was to compare the rate (peak plasma concentration; Cmax) and extent (area under the curve [AUC] from administration to last observed concentration time; AUC0–t) of sildenafil absorption after single-dose administration of test and reference. Secondary endpoints were observed to describe the plasma pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil relative bioavailability and safety profile after single-dose administration. The mean sildenafil and N-desmethyl-sildenafil plasma concentration–time profiles up to 24 h after single-dose administration of sildenafil 100 mg orodispersible film and film-coated tablet were nearly superimposable. The bioequivalence test was fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and extent of bioavailability. Adverse events occurred at similar rates for the two formulations and were of mild-to-moderate severity. The results suggest that the new orodispersible film

Quantification of sibutramine and its two metabolites in human plasma by LC–ESI-MS/MS and its application in a bioequivalence study

Directory of Open Access Journals (Sweden)

Venkata Suresh Ponnuru

2012-08-01

Full Text Available Obesity can be considered as a chronic illness of epidemic proportion and its incidents have increased exponentially in recent years. The use of anti-obesity drugs such as sibutramine is somewhat helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS method for the quantification of sibutramine (SB and its two metabolites N-des methyl sibutramine (DSB and N-di desmethyl sibutramine (DDSB in human plasma. Zorbax SB-C18 (4.6 mm×75 mm, 3.5 μm, 80 Å analytical column and 5 mM ammonium formate:acetonitrile (10:90, v/v mobile phase were used for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM in the positive mode was used to detect SB, DSB and DDSB at m/z 280.3/124.9, 266.3/125.3 and 252.2/124.9, respectively. Liquid–liquid extraction was used for the extraction of analytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0–10,000.0 pg/mL for SB, DSB and DDSB with correlation coefficients (r of ≥0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting condition. Keywords: LC–ESI-MS/MS, Sibutramine, Human plasma, Bioequivalence, Pharmacokinetic study

Improved simultaneous quantitation of candesartan and hydrochlorthiazide in human plasma by UPLC–MS/MS and its application in bioequivalence studies

Directory of Open Access Journals (Sweden)

Bhupinder Singh

2014-04-01

Full Text Available A validated ultra-performance liquid chromatography mass spectrometric method (UPLC–MS/MS was used for the simultaneous quantitation of candesartan (CN and hydrochlorothiazide (HCT in human plasma. The analysis was performed on UPLC–MS/MS system using turbo ion spray interface. Negative ions were measured in multiple reaction monitoring (MRM mode. The analytes were extracted using a liquid–liquid extraction (LLE method by using 0.1 mL of plasma volume. The lower limit of quantitation for CN and HCT was 1.00 ng/mL whereas the upper limit of quantitation was 499.15 ng/mL and 601.61 ng/mL for CN and HCT respectively. CN d4 and HCT-13Cd2 were used as the internal standards for CN and HCT respectively. The chromatography was achieved within 2.0 min run time using a C18 Phenomenex, Gemini NX (100 mm×4.6 mm, 5 µm column with organic mixture:buffer solution (80:20, v/v at a flow rate of 0.800 mL/min. The method has been successfully applied to establish the bioequivalence of candesartan cilexetil (CNC and HCT immediate release tablets with reference product in human subjects. Keywords: Candesartan cilexetil, Hydrochlorothiazide, UPLC–MS/MS, Bioequivalence, Candesartan cilexetil-hydrochlorothiazide (ATACAND HCT

Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers.

Science.gov (United States)

Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba; Nemati, Mahboob

2010-01-01

Valsartan (CAS 137862-53-4) is an antihypertensive drug belonging to the family of angiotensin II receptor antagonists acting at the AT1 receptor, which mediates all known effects of angiotensin II on the cardiovascular system. In the present study, the pharmacokinetic parameters of two oral formulations of valsartan tablets were compared in a randomized, single oral dose, two-treatment crossover design in 24 healthy male volunteers under fasting conditions. After an overnight fast, the volunteers received 80 mg valsartan. Blood samples were collected up to 48 h and drug concentrations were determined by a reverse-phase HPLC method with fluorescence detection. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The obtained values for test and reference products were 3067.7 +/- 1,281.7 and 3,304.3 +/- 1,196.4 ng/ml for Cmax; 17,834.4 +/- 7,083.8 and 18,319.1 +/- 7,800.7 ng x h/ml for AUC0-48; 18,825.7 +/- 7,553.2 and 19,172.2 +/- 8,307.2 ng x h/ml for AUC0-infinity, respectively. The 90% confidence intervals obtained by analysis of variance were 86.84-100.87% for Cmax and 93.43-115.54% for AUC0-t, which are within the acceptance range of 80-125%. Therefore it can be concluded that both products are bioequivalent in terms of rate and extent of drug absorption and therefore interchangeable.

Liquid chromatography-tandem mass spectrometry for the quantification of flurbiprofen in human plasma and its application in a study of bioequivalence.

Science.gov (United States)

Mei, Chenghan; Li, Bin; Yin, Qiangfeng; Jin, Jing; Xiong, Ting; He, Wenjuan; Gao, Xiujuan; Xu, Rong; Zhou, Piqi; Zheng, Heng; Chen, Hui

2015-07-01

A simple, quick and accurate LC-MS/MS method for the quantification of flurbiprofen in human plasma with indomethacin as internal standard (IS) was developed and validated. Samples were treated with methanol to precipitate proteins, then separated on a Ultimate C18 column (5μm, 2.1×50mm) with a gradient elusion process. Mobile phase A was comprised of water and formic acid, mobile phase B was comprised of acetonitrile and formic acid. Multi reaction monitoring (MRM) signals were saved on a negative ionization electrospray mass spectrometer. The calibration curve showed good linearity in the range of 40.00-10000.00μg/L (r(2)=0.998). Intra-day RE was 0.2-2.2%. Inter-day RE was 0.5-3.4%. The samples showed good stability under the study conditions. No significant matrix effect was observed. The established method was then applied to a bioequivalence study of a flurbiprofen axetil formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

Science.gov (United States)

Dadey, Eric

Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

Directory of Open Access Journals (Sweden)

K. O. Zupanets

2016-03-01

Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

Science.gov (United States)

Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

2009-10-01

Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

LC–MS/MS assay for olanzapine in human plasma and its application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Dinesh S. Patel

2012-10-01

Full Text Available This paper describes a selective and sensitive assay for the determination of olanzapine (OLZ in human plasma based on liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analyte and quetiapine as internal standard (IS were extracted from 200 μL plasma via solid phase extraction on Waters Oasis HLB cartridges. Chromatographic separation was achieved on an ACE 5C18-300 column (100 mm×4.6 mm, 5 μm under isocratic conditions in a run time of 3.5 min. Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring (MRM of the transitions at m/z 313/256 for OLZ and m/z 384/253 for the IS. The assay was linear in the range 0.10–40.0 ng/mL with a lower limit of quantitation and limit of detection of 0.10 and 0.012 ng/mL, respectively. Intra- and inter-day precision (as coefficient of variation and relative recovery were 90%, respectively. The method was successfully applied to a bioequivalence study of 5 and 10 mg OLZ disintegrating tablets in 40 healthy Indian males with reproducibility by incurred sample reanalysis in the range −7.43 to 8.07%.

Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

Science.gov (United States)

Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

Science.gov (United States)

Pai, Amy Barton

2017-11-01

Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

[Bioequivalence of dermatological topical medicines:the Brazilian scenario and the challenges for health surveillance].

Science.gov (United States)

Soares, Kelen Carine Costa; Moraes, Marcelo Vogler; Gelfuso, Guilherme Martins; Gratieri, Taís

2015-11-01

The comparative evaluation required for the registration of generic topical medicines in Brazil is conducted by means of a pharmaceutical equivalence study, which merely assesses the physical/chemical and microbiological parameters of the formulations. At the international level, clinical or pharmacodynamic studies are now being required to prove the efficacy and safety of semisolid topical generic formulations. This work presents a comparison of the different requirements for the registration of topical formulations, taking into consideration the various regulatory authorities, and presents a survey of topical medicines registered in Brazil prior to 2013. The survey revealed that in comparison with the USA there were many more copies of these formulations registered in Brazil. This fact, together with the large number of studies in the literature showing the lack of bioequivalence of topical medication, is clear proof of the major importance of the need to realign Brazilian legislation with respect to the technical requirements for the registration of generic and similar medication for dermatological topical application in Brazil.

Large-volume injection of sample diluents not miscible with the mobile phase as an alternative approach in sample preparation for bioanalysis: an application for fenspiride bioequivalence.

Science.gov (United States)

Medvedovici, Andrei; Udrescu, Stefan; Albu, Florin; Tache, Florentin; David, Victor

2011-09-01

Liquid-liquid extraction of target compounds from biological matrices followed by the injection of a large volume from the organic layer into the chromatographic column operated under reversed-phase (RP) conditions would successfully combine the selectivity and the straightforward character of the procedure in order to enhance sensitivity, compared with the usual approach of involving solvent evaporation and residue re-dissolution. Large-volume injection of samples in diluents that are not miscible with the mobile phase was recently introduced in chromatographic practice. The risk of random errors produced during the manipulation of samples is also substantially reduced. A bioanalytical method designed for the bioequivalence of fenspiride containing pharmaceutical formulations was based on a sample preparation procedure involving extraction of the target analyte and the internal standard (trimetazidine) from alkalinized plasma samples in 1-octanol. A volume of 75 µl from the octanol layer was directly injected on a Zorbax SB C18 Rapid Resolution, 50 mm length × 4.6 mm internal diameter × 1.8 µm particle size column, with the RP separation being carried out under gradient elution conditions. Detection was made through positive ESI and MS/MS. Aspects related to method development and validation are discussed. The bioanalytical method was successfully applied to assess bioequivalence of a modified release pharmaceutical formulation containing 80 mg fenspiride hydrochloride during two different studies carried out as single-dose administration under fasting and fed conditions (four arms), and multiple doses administration, respectively. The quality attributes assigned to the bioanalytical method, as resulting from its application to the bioequivalence studies, are highlighted and fully demonstrate that sample preparation based on large-volume injection of immiscible diluents has an increased potential for application in bioanalysis.

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

Science.gov (United States)

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

Estudio de bioequivalencia de clonazepam, tabletas de 2 mg, en voluntarios sanos colombianos Bioequivalence study of clonazepam 2 mg tablets in colombian healthy volunteers

Directory of Open Access Journals (Sweden)

Victoria Eugenia Toro Pareja

2007-08-01

Full Text Available Con el fin de determinar la bioequivalencia de dos formulaciones de tabletas de 2 mg de clonazepam: Sedatril®/Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia como producto de prueba y Rivotril® (Roche Químicos e Farmacéuticas S. A., Río de Janeiro, Brasil, como producto de referencia, se realizó un estudio de bioequivalencia en 26 voluntarios sanos. Los productos de prueba y de referencia se administraron en condiciones de ayuno de acuerdo con un diseño cruzado aleatorio de dosis única, con dos secuencias, dos tratamientos y un período de lavado de 28 días. Las muestras de sangre se obtuvieron desde las 0 hasta las 96 horas después de la administración del medicamento. Los niveles plasmáticos de clonazepam se determinaron con un método validado por cromatografía líquida de alta eficiencia con detección ultravioleta (HPLC/UV, siglas en inglés. Los parámetros farmacocinéticos ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke se determinaron de los perfiles plasmáticos concentración-tiempo por el método no compartimental. El test de bioequivalencia se realizó con los datos transformados a logaritmo natural (ln de ABC0-∞and Cmax. Los intervalos de confianza del 90% para la relación producto de prueba/producto de referencia fueron de 87,9% a 103,6% y 84,4% a 104,0%, respectivamente. Estos resultados estuvieron dentro de los rangos de aceptación del 80,0% al 125%, establecidos por la FDA y se concluyó que ambos productos son bioequivalentes. In order to determine the bioequivalence of two formulations of clonazepam 2 mg tablets: Sedatril®/ Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia as a test product and Rivotril® (Roche Químicos e Farmacêuticas S. A., Rio de Janeiro, Brazil as a reference product, a bioavailability study was performed in 26 healthy volunteers. Test and reference products were administered under fasting conditions following a single dose, two-sequences, two treatments, crossover randomized

Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex absorption: methylphenidate.

Science.gov (United States)

Fourie Zirkelbach, Jeanne; Jackson, Andre J; Wang, Yaning; Schuirmann, Donald J

2013-01-01

Methylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products. A two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC. The sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased. PAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted.

Determination of torasemide in human plasma and its bioequivalence study by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Lin Zhang

2016-04-01

Full Text Available A sensitive and selective method using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS to determine the concentration of torasemide in human plasma samples was developed and validated. Tolbutamide was chosen as the internal standard (IS. The chromatography was performed on a Gl Sciences Inertsil ODS-3 column (100 mm×2.1 mm i.d., 5.0 µm within 5 min, using methanol with 10 mM ammonium formate (60:40, v/v as mobile phase at a flow rate of 0.2 mL/min. The targeted compound was detected in negative ionization at m/z 347.00 for torasemide and 269.00 for IS. The linearity range of this method was found to be within the concentration range of 1–2500 ng/mL (r=0.9984 for torasemide in human plasma. The accuracy of this measurement was between 94.05% and 103.86%. The extracted recovery efficiency was from 84.20% to 86.47% at three concentration levels. This method was also successfully applied in pharmacokinetics and bioequivalence studies in Chinese volunteers.

Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid.

Science.gov (United States)

Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

2015-07-10

The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

Science.gov (United States)

Brendel, Erich; Weimann, Boris; Dietrich, Hartmut; Froede, Christoph; Thomas, Dirk

2013-09-01

To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs. 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method. Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated. The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.

Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.

Science.gov (United States)

Ma, Jing; Yuan, Li-Hua; Ding, Mei-Juan; Zhang, Jun; Zhang, Qing; Xu, Qun-Wei; Zhou, Xue-Min

2009-03-01

A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

Development and validation of an improved method for the quantitation of sertraline in human plasma using LC-MS-MS and its application to bioequivalence studies.

Science.gov (United States)

Zhang, Mengliang; Gao, Feng; Cui, Xiangyong; Zhang, Yunhui; Sun, Yantong; Gu, Jingkai

2011-02-01

A rapid and sensitive LC-MS-MS method for the quantitation of sertraline in human plasma was developed and validated. Sertraline and the internal standard, telmisartan, were cleaned up by protein precipitation from 100 μL of plasma sample, and analyzed on a TC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 70% acetonitrile and 30% 10 mM ammonium acetate (0.1% formic acid) as mobile phase. The method was demonstrated to be linear from 0.1 ng/mL to 50 ng/mL with the lower limit of quantitation of 0.1 ng/mL. Intra- and inter-day precision were below 4.40% and 3.55%. Recoveries of sertraline at low, medium, and high levels were 88.0 ± 2.3%, 88.2 ± 1.9%, and 90.0 ± 2.0%, respectively. The method was successfully applied to a bioequivalence study of sertraline after a single oral administration of 50 mg sertraline hydrochloride tablets.

Estudio de bioequivalencia: formulaciones genéricas y comerciales de estaduvine, lamiduvine, zidovudine e indinavir en pacientes cubanos infectados con VIH Bioequivalence study: generic and trade formulations of stavudine, lamivudine, zidovudine and indinavir in Cuban HIV-infected subjects

Directory of Open Access Journals (Sweden)

Alicia Tarinas Reyes

2006-08-01

Full Text Available Objetivo: El presente estudio describe los estudios de bioequivalencia de los genéricos cubanos antirretrovirales estavudina, lamivudina, zidovudina e indinavir con respecto a sus productos innovadores. Diseño: Los estudios de bioequivalencia de cada antirretroviral estudiado (formulación de prueba, P y referencia, R, se realizaron en 13 ó 14 sujetos, según el caso con la utilización de las medias en un estudio aleatorio, cruzado y a dosis única con un período de lavado de 10 días. Métodos: Las concentración de los antirretrovirales en plasma se monitorearon durante un período de 12 h después de la administración de estos, mediante el uso de métodos validados de cromatografía líquida de alta resolución (HPLC. Los parámetros farmacocinéticos se determinaron con el uso el software profesional WinNolin, versión 2.1. La comparación de los parámetros farmacocinéticos se realizó con un intervalo de confianza del 95 % con la utilización del software NCSS 2000 PASS 2000 (hipótesis nula. Para el estudio de bioequivalencia se usó el software Equiv Test de soluciones estadísticas, empleando ANOVA con el 90 % de intervalo de confianza. Resultados: El presente estudio mostró que no se observaron diferencias significativas en las medias de AUC0-12, AUC0-¥, Cmax y Tmax de ambas formulaciones de estavudina, lamivudina, zidovudina e indinavir. Se concluye que los parámetros farmacocinéticos estudiados se encuentran dentro de los rangos establecidos siendo 80-125 % para Cmax, AUC0-12, y AUC0-¥. En el caso de Cmax de la zidovudina el rango fue 70-143 %. Conclusión: Estos resultados avalan que los genéricos antirretrovirales cubanos son bioequivalentes con sus respectivos productos innovadores en términos de velocidad y magnitud de la absorciónObjective: The present study describes the determination of the bioequivalence of the Cuban generic and trade formulations of stavudine, lamivudine, zidovudine, and indinavir. Design: The

Quantification of amlodipine and atorvastatin in human plasma by UPLC-MS/MS method and its application to a bioequivalence study.

Science.gov (United States)

Rezk, Mamdouh R; Badr, Kamal A

2018-07-01

A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for the determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC BEH C 18 (50 × 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 mL/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.1-10 ng/mL for AML and 0.05-50 ng/mL for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of <1.5 min, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers. Copyright © 2018 John Wiley & Sons, Ltd.

Investigation of Bioequivalence Between Brand-name and Generic Irinotecan Products.

Science.gov (United States)

Saito, Ken-Ichi; Inoue, Yutaka; Ikegami, Yoji; Nanbo, Izumi; Onozuka, Mari; Sano, Kazumi; Yoshida, Hisahiro; Sakamoto, Toshihiro; Tatebayashi, Emi; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Kitazawa, Takaki

2016-11-01

To investigate bioequivalence among generic and brand-name irinotecan products. Products of Yakult and Daiichi-Sankyo (brand-name products), Sandoz, Nippon Kayaku, Taiho, and Sawai were compared with respect to their composition and antitumor activity. High-performance liquid chromatography demonstrated that related substances were within the acceptable range. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed significant differences in cytotoxicity for four cancer cell lines among the products. The concentration of the active compound SN-38 was highest in Yakult's product (23.82 ng/ml) and lowest in Daiichi-Sankyo's product (8.96 ng/ml). MTT assay data were correlated with the SN-38 concentration, suggesting that it influenced differences in cytocidal activity among products. However, the SN-38 concentration was far lower than that of irinotecan (20 mg/ml), suggesting a negligible clinical effect. Metabolism of irinotecan to SN-38 or open-ring forms did not differ significantly among the products. The generic products showed equivalent efficacy and safety to the brand-name products. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Advantages of automation in plasma sample preparation prior to HPLC/MS/MS quantification: application to the determination of cilazapril and cilazaprilat in a bioequivalence study.

Science.gov (United States)

Kolocouri, Filomila; Dotsikas, Yannis; Apostolou, Constantinos; Kousoulos, Constantinos; Soumelas, Georgios-Stefanos; Loukas, Yannis L

2011-01-01

An HPLC/MS/MS method characterized by complete automation and high throughput was developed for the determination of cilazapril and its active metabolite cilazaprilat in human plasma. All sample preparation and analysis steps were performed by using 2.2 mL 96 deep-well plates, while robotic liquid handling workstations were utilized for all liquid transfer steps, including liquid-liquid extraction. The whole procedure was very fast compared to a manual procedure with vials and no automation. The method also had a very short chromatographic run time of 1.5 min. Sample analysis was performed by RP-HPLC/MS/MS with positive electrospray ionization using multiple reaction monitoring. The calibration curve was linear in the range of 0.500-300 and 0.250-150 ng/mL for cilazapril and cilazaprilat, respectively. The proposed method was fully validated and proved to be selective, accurate, precise, reproducible, and suitable for the determination of cilazapril and cilazaprilat in human plasma. Therefore, it was applied to a bioequivalence study after per os administration of 2.5 mg tablet formulations of cilazapril.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

Science.gov (United States)

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-06-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

Directory of Open Access Journals (Sweden)

André Daher

2015-06-01

Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.

Science.gov (United States)

van Gelder, Teun; Gabardi, Steven

2013-08-01

Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

Science.gov (United States)

2010-04-01

... vivo bioavailability study. 320.27 Section 320.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.27...

Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

Science.gov (United States)

Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

2015-12-07

In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

Science.gov (United States)

Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

2017-08-01

On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Preparation and Comparative Bioavailability Studies of Indomethacin-Loaded Cetyl Alcohol Microspheres

Directory of Open Access Journals (Sweden)

N. Vishal Gupta

2013-01-01

Full Text Available The purpose of the present study was to compare the in vitro release and to find out whether the bioavailability of a 75 mg indomethacin capsule (Microcid SR was equivalent to optimized formulation (indomethacin-loaded cetyl alcohol microspheres. Indomethacin-loaded cetyl alcohol microspheres were prepared by meltable emulsified cooling-induced technique. Surface morphology of microspheres has been evaluated using scanning electron microscopy. A single dose, randomized, complete cross over study of IM microspheres was carried out on 10 healthy male and female Albino sheep’s under fasting conditions. The plasma was separated and the concentrations of the drug were determined by HPLC-UV method. Plasma indomethacin concentrations and other pharmacokinetic parameters obtained were statistically analyzed. The SEM images revealed the spherical shape of fat microspheres, and more than 98.0% of the isolated microspheres were in the size range 12–32 μm. DSC, FTIR spectroscopy and stability studies indicated that the drug after encapsulation with fat microspheres was stable and compatible. Both formulations were found to be bioequivalent as evidenced by in vivo studies. Based on this study, it can be concluded that cetyl alcohol microspheres and Microcid SR capsule are bioequivalent in terms of the rate and extent of absorption.

Comparison of parametric and bootstrap method in bioequivalence test.

Science.gov (United States)

Ahn, Byung-Jin; Yim, Dong-Seok

2009-10-01

The estimation of 90% parametric confidence intervals (CIs) of mean AUC and Cmax ratios in bioequivalence (BE) tests are based upon the assumption that formulation effects in log-transformed data are normally distributed. To compare the parametric CIs with those obtained from nonparametric methods we performed repeated estimation of bootstrap-resampled datasets. The AUC and Cmax values from 3 archived datasets were used. BE tests on 1,000 resampled datasets from each archived dataset were performed using SAS (Enterprise Guide Ver.3). Bootstrap nonparametric 90% CIs of formulation effects were then compared with the parametric 90% CIs of the original datasets. The 90% CIs of formulation effects estimated from the 3 archived datasets were slightly different from nonparametric 90% CIs obtained from BE tests on resampled datasets. Histograms and density curves of formulation effects obtained from resampled datasets were similar to those of normal distribution. However, in 2 of 3 resampled log (AUC) datasets, the estimates of formulation effects did not follow the Gaussian distribution. Bias-corrected and accelerated (BCa) CIs, one of the nonparametric CIs of formulation effects, shifted outside the parametric 90% CIs of the archived datasets in these 2 non-normally distributed resampled log (AUC) datasets. Currently, the 80~125% rule based upon the parametric 90% CIs is widely accepted under the assumption of normally distributed formulation effects in log-transformed data. However, nonparametric CIs may be a better choice when data do not follow this assumption.

Operating characteristics of a partial-block randomized crossover bioequivalence study for dutasteride, a drug with a long half-life: investigation through simulation and comparison with final results.

Science.gov (United States)

Cai, Gengqian; Thiessen, Jake J; Baidoo, Charlotte A; Fossler, Michael J

2010-10-01

Studies to establish bioequivalence (BE) of a drug are important elements in support of drug applications. A typical BE study is conducted as a single dose, randomized, 2-period crossover design. For drugs with long half lives (≥ 48 hours) and evaluation of multiple BE objectives in 1 trial, this design may not be adequate. A parallel design may then be a more appropriate choice. However, parallel designs require increased sample size, which can become substantial. One option that is a compromise between the complete randomized block design and the parallel design is a partial-block crossover design. This approach came about during the development of a combination of dutasteride and tamsulosin. Previous experience with performing single-dose dutasteride studies suggested that 28 days of washout is needed between treatments because of its half-life of 7-9 days. Simulations were performed to assess the operating characteristics of this design using a previously developed PK model. Four scenarios were developed, and each scenario was simulated 500 times. The results showed that this design demonstrated acceptable consumer and producer risk. Partial-block crossover designs should be considered for studies when the half-life of the drug is long and there are more than 2 periods.

SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women

Directory of Open Access Journals (Sweden)

Pravin G. Vanol

2016-08-01

Full Text Available A rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm column using methanol-0.1% formic acid in water (85:15, v/v as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10–100 ng/mL (r2≥0.9990 using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR of 74 subject samples.

Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

Science.gov (United States)

Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

2013-10-01

To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

Simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: application to a bioequivalence study.

Science.gov (United States)

Hu, Ziyan; Zou, Qiaogen; Tian, Jixin; Sun, Lili; Zhang, Zunjian

2011-12-15

A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 μm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantitation of itopride in human serum by high-performance liquid chromatography with fluorescence detection and its application to a bioequivalence study.

Science.gov (United States)

Singh, Sonu Sundd; Jain, Manish; Sharma, Kuldeep; Shah, Bhavin; Vyas, Meghna; Thakkar, Purav; Shah, Ruchy; Singh, Shriprakash; Lohray, Brajbhushan

2005-04-25

A new method was developed for determination of itopride in human serum by reversed phase high-performance liquid chromatography (HPLC) with fluorescence detection (excitation at 291 nm and emission at 342 nm). The method employed one-step extraction of itopride from serum matrix with a mixture of tert-butyl methyl ether and dichloromethane (70:30, v/v) using etoricoxib as an internal standard. Chromatographic separation was obtained within 12.0 min using a reverse phase YMC-Pack AM ODS column (250 mm x 4.6 mm, 5 microm) and an isocratic mobile phase constituting of a mixture of 0.05% tri-fluoro acetic acid in water and acetonitrile (75:25, v/v) flowing at a flow rate of 1.0 ml/min. The method was linear in the range of 14.0 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 14.0 ng/ml. Average recovery of itopride and the internal standard from the biological matrix was more than 66.04 and 64.57%, respectively. The inter-day accuracy of the drug containing serum samples was more than 97.81% with a precision of 2.31-3.68%. The intra-day accuracy was 96.91% or more with a precision of 5.17-9.50%. Serum samples containing itopride were stable for 180.0 days at -70+/-5 degrees C and for 24.0 h at ambient temperature (25+/-5 degrees C). The method was successfully applied to the bioequivalence study of itopride in healthy, male human subjects.

Application of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of bumetanide in human plasma for a bioequivalence study.

Science.gov (United States)

Patel, Dinesh S; Sharma, Naveen; Patel, Mukesh C; Patel, Bhavin N; Shrivastav, Pranav S; Sanyal, Mallika

2012-07-01

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of bumetanide in human plasma using tamsulosin as internal standard (IS). The analyte and IS were extracted from 200 μL of human plasma via solid phase extraction and the chromatographic separation was achieved on Peerless Basic C18 (100 mm × 4.6 mm, 3 μm) column under isocratic conditions. Detection of bumetanide and IS was done by tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for bumetanide and IS were m/z 365.2→240.2 and 409.2→228.2 respectively. The method was fully validated as per the US FDA guidelines. The limit of detection and lower limit of quantitation of the method were 0.03 and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for bumetanide. The intra-batch and inter-batch precision (% CV) was ≤6.9% while the mean extraction recovery was >90% across quality control levels. The method is selective in presence of four diuretic drugs and some commonly used medications by healthy volunteers. It was successfully applied to a bioequivalence study of 2mg bumetanide tablet formulation in 10 healthy Indian male subjects under fasting condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 42 incurred samples. Copyright © 2012 Elsevier B.V. All rights reserved.

The free fractions of circulating docosahexaenoic acid and eicosapentenoic acid as optimal end-point of measure in bioavailability studies on n-3 fatty acids.

Science.gov (United States)

Scarsi, Claudia; Levesque, Ann; Lisi, Lucia; Navarra, Pierluigi

2015-05-01

The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

A simple and sensitive HPLC method for analysis of imipramine in human plasma with UV detection and liquid-liquid extraction: Application in bioequivalence studies.

Science.gov (United States)

Rezazadeh, Mahboubeh; Emami, Jaber

2016-01-01

High-performance liquid chromatography (HPLC) methods employing ultraviolet (UV) detector are not sufficiently sensitive to measure the low plasma concentrations following single oral dose of imipramine. Therefore, in the present study a simple, rapid and yet sensitive HPLC method with UV detection was developed and validated for quantitation of imipramine in human plasma samples. An efficient liquid-liquid extraction (LLE) of imipramine from plasma with the mixture of hexane/isoamyl alcohol (98:2) and back extraction of the drug in acidic medium concomitant with evaporation of organic phase allowed the use of UV detector to conveniently measure plasma levels of this compound as low level as 3 ng/ml. Separation was achieved on a μ-Bondapak C18 HPLC column using sodium hydrogen phosphate solution (0.01 M)/acetonitrile (60/40 v/v) at pH 3.5 ± 0.1 at 1.5 ml/min. Trimipramine was used as the internal standard for analysis of plasma samples. The retention times for imipramine and trimipramine were 4.3 and 5.2 min, respectively. Calibration curve was linear in the range of 3-40 ng/ml using human plasma with the average extraction recovery of 85 ± 5%. Imipramine was found to be stable in plasma samples with no evidence of degradation during three freeze-thaw cycles and three months storage at -70°C. The current validated method was finally applied in bioequivalence studies of two different imipramine products according to a standard two-way crossover design with a two weeks washout period.

Determination of bioequivalence of lomefloxacin tablets using urinary excretion data.

Science.gov (United States)

Shah, Shailesh A; Rathod, Ishwarsinh S; Savale, Shrinivas S; Patel, Dharmesh B

2002-11-07

The present study describes development of a sensitive and simple HPTLC method for estimation of lomefloxacin (LMF) in human urine. The drug was extracted using chloroform after adjusting the pH of urine to 7.0. Chloroform extract was spotted on silica gel 60 F(254) TLC plate and was developed in a mixture of n-butanol-methanol-ethyl acetate-6 M ammonia (4:2:3:2, v/v/v/v) as the mobile phase and scanned at 290 nm. The peak for LMF resolved at R(F) of 0.40+/-0.02. The method was validated in terms of linearity (50-600 microgram/ml), precision, specificity and accuracy. The limit of detection and limit of quantification for LMF in urine were found to be 20 and 50 microgram/ml, respectively. The average recovery of LMF from urine was 91.93%. The proposed method was applied to generate urinary excretion data for LMF after administration of two market LMF tablet formulations (400 mg, Formulation R and Formulation T) to six healthy human volunteers in a two-treatment, open, crossover design. Various pharmacokinetic parameters like peak excretion rate ((dAU/dt)(max)), time for peak excretion rate (t(max)), AUC(0-48), AUC(0- infinity ), cumulative amount and % cumulative amount of LMF excreted, elimination half-life (t(1/2)), terminal elimination rate constant (k(el)) and overall elimination rate constant (K), were calculated for both the formulations. The average cumulative amounts of LMF excreted in urine after administration of Formulation R and Formulation T were found to be 321.60 mg (80.40% of dose) and 296.51 mg (74.13% of dose), respectively. The urinary excretion profiles of LMF upto 48 h for both the formulations were found to be similar. Statistical comparison (90% confidence intervals of ratio) of various pharmacokinetic parameters of Formulation T with that of Formulation R revealed that Formulation T is bioequivalent with Formulation R.

Application of an LC–MS/MS method for the analysis of amlodipine, valsartan and hydrochlorothiazide in polypill for a bioequivalence study

Directory of Open Access Journals (Sweden)

Jaivik V. Shah

2017-10-01

Full Text Available A sensitive and selective method has been proposed for the simultaneous determination of amlodipine (AML, valsartan (VAL and hydrochlorothiazide (HCTZ in human plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analytes and their deuterated analogs were quantitatively extracted from 100 µL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18e (100 mm × 4.6 mm analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively, under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/mL for AML, 5.00–10,000 ng/mL for VAL and 0.20–200 ng/mL for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision (% CV across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation (test and reference in 18 healthy Indian males under fasting. The mean log-transformed ratios of Cmax, AUC0–120h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

Directory of Open Access Journals (Sweden)

Mona Zarifpour

2017-05-01

Full Text Available Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI. Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume, consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

Science.gov (United States)

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

Science.gov (United States)

Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

2013-11-01

The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 μl of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. Copyright © 2013 Elsevier B.V. All rights reserved.

Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment.

Science.gov (United States)

Oishi, Masayo; Chiba, Koji; Fukushima, Takashi; Tomono, Yoshiro; Suwa, Toshio

2012-01-01

In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be ≥80% despite AUClast/AUCinf being AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug.

Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w).

Science.gov (United States)

Mitra, Amitava; Kim, Nanhye; Spark, Darren; Toner, Frank; Craig, Susan; Roper, Clive; Meyer, Thomas A

2016-12-01

The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream. Copyright © 2016 Elsevier Inc. All rights reserved.

Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

Energy Technology Data Exchange (ETDEWEB)

Szebeni, Janos, E-mail: jszebeni2@gmail.com [Nanomedicine Research and Education Center, Semmelweis University, Budapest & SeroScience Ltd, Budapest (Hungary); Storm, Gert [Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht (Netherlands)

2015-12-18

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

International Nuclear Information System (INIS)

Szebeni, Janos; Storm, Gert

2015-01-01

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

Determination of ergocalciferol in human plasma after Diels-Alder derivatization by LC–MS/MS and its application to a bioequivalence study

Directory of Open Access Journals (Sweden)

Pritesh Contractor

2017-12-01

Full Text Available An accurate, sensitive and selective method is developed for determination of ergocalciferol (vitamin D2 in human plasma using LC–MS/MS. After liquid-liquid extraction with n-hexane, ergocalciferol was derivatized by reacting with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH C18 (100 mm×4.6 mm, 2.5 µm column using acetonitrile and 0.1% (v/v formic acid in water containing 0.14% methylamine within 6.0 min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring (MRM. Entire data processing was done using Watson LIMS™ software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity (0.10 ng/mL, superior extraction efficiency (≥83% and small sample volume (100 µL for processing. The method was linear in the concentration range of 0.10–100 ng/mL for ergocalciferol. The intra-batch and inter-batch accuracy and precision (% CV values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25 mg ergocalciferol capsules in 12 healthy subjects. Keywords: Ergocalciferol, Diels-Alder reaction, 4-phenyl-1,2,4-triazoline-3,5-dione, LC–MS/MS, Human plasma

Oblique electron cyclotron emission for electron distribution studies (invited)

International Nuclear Information System (INIS)

Preische, S.; Efthimion, P.C.; Kaye, S.M.

1997-01-01

Electron cyclotron emission (ECE) at an oblique angle to the magnetic field provides a means of probing the electron distribution function both in energy and physical space through changes in and constraints on the relativistic electron cyclotron resonance condition. Diagnostics based on this Doppler shifted resonance are able to study a variety of electron distributions through changes in the location of the resonance in physical or energy space accomplished by changes in the viewing angle and frequency, and the magnetic field. For the case of observation across a changing magnetic field, such as across the tokamak midplane, the constraint on the resonance condition for real solutions to the dispersion relation can constrain the physical location of optically thin emission. A new Oblique ECE diagnostic was installed and operated on the PBX-M tokamak for the study of energetic electrons during lower hybrid current drive. It has a view 33 degree with respect to perpendicular in the tokamak midplane, receives second harmonic X-mode emission, and is constrained to receive single pass emission by SiC viewing dumps on the tokamak walls. Spatial localization of optically thin emission from superthermal electrons (50 endash 100 keV) was obtained by observation of emission upshifted from a thermal cyclotron harmonic. The localized measurements of the electron energy distribution and the superthermal density profile made by this diagnostic demonstrate its potential to study the spatial transport of energetic electrons on fast magnetohydrodynamic time scales or anomalous diffusion time scales. Oblique ECE can also be used to study electron distributions that may have a slight deviation from a Maxwellian by localizing the emission in energy space. (Abstract Truncated)

Study of single-electron excitations by electron microscopy

International Nuclear Information System (INIS)

Craven, A.J.; Gibson, J.M.; Howie, A.; Spalding, D.R.

1978-01-01

The inelastic scattering of fast electrons by the excitation of L-shell electrons at a stacking fault in silicon has been studied with a scanning transmission electron microscope. It was found that the bright-field stacking fault contrast is preserved in the filtered L-shell-loss signal at 100 eV. This result is discussed in terms of the delocalization of the excitation mechanism. It is concluded that localization effects will typically become significant only for energy transfers greater than 1 keV from a fast electron of energy 80 keV. (author)

Studying electron-PAG interactions using electron-induced fluorescence

Science.gov (United States)

Narasimhan, Amrit; Grzeskowiak, Steven; Ostrander, Jonathan; Schad, Jonathon; Rebeyev, Eliran; Neisser, Mark; Ocola, Leonidas E.; Denbeaux, Gregory; Brainard, Robert L.

2016-03-01

In extreme ultraviolet (EUV) lithography, 92 eV photons are used to expose photoresists. Typical EUV resists are organic-based and chemically amplified using photoacid generators (PAGs). Upon exposure, PAGs produce acids which catalyze reactions that result in changes in solubility. In EUV lithography, photo- and secondary electrons (energies of 10- 80 eV) play a large role in PAG acid-production. Several mechanisms for electron-PAG interactions (e.g. electron trapping, and hole-initiated chemistry) have been proposed. The aim of this study is to explore another mechanism - internal excitation - in which a bound PAG electron can be excited by receiving energy from another energetic electron, causing a reaction that produces acid. This paper explores the mechanism of internal excitation through the analogous process of electron-induced fluorescence, in which an electron loses energy by transferring that energy to a molecule and that molecule emits a photon rather than decomposing. We will show and quantify electron-induced fluorescence of several fluorophores in polymer films to mimic resist materials, and use this information to refine our proposed mechanism. Relationships between the molecular structure of fluorophores and fluorescent quantum yield may aid in the development of novel PAGs for EUV lithography.

Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

Directory of Open Access Journals (Sweden)

Jing-Bo Peng

2014-01-01

Full Text Available A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA in human plasma. Acitretin was used as the internal standard (IS. After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE, ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999 with a lower limit of quantitation (LLOQ of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers.

Molecular studies by electron spectroscopy

International Nuclear Information System (INIS)

Hansteen, J.M.

1977-01-01

Experience gained in experimental nuclear physics has played a large role in the development of electron spectroscopy as a powerful tool for studying chemical systems. The use of ESCA (Electron Spectroscopy for Chemical Analysis) for the mapping of molecular properties connected with inner as well as outer electron shells is reviewed, mainly from a phenomological point of view. Molecular Auger electron spectroscopy is described as a means of gaining information on details in molecular structure, simultaneously being extensively applied for surface studies. Future highly promising research areas for molecular electron spectroscopy are suggested to be (e,2e) processes as well as continued exploitation of synchrotron radiation from high energy nuclear devices. (Auth.)

[Role of food interaction pharmacokinetic studies in drug development. Food interaction studies of theophylline and nifedipine retard and buspirone tablets].

Science.gov (United States)

Drabant, S; Klebovich, I; Gachályi, B; Renczes, G; Farsang, C

1998-09-01

Due to several mechanism, meals may modify the pharmacokinetics of drug products, thereby eliciting to clinically significant food interaction. Food interactions with the drug substance and with the drug formulation should be distinguished. Food interaction of different drug products containing the same active ingredient can be various depending on the pharmaceutical formulation technology. Particularly, in the case of modified release products, the food/formulation interaction can play an important role in the development of food interaction. Well known example, that bioavailability of theophylline can be influenced in different way (either increased, decreased or unchanged) by concomitant intake of food in the case of different sustained release products. The role and methods of food interaction studies in the different kinds of drug development (new chemical entity, modified release products, generics) are reviewed. Prediction of food effect response on the basis of the physicochemical and pharmacokinetic characteristics of the drug molecule or formulations is discussed. The results of three food interaction studies carried out the products of EGIS Pharmaceuticals Ltd. are also reviewed. The pharmacokinetic parameters of theophyllin 400 mg retard tablet were practically the same in both fasting condition and administration after consumption of a high fat containing standard breakfast. The ingestion of a high fat containing breakfast, increased the AUC of nifedipine from 259.0 +/- 101.2 ng h/ml to 326.7 +/- 122.5 ng h/ml and Cmax from 34.5 +/- 15.9 ng/ml to 74.3 +/- 23.9 ng/ml in case of nifedipine 20 mg retard tablet, in agreement with the data of literature. The statistical evaluation indicated significant differences between the pharmacokinetic parameters in the case of two administrations (before and after meal). The effect of a high fat containing breakfast for a generic version of buspiron 10 mg tablet and the bioequivalence after food consumption were

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

Science.gov (United States)

Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

2009-03-01

Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

Social Studies by Electronic Mail.

Science.gov (United States)

Barr, Hugh

1994-01-01

Asserts that electronic mail provides opportunities to engage students actively in cross-cultural contact with students in other nations. Discusses advantages and problems with using electronic mail in the social studies classroom. Describes electronic mail projects that link students in New Zealand, England, and the United States. (CFR)

Feasibility study for mega-electron-volt electron beam tomography.

Science.gov (United States)

Hampel, U; Bärtling, Y; Hoppe, D; Kuksanov, N; Fadeev, S; Salimov, R

2012-09-01

Electron beam tomography is a promising imaging modality for the study of fast technical processes. But for many technical objects of interest x rays of several hundreds of keV energy are required to achieve sufficient material penetration. In this article we report on a feasibility study for fast electron beam computed tomography with a 1 MeV electron beam. The experimental setup comprises an electrostatic accelerator with beam optics, transmission target, and a single x-ray detector. We employed an inverse fan-beam tomography approach with radiographic projections being generated from the linearly moving x-ray source. Angular projections were obtained by rotating the object.

Electron microscope studies

International Nuclear Information System (INIS)

Crewe, A.V.; Kapp, O.H.

1990-01-01

Our laboratory has made significant progress this year in devising improved electron-optical systems, in studying invertebrate hemoglobins with the STEM, and in achieving a workable sub-angstrom STEM. Our goal in electron optics is to improve resolution by producing spherical and chromatic aberration coefficients with signs opposite those of magnetic lenses. We have progressed toward this goal through calculations that explore the addition of electrodes to electron mirrors to reduce these two geometric aberrations and by devising a beam separation system that won't introduce asymmetrical aberrations. Some promising new designs of magnetic lenses for SEM applications have also been investigated. We have continued our exploration of the quaternary structure of the invertebrate hemoglobins and are now among the top laboratories in this area of expertise. In addition, we have overcome many of our electronic difficulties on the sub-angstrom STEM and have made significant progress toward achieving an operational system. The addition of an IBM RISC-6000 workstation to our lab has significantly increased our image processing capabilities

Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

Science.gov (United States)

Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

2002-10-01

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Electronic study books and learning style

NARCIS (Netherlands)

de Diana, I.P.F.; van der Heiden, G.

1994-01-01

Attention has been drawn to the concepts of Electronic Books and Electronic Study Books. Several publications have discussed some main ideas (paradigms) for both concepts. For the Electronic Study Book as a learning environment, it is essential to consider individual modes of learning, usually

Secondary mineralization in carious lesions of human dentin. Electron-probe, electron microscope, and electron diffraction studies

Energy Technology Data Exchange (ETDEWEB)

Ogiwara, H [Tokyo Dental Coll. (Japan)

1975-02-01

Dentinal carious lesions having a remineralized surface layer were studied by means electron-probe microanalysis, electron microscopy, electron diffraction. As the results of electron-probe study, F, Mg, and Na were found to be distributed mainly in the remineralized surface layer and S in the decalcified region where decreases in Ca, P, and Mg concentration were usually observed. The decrease in Mg concentration always started earlier than that of Ca and P concentration. Electron microscope and electron diffraction studies revealed that apatic crystals in the remineralized surface layer were much larger than those in the intact dentin. Although they were less conspicuous, crystals in the decalcified region also were larger than those in the intact region. Dentinal tubules, occluded by many crystals, were frequently seen during the observations. Crystals in the tubules varied in morphology, showing granular, needle, rhomboid, and tabular shapes. By means of electron diffraction, the granular- or needle-shaped crystals were identified as apatite and the rhomboid-shaped crystals as whitlockite. Some of the tabular-shaped crystals appeared to be cotacalcium phosphate.

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

Science.gov (United States)

Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

2018-01-01

A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

Science.gov (United States)

Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

2016-03-01

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

Science.gov (United States)

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

Monte Carlo study of electron relaxation in graphene with spin polarized, degenerate electron gas in presence of electron-electron scattering

Science.gov (United States)

Borowik, Piotr; Thobel, Jean-Luc; Adamowicz, Leszek

2017-12-01

The Monte Carlo simulation method is applied to study the relaxation of excited electrons in monolayer graphene. The presence of spin polarized background electrons population, with density corresponding to highly degenerate conditions is assumed. Formulas of electron-electron scattering rates, which properly account for electrons presence in two energetically degenerate, inequivalent valleys in this material are presented. The electron relaxation process can be divided into two phases: thermalization and cooling, which can be clearly distinguished when examining the standard deviation of electron energy distribution. The influence of the exchange effect in interactions between electrons with parallel spins is shown to be important only in transient conditions, especially during the thermalization phase.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

Directory of Open Access Journals (Sweden)

Ratih S. I. Putri

2016-11-01

Full Text Available The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t, the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach Cmax (tmax, and the plasma concentration half-life (t1/2. To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%, 95.53% (89.75%–101.68%, and 92.11% (84.35%–100.58% for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.

Science.gov (United States)

Putri, Ratih S I; Setiawati, Effi; Aziswan, Syifa A; Ong, Fenny; Tjandrawinata, Raymond R; Susanto, Liana W

2016-11-18

The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC 0-t ), the area under the plasma concentration curve extrapolated to infinite time (AUC 0-∞ ), the maximum plasma concentration (C max ), the time to reach C max (t max ), and the plasma concentration half-life (t 1/2 ). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and C max parameters, while t max and t 1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired t -test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC 0-t , AUC 0-∞ , and C max , respectively. There were no statistically significant differences for t max and t 1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

bioequivalence study on two 10% enrofloxacin oral formulations

African Journals Online (AJOL)

AONDOVER

sampled before and after drug administration for 24 hours. Plasma enrofloxacin ... Pharmacokinetic studies have indicated ... variation of the inhibitory effect of antibiotics on .... These factors determine .... dependent, the in vivo performance of.

[Availability of generic drugs in the public sector and prices in the private sector in different regions of Brazil].

Science.gov (United States)

Miranda, Elaine Silva; Pinto, Cláudia Du Bocage Santos; dos Reis, André Luis de Almeida; Emmerick, Isabel Cristina Martins; Campos, Mônica Rodrigues; Luiza, Vera Lucia; Osorio-de-Castro, Claudia Garcia Serpa

2009-10-01

A study to identify availability and prices of medicines, according to type of provider, was conducted in the five regions of Brazil. A list of medicines to treat prevalent diseases was investigated, using the medicines price methodology developed by the World Health Organization and Health Action International, adapted for Brazil. In the public sector, bioequivalent (vis-à-vis reference brand) generics are less available than multisource products. For most medicines (71.4%), the availability of bioequivalent generics was less than 10%. In the private sector, the average number of different bioequivalent generic versions in the outlets was far smaller than the number of versions on the market. There was a positive correlation between the number of generics on the market, or those found at outlets, and the price variation in bioequivalent generic products, in relation to the maximum consumer price. It is estimated that price competition is occurring among bioequivalent generic drugs and between them and multisource products for the same substance, but not with reference brands.

Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib

Directory of Open Access Journals (Sweden)

Tjandrawinata RR

2018-04-01

Full Text Available Raymond R Tjandrawinata,1 Arini Setiawati,2 Dwi Nofiarny,1 Liana W Susanto,1 Effi Setiawati3 1Dexa Laboratories of Biomolecular Sciences Unit, Dexa Medica Group, Cikarang, West Java, Indonesia; 2Department of Pharmacology and Therapeutics, Medical Faculty, University of Indonesia, Jakarta, Indonesia; 3Bioavailability and Bioequivalence Laboratory Unit, PT Equilab International, Jakarta, Indonesia Purpose: The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg.Methods: This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4 using a high-pressure liquid chromatography–ultraviolet detector (HPLC-UV system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration–time curve from time zero to the time of last observed concentration (AUC0-t, the area under plasma concentration–time curve from time zero to infinity (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach the maximum plasma concentration (tmax, and the terminal half-life (t½.Results: After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD values for the AUC0-72h and Cmax of the test drug were 45913.42 (13142.19 ng·h/mL and 3155.93 (752.81 ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85 ng⋅h/mL and 2915.13 (772.81 ng/mL, respectively. The geometric mean ratios (90% CIs of the test

Pharmacology of biosimilar candidate drugs in rheumatology: a literature review.

Science.gov (United States)

Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E

2014-01-01

To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.

Study of electron transmission through thin metallic films by the electron moessbauer spectroscopy

International Nuclear Information System (INIS)

Babikova, Yu.F.; Vakar, O.M.; Gruzin, O.M.; Petrikin, Yu.V.

1983-01-01

Results of the experimental study of the transmission of conversion electrons through aluminium, iron, tin and gold films are presented. Absorption of resonance electrons of the Moessbauer nuclide 57 Fe, formed during target irradiation with γ-quanta of 57 Co source in chromium matrix has been studied. It is asserted that absorption of conversion electrons in films of different elements is similar; at that, like in the case of β-particles, the law of absorption of resonance electrons, emitted from the flat layer, is exponential For conversion electrons of the Moessbauer nuclide 57 Fe the absorption coefficient is (0.025+-0.002) cm 2 /μg, which in the case of iron absorbing film corresponds to (20.0+-1.0)x10 4 cm -1

Bioequivalence evaluation of new microparticulate capsule and ...

African Journals Online (AJOL)

data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann's two one-sided t-test ... The reasons for low compliance of NSAIDs ... 7.32 cm (range, 168.2 - 190.93 cm); and BMI, ... blood pressure and body temperature) were ... Figure 1: Scanning electron microscopy image of AF-7 microparticles.

Generic drugs: myths, facts, and limitations

Directory of Open Access Journals (Sweden)

Antonio Marzo

2012-10-01

Full Text Available Bioequivalence (BE has always been an important pharmaceutical area, particularly (but not solely in Mediterranean region, where the use of generic drugs is a relatively recent development. The lack of new therapeutic molecules has concentrated primary research in the hands of a few large pharmaceutical companies. For smaller companies, this has created opportunities for the development of new formulations of existing drugs (orodispersible tablets that dissolve in the mouth, extended-release tablets, transdermal delivery systems, generic drugs. These applications take advantage of the Abridged New Drug Application (ANDA procedure, which exempts them from a series of expensive investigations and limits the requirement for clinical testing to bioequivalence trials. Since 1991, bioequivalence trials have been regulated by US Food and Drug Administration (FDA and European Medicines Agency (EMA guidelines that provide precise indications on the most specific procedures to be adopted. In spite of these guidelines, however, some aspects of the process have not been fully defined, the most important of which regards the management of endogenous substances. Additional problems are how to manage bioequivalence protocols with drugs that have long half-lives and those whose clearance is characterized by high intrinsic variability. The view that bioequivalence data would be more reliable if they were based on studies in target populations is a myth to be discredited. The present paper reviews issues relative to pharmacokinetics (PK, bioavailability (BA, and bioequivalence, also from an historical viewpoint, and includes a stimulating “questions and answers” section on some key aspects of the bioequivalence of generic drugs.

Establishment of in vitro-in vivo equivalence of highly variable drugs - a generic product development perspective.

Science.gov (United States)

Pathak, Shriram M; Aggarwal, Deepika; Venkateswarlu, V

2014-06-01

In vivo equivalence of highly variable drugs (HVD) has always been a subject of great concern, in terms of both safety and efficacy, for regulatory agencies. Successful demonstration of their bioequivalence thus presents the most crucial component of a generic application, significantly contributing toward the cost and time of development. For poorly soluble drugs, such as telmisartan, dissolution represents the rate-limiting step in the gastric region and in many cases may not be complete, thereby contributing to low and highly variable bioavailability. Consequently, simulation of gastrointestinal conditions is essential to adequately predict the in vivo behavior of drug formulations. In this study, we evaluated usefulness of physiologically relevant dissolution method over commonly used acidic media to forecast comparable in vivo performance of telmisartan formulation to that of reference samples. In the present study, telmisartan was classified as a HVD and a partial replicate design with repeating the reference product and scaling the bioequivalence for the reference variability has been presented. The design has effectively decreased sample size, without increasing patient risk. Results from this project suggest that scaled average bioequivalence (SABE) provides a good approach for evaluating the bioequivalence of HVD, meeting the need for international guidelines for bioequivalence.

Quantification of strontium in human serum by ICP-MS using alternate analyte-free matrix and its application to a pilot bioequivalence study of two strontium ranelate oral formulations in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Wang, Xiaolin; Liu, Man; Zhang, Lina; Deng, Ming; Liu, Huichen

2015-01-01

A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00-500ng/mL, corresponding to a concentration range of 0.0300-15.0μg/mL in 50μL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate. Copyright © 2014 Elsevier GmbH. All rights reserved.

Transmission electron microscope studies of extraterrestrial materials

Science.gov (United States)

Keller, Lindsay P.

1995-01-01

Transmission Electron Microscopy, X-Ray spectrometry and electron-energy-loss spectroscopy are used to analyse carbon in interplanetary dust particles. Optical micrographs are shown depicting cross sections of the dust particles embedded in sulphur. Selected-area electron diffraction patterns are shown. Transmission Electron Microscope specimens of lunar soil were prepared using two methods: ion-milling and ultramicrotomy. A combination of high resolution TEM imaging and electron diffraction is used to characterize the opaque assemblages. The opaque assemblages analyzed in this study are dominated by ilmenite with lesser rutile and spinel exsolutions, and traces of Fe metal.

Studies of electron cyclotron emission on text

International Nuclear Information System (INIS)

Gandy, R.F.

1990-07-01

The Auburn University electron cyclotron emission (ECE) system has made many significant contributions to the TEXT experimental program during the past five years. Contributions include electron temperature information used in the following areas of study: electron cyclotron heating (ECH), pellet injection, and impurity/energy transport. Details of the role which the Auburn ECE system has played will now be discussed

Dissociative electron attachment studies on acetone

International Nuclear Information System (INIS)

Prabhudesai, Vaibhav S.; Tadsare, Vishvesh; Ghosh, Sanat; Gope, Krishnendu; Davis, Daly; Krishnakumar, E.

2014-01-01

Dissociative electron attachment (DEA) to acetone is studied in terms of the absolute cross section for various fragment channels in the electron energy range of 0–20 eV. H − is found to be the most dominant fragment followed by O − and OH − with only one resonance peak between 8 and 9 eV. The DEA dynamics is studied by measuring the angular distribution and kinetic energy distribution of fragment anions using Velocity Slice Imaging technique. The kinetic energy and angular distribution of H − and O − fragments suggest a many body break-up for the lone resonance observed. The ab initio calculations show that electron is captured in the multi-centered anti-bonding molecular orbital which would lead to a many body break-up of the resonance

Some recent studies of electron swarms in gases

International Nuclear Information System (INIS)

Tagashira, H.

1992-01-01

Some recent studies of electron swarms in gases under the action of an electric field are introduced. The studies include a new type of continuity equation for electrons having a form in which the partial derivative of the electron density with respect to position and to time are interchanged, a method to deduce the time-of-flight and arrival-time-spectrum swarm parameters based on a Fourier-transformed Boltzmann equation, an examination of the correspondence between experimental and theoretical electron drift velocities, and an automatic technique to deduce the electron-gas molecule collision cross section from electron drift velocity data. A method for the deduction of electron collision cross sections with gas molecules having vibrational excitation cross sections greater than the elastic momentum transfer cross section by using a gas mixture technique, an integral type of method for solution of the Boltzmann equation with salient numerical stability, a quantitative analysis of the effect of Penning ionisation, and the behaviour of electron swarms under radio frequency electric fields, are also briefly discussed. 28 refs., 3 figs

Modified Monte Carlo method for study of electron transport in degenerate electron gas in the presence of electron-electron interactions, application to graphene

Science.gov (United States)

Borowik, Piotr; Thobel, Jean-Luc; Adamowicz, Leszek

2017-07-01

Standard computational methods used to take account of the Pauli Exclusion Principle into Monte Carlo (MC) simulations of electron transport in semiconductors may give unphysical results in low field regime, where obtained electron distribution function takes values exceeding unity. Modified algorithms were already proposed and allow to correctly account for electron scattering on phonons or impurities. Present paper extends this approach and proposes improved simulation scheme allowing including Pauli exclusion principle for electron-electron (e-e) scattering into MC simulations. Simulations with significantly reduced computational cost recreate correct values of the electron distribution function. Proposed algorithm is applied to study transport properties of degenerate electrons in graphene with e-e interactions. This required adapting the treatment of e-e scattering in the case of linear band dispersion relation. Hence, this part of the simulation algorithm is described in details.

Runaway-electron-materials interaction studies

International Nuclear Information System (INIS)

Bolt, H.; Miyahara, A.

1990-03-01

During the operation of magnetic fusion devices it has been frequently observed that runaway electrons can cause severe damage to plasma facing components. The energy of the runaway electrons could possibly reach several 100 MeV in a next generation device with an energy content in the plasma in the order of 100 MJ. In this study effects of high energy electron - materials interaction were determined by laboratory experiments using particle beam facilities, i.e. the Electron Linear Accelerator of the Institute of Scientific and Industrial Research of Osaka University and the 10 MW Neutral Beam Injection Test Stand of the National Institute for Fusion Science. The experiments and further analyses lead to a first assessment of the damage thresholds of plasma facing materials and components under runaway electron impact. It was found that metals (stainless steel, molybdenum, tungsten) showed grain growth, crack formation and/or melting already below the threshold for crack initiation on graphite (14-33 MJ/m 2 ). Strong erosion of carbon materials would occur above 100 MJ/m 2 . Damage to metal coolant channels can occur already below an energy deposition of 100 MJ/m 2 . The energy deposited in the metal coolant channels depends on the thickness of the plasma facing carbon material D, with the shielding efficiency S of carbon approximately as S∼D 1.15 . (author) 304 refs. 12 tabs. 59 figs

Electron scattering studies by means of various nuclear models

International Nuclear Information System (INIS)

Essaniyazov, Sh.; Juraev, Sh.; Ismatov, E.I.

2006-01-01

Full text: Let us consider a general case of various interaction processes of electrons with nuclei. The study of the scattering o electrons of nuclei is the source of information on the structure of nuclei. At collision of fast electrons with nuclei, both elastic and inelastic scattering can be observed. Elastic scattering gives information on the sizes of nuclei, whereas the electrons inelastic scattering processes give important information on the dynamical properties of nuclei. In the first case, the characteristics of excited states, energy levels, their widths and others, and in the second case, momentum distribution of nucleons and other particles in nuclei are studied. Let us denote the momentum and the energy of the incident electron before and after the scattering as k and ε, and k' and ε', respectively. The angle between the vectors k and k' is denoted as θ. The scattering process is characterized by three parameters: k, k' and θ. However, it is convenient to introduce three other parameters instead of the indicated above. They are: energy ω ε - ε' and momentum q = k - k', transferred by electron at scattering, and the scattering angle θ. It is worth of mentioning the two reasons why the study of electron scattering is very effective tool to study the nuclear structure. First of all, the character of electron interaction with nucleus is a well-known electromagnetic interaction of electron with current and charge in nucleus. Secondly, this interaction is relatively weak (e 2 /ℎc) 2 = ω 2 is possible (since the photon mass is zero). In case of electrons, at fixed energy transfer ω various momentum transfer are possible. Therefore, at electron scattering study one can establish the dependence of the matrix elements of q, which are the Fourier-representations of the charge and current densities. Thus, it is possible to determine directly the spatial distribution of charge and current in nucleus. The inelastic scattering is accompanied by

Dissociative electron attachment studies on acetone

Energy Technology Data Exchange (ETDEWEB)

Prabhudesai, Vaibhav S., E-mail: vaibhav@tifr.res.in; Tadsare, Vishvesh; Ghosh, Sanat; Gope, Krishnendu; Davis, Daly; Krishnakumar, E. [Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005 (India)

2014-10-28

Dissociative electron attachment (DEA) to acetone is studied in terms of the absolute cross section for various fragment channels in the electron energy range of 0–20 eV. H{sup −} is found to be the most dominant fragment followed by O{sup −} and OH{sup −} with only one resonance peak between 8 and 9 eV. The DEA dynamics is studied by measuring the angular distribution and kinetic energy distribution of fragment anions using Velocity Slice Imaging technique. The kinetic energy and angular distribution of H{sup −} and O{sup −} fragments suggest a many body break-up for the lone resonance observed. The ab initio calculations show that electron is captured in the multi-centered anti-bonding molecular orbital which would lead to a many body break-up of the resonance.

A coincidence study between photo- and Auger electrons

International Nuclear Information System (INIS)

Ricz, S.; Koever, A.; Varga, D.; Molnar, J.; Aksela, S.; Jurvansuu, M.

2000-01-01

Complete text of publication follows. The investigation of double differential cross sections of photon induced Auger electrons provides very sensitive method for studying the rearrangement process, especially when the angular correlation between photo- and Auger electrons is also studied. Such type of measurements could reveal a new aspect in studying the electron-electron, hole-electron and photoelectron - Auger electron interactions. It enables one to separate the overlapping Auger lines belonging to different initial holes. The traditional coincidence measurement is very time consuming and causes serious calibration problems. In order to overcome these experimental difficulties a new electron-spectrometer (ESA-22) was developed in ATOMKI, Debrecen in cooperation with the Electron spectroscopy group of University of Oulu, Finland. The analyzer consists of a spherical and a cylindrical part. It is very similar to the ESA-21 analyzer. The main differences is that the focal ring can be set different diameters thus either a series of channel detectors can be used to detect the electrons at different angles or a position sensitive channel plate can be applied for simultaneous angular recording of electrons. Furthermore the outer sphere and cylinder are cut into two parts so the spectrometer is capable to analyze two independent angularly resolved electron spectra (in the 0 deg - 180 deg region) at different energy regions, simultaneously. A special electronic control and data handling electronics and software was worked out to control the analyzer. The first results were presented in. In the last year the ESA-22 electron-spectrometer was transported to the I411 beam line of MAX-II synchrotron in Lund, Sweden. The advanced properties of the spectrometer was investigated by measuring coincidences between the photoelectrons originated from the Ar L 3 subshell and the Ar Auger electrons in the 203-207 eV energy region. Fig. 1 shows the single and the coincidence spectra

Development techniques and electron optical studies of high voltage, high current electron guns

International Nuclear Information System (INIS)

Rangarajan, L.M.; Mahadevan, S.; Ramamurthi, S.S.

1992-01-01

The progress of the electron gun design, limiting to axially symmetric geometries is discussed here with a view to utilise such guns for electron accelerators. The mechanical design features leading to the physical configuration of the gun with stringent tolerances are outlined. Vacuum processing is done at pressures of 1.3x10 -5 Pa. The gun employs W-filament emitter or a cathode pellet with bombarder service. A water cooled compact faraday cup is used to measure the electron current. Electron gun geometries have been studied using the computer programme. The preveance of the gun is 0.7x10 -7 A/Vsup(1.5) at 80 kV. Developmental techniques of such pulsed electron guns are described. (author). 7 refs., 5 figs

A kinetic study of solar wind electrons

International Nuclear Information System (INIS)

Lie-Svendsen, Oeystein; Leer, Egil

1996-01-01

The evolution of the distribution function for a test population of electrons in an isothermal electron-proton corona has been studied using a Fokker-Planck description. The aim is to investigate whether a suprathermal tail forms due to the energy dependence of the Coulomb cross section. We find that a Maxwellian test population, injected into this background close to the coronal base with a temperature equal to that of the background electrons, maintains its shape throughout the transition from collision-dominated to collisionless flow. No significant suprathermal tail in the electron distribution function is seen in the outer corona

Electron emission relevant to inner-shell photoionization of condensed water studied by multi-electron coincidence spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Hikosaka, Y., E-mail: hikosaka@las.u-toyama.ac.jp [Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Mashiko, R.; Konosu, Y.; Soejima, K. [Department of Environmental Science, Niigata University, Niigata 950-2181 (Japan); Shigemasa, E. [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); SOKENDAI, Okazaki 444-8585 (Japan)

2016-11-15

Highlights: • Multi-electron coincidence spectroscopy is applied to the study of electron emissions from condensed H2O molecules. • Coincidence Auger spectra are obtained for different photoelectron energies. • The energy distribution of the slow electrons ejected in the Auger decay is deduced from three-fold coincidences. - Abstract: Multi-electron coincidence spectroscopy using a magnetic-bottle electron spectrometer has been applied to the study of the Auger decay following O1s photoionization of condensed H{sub 2}O molecules. Coincidence Auger spectra are obtained for three different photoelectron energy ranges. In addition, the energy distribution of the slow electrons ejected in the Auger decay of the O1s core hole is deduced from three-fold coincidences.

A phase 1 study to evaluate effect of food on veliparib pharmacokinetics and relative bioavailability in subjects with solid tumors.

Science.gov (United States)

Mostafa, Nael M; Chiu, Yi-Lin; Rosen, Lee S; Bessudo, Alberto; Kovacs, Xenia; Giranda, Vincent L

2014-09-01

A phase 1 study was conducted to evaluate the bioavailability and food effect of a new veliparib formulation in subjects with solid tumors. Subjects (planned: Stage I, N = 20; Stage II, N = 16) received four regimens of a single oral dose of veliparib utilizing a group-sequential design. Subjects were administered single doses of 40 mg veliparib supplied as four 10 mg current formulation, four 10 mg new formulation and one 40 mg new formulation under fasting conditions and under non-fasting conditions. Serial blood samples were collected for the determination of veliparib pharmacokinetics. At the end of Stage I, the relative bioavailability between each pair of regimens was assessed by a two one-sided tests procedure from the analyses of the natural logarithms of C(max) and AUC. A 92.7 % confidence interval within the 0.80-1.25 range between each regimen pair determined bioequivalence. Four 10 mg current formulation capsules, four 10 mg new formulation and one 40 mg new formulation were bioequivalent with respect to C(max) and AUC under fasting conditions. The administration of a high-fat meal did not have a significant effect on AUC and only caused a slight decrease in veliparib C(max) (17 %) and a delay of approximately 1 h in T(max). The 40 mg new capsule was bioequivalent to currently used formulation. Food had no effect on the extent of veliparib absorption and only a small (17 %) decrease in peak exposure of veliparib.

Digital technique for the study of narrow structure in electron-atom and electron-molecule scattering

International Nuclear Information System (INIS)

Paske, W.C.; Shadfar, S.; Lorentz, S.R.; Steph, N.C.; Golden, D.E.

1981-01-01

A digital technique has been developed which allows the study of narrow structure in total electron-atom and electron-molecule scattering cross sections without requiring a highly monoenergetic electron beam, modulation of the electron gun, or phase sensitive detection. The electron current transmitted through a gas cell is digitized as the electron energy is stepped by ΔE through the energy range of interest. A transmitted electron difference signal is then obtained using a computer. As examples of this technique, the difference spectra are presented for He near 19.35 eV and for N 2 for the energy range from 10.3 to 15.0 eV. In the present case an instrumental resolution of 30 meV FWHM has been obtained

Transmission Electron Microscopy Studies of Electron-Selective Titanium Oxide Contacts in Silicon Solar Cells

KAUST Repository

Ali, Haider; Yang, Xinbo; Weber, Klaus; Schoenfeld, Winston V.; Davis, Kristopher O.

2017-01-01

In this study, the cross-section of electron-selective titanium oxide (TiO2) contacts for n-type crystalline silicon solar cells were investigated by transmission electron microscopy. It was revealed that the excellent cell efficiency of 21

Studying the electronic customer relationship management and its ...

African Journals Online (AJOL)

Studying the electronic customer relationship management and its effect on bank quality outcomes. ... Journal of Fundamental and Applied Sciences ... Keywords: Electronic Banking, Service Quality, Customer Satisfaction, Management of

Bioequivalence of a biosimilar enoxaparin sodium to Clexane® after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers

Directory of Open Access Journals (Sweden)

Martínez González J

2018-03-01

Full Text Available Javier Martínez González, Mayte Monreal, Ignacio Ayani Almagia, Jordi Llaudó Garín, Lourdes Ochoa Díaz de Monasterioguren, Ibón Gutierro Adúriz R&D Department, Laboratorios Farmacéuticos Rovi S.A., Madrid, Spain Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. Patients and methods: A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain and Clexane® (enoxaparin 100 mg manufactured by Sanofi, reference separated by a 1-week washout period. The primary PK/PD variables were maximum activity (Amax and area under the effect curve from time 0 to the last measured activity (T (AUEC0–T and AUEC from time 0 to infinity (AUEC0–inf of anti-FXa activity, and Amax and AUEC0–T of anti-FIIa activity. Secondary variables were Amax and AUEC0–T, AUEC0–inf of tissue factor pathway inhibitor, and the ratio of AUEC0–T anti-FXa to anti-FIIa activity. Biosimilarity would be shown when the 95% CI of the ratio of geometric least squares means (95% CI RGLSMs of primary PK/PD parameters fell within the standard range of bioequivalence, ie, 80%–125%.Results: The study sample consisted of 46 volunteers (33 males aged 18–44 years and with body mass index ranging from 19.0 to 31.1 kg/m2. Three subjects did not complete the study. The curves of anti-FXa, anti-FIIa and tissue factor pathway inhibitor activities corresponding to administration of the test and reference products were comparable. The 95% CI RGLSMs of Amax, AUEC0–T and AUEC0–inf for anti-FXa activity were 94.6%–105.9%, 99.8%–108.0% and 100.0%–108.6% respectively; Amax and AUEC0–T for anti-FIIa activity were 94.7%–112.6% and

NATO Advanced Study Institute on Electron Crystallography

CERN Document Server

Weirich, Thomas E; Zou, Xiaodong

2006-01-01

During the last decade we have been witness to several exciting achievements in electron crystallography. This includes structural and charge density studies on organic molecules complicated inorganic and metallic materials in the amorphous, nano-, meso- and quasi-crystalline state and also development of new software, tailor-made for the special needs of electron crystallography. Moreover, these developments have been accompanied by a now available new generation of computer controlled electron microscopes equipped with high-coherent field-emission sources, cryo-specimen holders, ultra-fast CCD cameras, imaging plates, energy filters and even correctors for electron optical distortions. Thus, a fast and semi-automatic data acquisition from small sample areas, similar to what we today know from imaging plates diffraction systems in X-ray crystallography, can be envisioned for the very near future. This progress clearly shows that the contribution of electron crystallography is quite unique, as it enables to r...

Electron cloud buildup studies for the LHC

CERN Document Server

AUTHOR|(CDS)2160803; Boine-Frankenheim, Oliver

Electron clouds can develop in accelerators operating with positively charged particles. The con- sequences of e-cloud related effects are very important for the operation of the Large Hadron Collider (LHC) at CERN, and for the design of future accelerators including the LHC luminosity upgrade (HL-LHC). High electron densities are generated by an interaction between the beam and the confining chamber. Primary electrons, that can be generated through various mecha- nisms, are accelerated by the beam and impinge on the chamber walls, thereby extracting more electrons from the material. Furthermore they also deposit their kinetic energy in the process, which has to be compensated by the cooling system. Especially in cryogenic environments, as it is the case for a large part of the LHC, high heat loads can pose a serious problem. In order to improve the understanding of the electron cloud, simulation studies are performed with the code PyECLOUD, developed at CERN. The work of the first half of the project is desc...

Electronics Industry Study Report

National Research Council Canada - National Science Library

Belt, David; Fellows, John R; Kameru, Philip; Nazaroff, Boris-Frank A; Pauroso, Anthony; Schulz, Frederick; Ballew, Bob; Bond, Thomas; Demers, Stephy; Kirkpatrick, Steve

2005-01-01

This paper provides a national strategy for the US electronics industry. Electronics is one of the largest industries in the US and plays a critical role in almost every aspect of national security...

Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

Science.gov (United States)

Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

2010-10-01

The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were fasting, healthy Chinese male volunteers. Both formulations appeared to be well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

Fast electron transport study for inertial confinement fusion

International Nuclear Information System (INIS)

Touati, Michael

2015-01-01

A new hybrid reduced model for relativistic electron beam transport in solids and dense plasmas is presented. It is based on the two first angular moments of the relativistic kinetic equation completed with the Minerbo maximum angular entropy closure. It takes into account collective effects with the self-generated electromagnetic fields as well as collisional effects with the slowing down of the electrons in collisions with plasmons, bound and free electrons and their angular scattering on both ions and electrons. This model allows for fast computations of relativistic electron beam transport while describing the kinetic distribution function evolution. Despite the loss of information concerning the angular distribution of the electron beam, the model reproduces analytical estimates in the academic case of a collimated and monoenergetic electron beam propagating through a warm and dense Hydrogen plasma and hybrid PIC simulation results in a realistic laser-generated electron beam transport in a solid target. The model is applied to the study of the emission of Kα photons in laser-solid experiments and to the generation of shock waves. (author) [fr

Electron tunneling in lithium-ammonia solutions probed by frequency-dependent electron spin relaxation studies.

Science.gov (United States)

Maeda, Kiminori; Lodge, Matthew T J; Harmer, Jeffrey; Freed, Jack H; Edwards, Peter P

2012-06-06

Electron transfer or quantum tunneling dynamics for excess or solvated electrons in dilute lithium-ammonia solutions have been studied by pulse electron paramagnetic resonance (EPR) spectroscopy at both X- (9.7 GHz) and W-band (94 GHz) frequencies. The electron spin-lattice (T(1)) and spin-spin (T(2)) relaxation data indicate an extremely fast transfer or quantum tunneling rate of the solvated electron in these solutions which serves to modulate the hyperfine (Fermi-contact) interaction with nitrogen nuclei in the solvation shells of ammonia molecules surrounding the localized, solvated electron. The donor and acceptor states of the solvated electron in these solutions are the initial and final electron solvation sites found before, and after, the transfer or tunneling process. To interpret and model our electron spin relaxation data from the two observation EPR frequencies requires a consideration of a multiexponential correlation function. The electron transfer or tunneling process that we monitor through the correlation time of the nitrogen Fermi-contact interaction has a time scale of (1-10) × 10(-12) s over a temperature range 230-290 K in our most dilute solution of lithium in ammonia. Two types of electron-solvent interaction mechanisms are proposed to account for our experimental findings. The dominant electron spin relaxation mechanism results from an electron tunneling process characterized by a variable donor-acceptor distance or range (consistent with such a rapidly fluctuating liquid structure) in which the solvent shell that ultimately accepts the transferring electron is formed from random, thermal fluctuations of the liquid structure in, and around, a natural hole or Bjerrum-like defect vacancy in the liquid. Following transfer and capture of the tunneling electron, further solvent-cage relaxation with a time scale of ∼10(-13) s results in a minor contribution to the electron spin relaxation times. This investigation illustrates the great

Electron Tunneling in Lithium Ammonia Solutions Probed by Frequency-Dependent Electron-Spin Relaxation Studies

Science.gov (United States)

Maeda, Kiminori; Lodge, Matthew T.J.; Harmer, Jeffrey; Freed, Jack H.; Edwards, Peter P.

2012-01-01

Electron transfer or quantum tunneling dynamics for excess or solvated electrons in dilute lithium-ammonia solutions have been studied by pulse electron paramagnetic resonance (EPR) spectroscopy at both X- (9.7 GHz) and W-band (94 GHz) frequencies. The electron spin-lattice (T1) and spin-spin (T2) relaxation data indicate an extremely fast transfer or quantum tunneling rate of the solvated electron in these solutions which serves to modulate the hyperfine (Fermi-contact) interaction with nitrogen nuclei in the solvation shells of ammonia molecules surrounding the localized, solvated electron. The donor and acceptor states of the solvated electron in these solutions are the initial and final electron solvation sites found before, and after, the transfer or tunneling process. To interpret and model our electron spin relaxation data from the two observation EPR frequencies requires a consideration of a multi-exponential correlation function. The electron transfer or tunneling process that we monitor through the correlation time of the nitrogen Fermi-contact interaction has a time scale of (1–10)×10−12 s over a temperature range 230–290K in our most dilute solution of lithium in ammonia. Two types of electron-solvent interaction mechanisms are proposed to account for our experimental findings. The dominant electron spin relaxation mechanism results from an electron tunneling process characterized by a variable donor-acceptor distance or range (consistent with such a rapidly fluctuating liquid structure) in which the solvent shell that ultimately accepts the transferring electron is formed from random, thermal fluctuations of the liquid structure in, and around, a natural hole or Bjerrum-like defect vacancy in the liquid. Following transfer and capture of the tunneling electron, further solvent-cage relaxation with a timescale of ca. 10−13 s results in a minor contribution to the electron spin relaxation times. This investigation illustrates the great potential

A study on the secondary electrons in a clinical electron beam

International Nuclear Information System (INIS)

Krithivas, G.; Rao, S.N.

1989-01-01

The central axis dose of a 12 MeV clinical electron beam is investigated in terms of an axial component due to primary electrons in the central ray and a lateral component due to secondary electrons originating from multiple scattering of electrons in the off-axis rays. To this effect secondary electron fluence measurements in a polystyrene medium irradiated with a collimated beam are made with a sensitive diode detector. This leads to a construction of secondary electron depth-dose profiles for beam sizes of diameters ranging from 1.7 to 17.4 cm. The results indicate that the lateral electrons account for 25% of the dose in the therapeutic region. For these electrons, the depth of dose maximum is correlated with diffusion depth and maximum lateral excursion in the medium. Dose component due to backscatter electrons at depths is also investigated using a thin-window parallel-plate ion chamber. The role of lateral and backscatter electrons in characterising central axis per cent depth-dose is discussed. (author)

Os estudos de bioequivalência: Relevância para a medicina veterinária

Directory of Open Access Journals (Sweden)

João Palermo-Neto

2008-12-01

Full Text Available Bioequivalence (BE studies are scientific methods that allow comparison of different medicinal products containing the same active substance, or different batches of the same medicinal products or, in a broad sense, different routes of administration of the same product.Actually, legislation on generic drugs and bioequivalence only exist in Brazil for drugs intended for human purposes. In the field of Veterinary Medicine, BE is being used in many countries as part of the necessary requirements for registration of animal health products, i.e., to provide efficacy and safety animal data and to allow consumers safety; indeed, they also assure the quality of the food derived from treated animals. The present manuscript was designed to review and discuss BE; for that, it was divided into three major parts: 1- understanding bioequivalence: importance of BE studies for animal and human health; 2- type of BE studies included; 3- general consideration on experimental design involved o BE studies

Physical methods for studying minerals and solid materials: X-ray, electron and neutron diffraction; scanning and transmission electron microscopy; X-ray, electron and ion spectrometry

International Nuclear Information System (INIS)

Eberhart, J.-P.

1976-01-01

The following topics are discussed: theoretical aspects of radiation-matter interactions; production and measurement of radiations (X rays, electrons, neutrons); applications of radiation interactions to the study of crystalline materials. The following techniques are presented: X-ray and neutron diffraction, electron microscopy, electron diffraction, X-ray fluorescence analysis, electron probe microanalysis, surface analysis by electron emission spectrometry (ESCA and Auger electrons), scanning electron microscopy, secondary ion emission analysis [fr

In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

Science.gov (United States)

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

2012-01-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

First principles studies of electron tunneling in proteins

Science.gov (United States)

Hayashi, Tomoyuki; Stuchebrukhov, Alexei A.

2014-01-01

A first principles study of electronic tunneling along the chain of seven Fe/S clusters in respiratory complex I, a key enzyme in the respiratory electron transport chain, is described. The broken-symmetry states of the Fe/S metal clusters calculated at both DFT and semi-empirical ZINDO levels were utilized to examine both the extremely weak electronic couplings between Fe/S clusters and the tunneling pathways, which provide a detailed atomistic-level description of the charge transfer process in the protein. One-electron tunneling approximation was found to hold within a reasonable accuracy, with only a moderate induced polarization of the core electrons. The method is demonstrated to be able to calculate accurately the coupling matrix elements as small as 10−4 cm−1. A distinct signature of the wave properties of electrons is observed as quantum interferences of multiple tunneling pathways. PMID:25383312

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

Science.gov (United States)

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
.

Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

Science.gov (United States)

Agrawal, Shrutidevi; Singh, Inderjit; Kaur, Kanwal Jit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2004-05-19

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

High Pressure X-ray Absorption Studies on Correlated-Electron Systems

International Nuclear Information System (INIS)

Cornelius, Andrew L.

2016-01-01

This project used high pressure to alter the electron-electron and electron-lattice interactions in rare earth and actinide compounds. Knowledge of these properties is the starting points for a first-principles understanding of electronic and electronically related macroscopic properties. The research focused on a systematic study of x-ray absorption measurements on rare earth and actinide compounds.

A coordinated two-satellite study of energetic electron precipitation events

International Nuclear Information System (INIS)

Imhof, W.L.; Nakano, G.H.; Gaines, E.E.; Reagan, J.B.

1975-01-01

A new technique for studying the spatial/temporal variations of energetic electron precipitation events is investigated. Data are presented in which precipitating electrons were measured simultaneously on two coordinated polar-orbiting satellites and the bremsstrahlung produced by the electrons precipitating into the atmosphere was observed from one of the satellites. Two electron spectrometers measuring the intensities and energy spectra of electrons of >130 keV were located on the oriented satellite 1971-089A (altitude, approx. =800 km), whereas a single similar spectrometer measuring electrons of >160 keV was located on the spinning low-altitude (approx.750 km) satellite 1972-076B. The X rays of >50 keV were measured with a 50-cm 3 germanium spectrometer placed on the 1972-076B satellite. With the coordinated data a study is made of events in which large fluctuations were observed in the precipitating energetic electron intensities. In the examples presented the satellite X ray data alone demonstrate that the spatially integrated electron influx was constant in time, and when the X ray data are combined with the direct electron measurements from the two satellites, the resulting data suggest that the major features in the flux profiles were primarily spatial in nature. The combination of X ray and electron measurements from two satellites is shown to provide an important method for studying and attempting to resolve spatial and temporal effects

Theoretical study of the interplay of electron-electron interaction and disorder

International Nuclear Information System (INIS)

Brezini, A.; Behilil, S.

1988-10-01

A disordered Hubbard model with diagonal disorder is used to investigate the electron localization effects associated with both disorder and electron-electron interaction. Extensive results are reported on the ground state properties and compared to other theories. Two regimes have been found: when the electron-electron interaction u is greater than the disorder parameter w and when u < w. (author). 18 refs, 4 figs

Laser-induced electron--ion recombination used to study enhanced spontaneous recombination during electron cooling

International Nuclear Information System (INIS)

Schramm, U.; Wolf, A.; Schuess ler, T.; Habs, D.; Schwalm, D.; Uwira, O.; Linkemann, J.; Mueller, A.

1997-01-01

Spontaneous recombination of highly charged ions with free electrons in merged velocity matched electron and ion beams has been observed in earlier experiments to occur at rates significantly higher than predicted by theoretical estimates. To study this enhanced spontaneous recombination, laser induced recombination spectra were measured both in velocity matched beams and in beams with well defined relative velocities, corresponding to relative electron-ion detuning energies ranging from 1 meV up to 6.5 meV where the spontaneous recombination enhancement was found to be strongly reduced. Based on a comparison with simplified calculations, the development of the recombination spectra for decreasing detuning energies indicates additional contributions at matched velocities which could be related to the energy distribution of electrons causing the spontaneous recombination rate enhancement

Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

Directory of Open Access Journals (Sweden)

Spencer C. Greene, MD, FACEP, FACMT

2016-01-01

Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

The theoretical study of the optical klystron free electron laser

International Nuclear Information System (INIS)

Yang Zhenhua

2001-01-01

The work of the theoretical study and numerical simulation of optical klystron free electron laser is supported by National 863 Research Development Program and National Science Foundation of China. The object of studying UV band free electron laser (FEL) is to understand the physical law of optical klystron FEL and to gain experience for design. A three-dimensional code OPFEL are made and it is approved that the code is correct completely. The magnetic field of the optical klystron, the energy modulation of the electron beam, the density modulation of the electron beam, spontaneous emission of the electron beam in optical klystron, the harmonic super-radiation of the electron beam, and the effects of the undulator magnetic field error on modulation of the electron beam energy are simulated. These results are useful for the future experiments

Electron microscopy methods in studies of cultural heritage sites

Science.gov (United States)

Vasiliev, A. L.; Kovalchuk, M. V.; Yatsishina, E. B.

2016-11-01

The history of the development and application of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray microanalysis (EDXMA) in studies of cultural heritage sites is considered. In fact, investigations based on these methods began when electron microscopes became a commercial product. Currently, these methods, being developed and improved, help solve many historical enigmas. To date, electron microscopy combined with microanalysis makes it possible to investigate any object, from parchment and wooden articles to pigments, tools, and objects of art. Studies by these methods have revealed that some articles were made by ancient masters using ancient "nanotechnologies"; hence, their comprehensive analysis calls for the latest achievements in the corresponding instrumental methods and sample preparation techniques.

Study of the hollow cathode plasma electron-gun

International Nuclear Information System (INIS)

Zhang Yonghui; Jiang Jinsheng; Chang Anbi

2003-01-01

For developing a novel high-current, long pulse width electron source, the theoretics and mechanism of the hollow cathode plasma electron-gun are analyzed in detail in this paper, the structure and the physical process of hollow cathode plasma electron-gun are also studied. This gun overcomes the limitations of most high-power microwave tubes, which employ either thermionic cathodes that produce low current-density beams because of the limitation of the space charge, or field-emission cathodes that offer high current density but provide only short pulse width because of plasma closure of the accelerating gap. In the theories studying on hollow cathode plasma electron-gun, the characteristic of the hollow-cathode discharge is introduced, the action during the forming of plasma of the stimulating electrode and the modulating anode are discussed, the movement of electrons and ions and the primary parameters are analyzed, and the formulas of the electric field, beam current density and the stabilization conditions of the beam current are also presented in this paper. The numerical simulation is carried out based on Poisson's equation, and the equations of current continuity and movement. And the optimized result is reported. On this basis, we have designed a hollow-cathode-plasma electron-gun, whose output pulse current is 2 kA, and pulse width is 1 microsecond

Study and realization of an electron linear accelerator. Dynamics of accelerated electrons

International Nuclear Information System (INIS)

Bernard, J.

1966-12-01

The theoretical characteristics of the electron linear accelerator are: 30 MeV for the energy W S and 250 mA for the peak current I c . The main utilization is the intense production of fast neutrons by the reactions (γ,n) and (γ,f) induced in a target of natural uranium by the accelerated electrons. In the first part of the thesis, relative to the study and the realization of the accelerator, a new equation of dispersion is established analytically when the guide is loaded with round-edged irises. The relation is compared with the equation established by CHU and Hansen, WALKINSHAW, KVASIL in the case of a guide loaded with flat-edged irises. The experimental and theoretical curves of dispersion are compared. The accuracy of every relation of dispersion is estimated. The second part of the thesis is relative to the theoretical study of the electrons dynamics in the guide; it allows the derivation of the parameters of the beam: dispersion of phase, energy, dispersion of energy and the relation W S = f (I c ). The results relative to the first experiments are given and compared with the theoretical expectations. (author) [fr

Progress in Fast Ignition Studies with Electrons and Protons

Science.gov (United States)

MacKinnon, A. J.; Akli, K. U.; Bartal, T.; Beg, F. N.; Chawla, S.; Chen, C. D.; Chen, H.; Chen, S.; Chowdhury, E.; Fedosejevs, R.; Freeman, R. R.; Hey, D.; Higginson, D.; Key, M. H.; King, J. A.; Link, A.; Ma, T.; MacPhee, A. G.; Offermann, D.; Ovchinnikov, V.; Pasley, J.; Patel, P. K.; Ping, Y.; Schumacher, D. W.; Stephens, R. B.; Tsui, Y. Y.; Wei, M. S.; Van Woerkom, L. D.

2009-09-01

Isochoric heating of inertially confined fusion plasmas by laser driven MeV electrons or protons is an area of great topical interest in the inertial confinement fusion community, particularly with respect to the fast ignition (FI) concept for initiating burn in a fusion capsule. In order to investigate critical aspects needed for a FI point design, experiments were performed to study 1) laser-to-electrons or protons conversion issues and 2) laser-cone interactions including prepulse effects. A large suite of diagnostics was utilized to study these important parameters. Using cone—wire surrogate targets it is found that pre-pulse levels on medium scale lasers such as Titan at Lawrence Livermore National Laboratory produce long scale length plasmas that strongly effect coupling of the laser to FI relevant electrons inside cones. The cone wall thickness also affects coupling to the wire. Conversion efficiency to protons has also been measured and modeled as a function of target thickness, material. Conclusions from the proton and electron source experiments will be presented. Recent advances in modeling electron transport and innovative target designs for reducing igniter energy and increasing gain curves will also be discussed. In conclusion, a program of study will be presented based on understanding the fundamental physics of the electron or proton source relevant to FI.

Study of distribution of electron density in heteropolymolybdates by method of X-ray electron spectroscopy

International Nuclear Information System (INIS)

Molchanov, V.N.; Kazanskij, L.P.; Torchenkova, E.A.; Spitsyn, V.I.

1978-01-01

X-ray electron spectra of some iso- and heteropolymolybdates relating to different structure types are investigated to study electron structure of complex polyoxyion-heteropolyanions. Binding energies of Modsub(5/2) and 01s-electrons in iso- and heteropolycompounds line are measured and their interdependence is detected. The effective charge of oxygen and molybdenum atoms in heteropolymolybdates increases with decreasing a number of external sphere cations per an oxygen atom and a number of Mo=0 multiple bonds

Simulation studies on stability of hot electron plasma

International Nuclear Information System (INIS)

Ohsawa, Yukiharu

1985-01-01

Stability of a hot electron plasma in an NBT(EBT)-like geometry is studied by using a 2-1/2 dimensional relativistic, electromagnetic particle code. For the low-frequency hot electron interchange mode, comparison of the simulation results with the analytical predictions of linear stability theory show fairly good agreement with the magnitude of the growth rates calculated without hot electron finite Larmor radius effects. Strong stabilizing effects by finite Larmor radius of the hot electrons are observed for short wavelength modes. As for the high-frequency hot electron interchange mode, there is a discrepancy between the simulation results and the theory. The high-frequency instability is not observed though a parameter regime is chosen in which the high-frequency hot electron interchange mode is theoretically predicted to grow. Strong cross-field diffusion in a poloidal direction of the hot electrons might explain the stability. Each particle has a magnetic drift velocity, and the speed of the magnetic drift is proportional to the kinetic energy of each particle. Hence, if the particles have high temperature, the spread of the magnetic drift velocity is large. This causes a strong cross-field diffusion of the hot electrons. In the simulation for this interchange mode, an enhanced temperature relaxation is observed between the hot and cold electrons although the theoretically predicted high frequency modes are stable. (Nogami, K.)

Electron impact study of potassium hydroxide

International Nuclear Information System (INIS)

Vuskovic, L.; Trajmar, S.

1979-01-01

An ''elastic'' scattering study for low impact energies (5--20 ev) is reported for electron impact excitation of KOH. The ''elastic'' scattering is regarded as the sum of elastic rotational and vibrational contributions to the scattering

Study of fast electrons from hard-X radiation

International Nuclear Information System (INIS)

Arslanbekov, R.

1995-01-01

The goal of this thesis is the study of fast electron dynamics by means of the hard X-ray diagnosis installed in TORE SUPRA and numerical simulations. Fast electrons are generated in the plasma in the presence of the injected lower hybrid (LH) waves. Two aspects are studied in detail: the lower hybrid wave propagation and absorption in a periodically perturbed media and 2-D Fokker-Planck modelling of the fast electron dynamics in the presence of the LH power. Ripple effects on lower hybrid wave propagation and absorption are investigated using the ray tracing technique. A cylindrical equilibrium is first studied and a strong modification of the ray dynamics is predicted. Calculations are carried out in a real toroidal geometry corresponding to TORE SUPRA. It is shown that the lack of toroidal axisymmetry of the magnetic field may result in a modification of the ray evolution even if the global ray evolution is governed by the larger poloidal inhomogeneity. Simulation of LH experiments are performed for TORE SUPRA tokamak which has a large magnetic ripple (7% at the plasma edge). By considering ripple perturbation in LH current drive simulations, a better agreement is found with experimental results, in particular with the hard-X spectra and the current density profiles. In the second part of the thesis, a 2-D modeling of the fast electron dynamics in the velocity phase space is considered, based on the 2-D relativistic electron Fokker-Planck equation. Electron distribution functions obtained are used to calculate non-thermal Bremsstrahlung emission for different TORE SUPRA shots in a wide range of experimental conditions. (J.S.). 168 refs., 93 figs., 1 tab., 3 appendix

Electron microscopy methods in studies of cultural heritage sites

Energy Technology Data Exchange (ETDEWEB)

Vasiliev, A. L., E-mail: a.vasiliev56@gmail.com; Kovalchuk, M. V.; Yatsishina, E. B. [National Research Centre “Kurchatov Institute” (Russian Federation)

2016-11-15

The history of the development and application of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray microanalysis (EDXMA) in studies of cultural heritage sites is considered. In fact, investigations based on these methods began when electron microscopes became a commercial product. Currently, these methods, being developed and improved, help solve many historical enigmas. To date, electron microscopy combined with microanalysis makes it possible to investigate any object, from parchment and wooden articles to pigments, tools, and objects of art. Studies by these methods have revealed that some articles were made by ancient masters using ancient “nanotechnologies”; hence, their comprehensive analysis calls for the latest achievements in the corresponding instrumental methods and sample preparation techniques.

Electron microscopy methods in studies of cultural heritage sites

International Nuclear Information System (INIS)

Vasiliev, A. L.; Kovalchuk, M. V.; Yatsishina, E. B.

2016-01-01

The history of the development and application of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray microanalysis (EDXMA) in studies of cultural heritage sites is considered. In fact, investigations based on these methods began when electron microscopes became a commercial product. Currently, these methods, being developed and improved, help solve many historical enigmas. To date, electron microscopy combined with microanalysis makes it possible to investigate any object, from parchment and wooden articles to pigments, tools, and objects of art. Studies by these methods have revealed that some articles were made by ancient masters using ancient “nanotechnologies”; hence, their comprehensive analysis calls for the latest achievements in the corresponding instrumental methods and sample preparation techniques.

Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828 formulation and coadministered telmisartan and S-amlodipine in healthy subjects

Directory of Open Access Journals (Sweden)

Kang WY

2018-03-01

concomitantly administered, respectively. The mean Cmax and AUC0–t values of S-amlodipine were 2.71 ng/mL and 130.69 ng⋅h/mL for the FDC, and 2.74 ng/mL and 129.81 ng⋅h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR and 90% confidence interval (CI for the telmisartan Cmax and AUC0–t (FDC of telmisartan and S-amlodipine/concomitant administration were 0.8509 (0.7353–0.9846 and 0.9431 (0.8698–1.0226, respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0–t (FDC/concomitant administration were 0.9829 (0.9143–1.0567 and 0.9632 (0.8798–1.0546, respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion: CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments. Keywords: fixed-dose combination, pharmacokinetics, S-amlodipine, telmisartan, safety

Early studies of placental ultrastructure by electron microscopy

DEFF Research Database (Denmark)

Carter, A M; Enders, A C

2016-01-01

many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University......BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted...

Studies on keV and eV electrons in solids

International Nuclear Information System (INIS)

Schou, J.

1979-10-01

The interaction between keV or eV electrons and solids was studied. The results presented mostly concern problems in connection with electron irradiation of solids, but to some extent they also include ion-induced secondary electron emission. The experiments were mainly performed on solidified gases using 1 - 3 keV electrons. The projected range of electrons was determined in solid hydrogen, deuterium and nitrogen. The true secondary electron emission coefficient and the electron reflection coefficient of solid hydrogen, deuterium and nitrogen were measured. The escape depth of the true secondary electrons in nitrogen was determined. The angular dependence of both the reflection coefficient and the true secondary electron emission coefficient of solid hydrogen and deuterium was investigated. Both ion- and electron-induced secondary electron emission were treated theoretically on the basis of ionization cascade theory. (Auth.)

Contribution to the study of electron paramagnetic resonance and relaxation

International Nuclear Information System (INIS)

Theobald, Jean-Gerard

1962-01-01

This research thesis reports an experimental work which comprises the development of a very practical and very sensitive electron paramagnetic resonance spectrometer, and the use of this equipment for the study of irradiated substances and carbons. By studying electronic resonance signals by fast modulation of the magnetic field, the author studied phenomena of quick passage in electronic resonance, and showed that the study of these phenomena requires observation systems with a particularly large bandwidth. He reports the measurement of the line width of packs of spins of inhomogeneous lines by two different methods [fr

Optical studies of polarized-electron-noble-gas collisions

International Nuclear Information System (INIS)

Gay, T.I.; Furst, J.E.; Geesmann, H.; Khakoo, M.A.; Madison, D.H.; Wijayaratna, W.M.K.P.; Bartschat, K.

1992-01-01

We have measured the Stoke's parameters of light emitted following impact excitation of He and Xe by transversely-polarized electrons. For He, the 2 3 S-3 3 P, 389 nm transition was studied in an effort to systematically develop a highly accurate optical electron polarimeter. The 6 3 P 2 -6 3 D 3 , 882 nm transition in Xe was used to assess the importance of spin-dependent forces on the continuum electron for this target. We attempted (and failed) to made the first optical observations of Mott scattering. (Author)

Studies on electron transfer reactions of Keggin-type mixed ...

Indian Academy of Sciences (India)

Administrator

(PV2) in aqueous phosphate buffer of pH 6 at ambient temperature. Electrochemical and optical studies show that the stoichiometry of the reaction is 1: 2 (NADH : HPA). EPR and optical studies show that HPA act as one electron acceptor and the products of electron transfer reactions are one elec- tron reduced heteropoly ...

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

Science.gov (United States)

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

2012-10-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

Penning ionization processes studied by electron spectroscopy

International Nuclear Information System (INIS)

Yencha, A.J.

1978-01-01

The technique of measuring the kinetic energy of electrons ejected from atomic or molecular species as a result of collisional energy transfer between a metastable excited rare gas atom and an atom or molecule is known as Penning ionization spectroscopy. Like the analogous photoionization process of photoelectron spectroscopy, a considerable amount of information has been gained about the ionization potentials of numerous molecular systems. It is, in fact, through the combined analyses of photoelectron and Penning electron spectra that affords a probe of the particle-particle interactions that occur in the Penning process. In this paper a short survey of the phenomenon of Penning ionization, as studied by electron spectroscopy, will be presented as it pertains to the ionization processes of simple molecules by metastable excited atoms. (author)

Spin dynamics of electrons in strong fields studied via bremsstrahlung from a polarized electron beam

Energy Technology Data Exchange (ETDEWEB)

Tashenov, Stanislav [Royal Institute of Technology, Stockholm (Sweden); Stockholm University (Sweden); Physikalisches Institut, Universitaet Heidelberg (Germany); Baeck, Torbjoern; Cederwall, Bo; Khaplanov, Anton; Schaessburger, Kai-Uwe [Royal Institute of Technology, Stockholm (Sweden); Barday, Roman; Enders, Joachim; Poltoratska, Yuliya [Institut fuer Kernphysik, Technische Universitaet, Darmstadt (Germany); Surzhykov, Andrey [Physikalisches Institut, Universitaet Heidelberg (Germany); GSI, Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany)

2011-07-01

Linear polarization of the photons emitted in the process of the atomic field electron bremsstrahlung has been studied at the newly developed 100 keV polarized electron source of TU Darmstadt. A correlation between the initial orientation of the electron spin and the degree and the angle of photon linear polarization has been measured for the first time. For this purpose a hard x-ray Compton polarimeter consisting of a segmented high purity germanium detector and an external passive photon scattering target have been applied. Linear polarization sensitive Compton and Rayleigh photon scattering distributions have been sampled by the segmented detector. The observed polarization correlation reveals a precession of the electron spin as it moves in the field of the nucleus. The full-relativistic calculations for the case of radiative recombination into a Rydberg series limit have been corroborated by the measurement. The results of this experiment suggest a new method for electron beam polarimetry.

Fabrication and electronic transport studies of single nanocrystal systems

Energy Technology Data Exchange (ETDEWEB)

Klein, David Louis [Univ. of California, Berkeley, CA (United States). Dept. of Physics

1997-05-01

Semiconductor and metallic nanocrystals exhibit interesting electronic transport behavior as a result of electrostatic and quantum mechanical confinement effects. These effects can be studied to learn about the nature of electronic states in these systems. This thesis describes several techniques for the electronic study of nanocrystals. The primary focus is the development of novel methods to attach leads to prefabricated nanocrystals. This is because, while nanocrystals can be readily synthesized from a variety of materials with excellent size control, means to make electrical contact to these nanocrystals are limited. The first approach that will be described uses scanning probe microscopy to first image and then electrically probe surfaces. It is found that electronic investigations of nanocrystals by this technique are complicated by tip-sample interactions and environmental factors such as salvation and capillary forces. Next, an atomic force microscope technique for the catalytic patterning of the surface of a self assembled monolayer is described. In principle, this nano-fabrication technique can be used to create electronic devices which are based upon complex arrangements of nanocrystals. Finally, the fabrication and electrical characterization of a nanocrystal-based single electron transistor is presented. This device is fabricated using a hybrid scheme which combines electron beam lithography and wet chemistry to bind single nanocrystals in tunneling contact between closely spaced metallic leads. In these devices, both Au and CdSe nanocrystals show Coulomb blockade effects with characteristic energies of several tens of meV. Additional structure is seen the transport behavior of CdSe nanocrystals as a result of its electronic structure.

Studies of runaway electrons via Cherenkov effect in tokamaks

Science.gov (United States)

Zebrowski, J.; Jakubowski, L.; Rabinski, M.; Sadowski, M. J.; Jakubowski, M. J.; Kwiatkowski, R.; Malinowski, K.; Mirowski, R.; Mlynar, J.; Ficker, O.; Weinzettl, V.; Causa, F.; COMPASS; FTU Teams

2018-01-01

The paper concerns measurements of runaway electrons (REs) which are generated during discharges in tokamaks. The control of REs is an important task in experimental studies within the ITER-physics program. The NCBJ team proposed to study REs by means of Cherenkov-type detectors several years ago. The Cherenkov radiation, induced by REs in appropriate radiators, makes it possible to identify fast electron beams and to determine their spatial- and temporal-characteristics. The results of recent experimental studies of REs, performed in two tokamaks - COMPASS in Prague and FTU in Frascati, are summarized and discussed in this paper. Examples of the electron-induced signals, as recorded at different experimental conditions and scenarios, are presented. Measurements performed with a three-channel Cherenkov-probe in COMPASS showed that the first fast electron peaks can be observed already during the current ramp-up phase. A strong dependence of RE-signals on the radial position of the Cherenkov probe was observed. The most distinct electron peaks were recorded during the plasma disruption. The Cherenkov signals confirmed the appearance of post-disruptive RE beams in circular-plasma discharges with massive Ar-puffing. During experiments at FTU a clear correlation between the Cherenkov detector signals and the rotation of magnetic islands was identified.

Inter-professional electronic documents and child health: a study of persisting non-electronic communication in the use of electronic documents.

Science.gov (United States)

Saario, Sirpa; Hall, Christopher; Peckover, Sue

2012-12-01

Information and communication technologies are widely used in health and social care settings to replace previous means of record keeping, assessment and communication. Commentary on the strengths and weaknesses of such systems abound, thus it is useful to examine how they are used in practice. This article draws on findings from two separate studies, conducted between 2005 and 2007, which examined how child health and welfare professionals use electronic documents in Finland and England. Known respectively as Miranda and CAF, these systems are different in terms of structure and function but in their everyday use common features are identified, notably the continued use of and reliance on non-electronic means of communication. Based on interviews with professionals, three forms of non-electronic communication are described: alternative records, phone calls and letters, which facilitate the sharing of the electronic record. Finally, the electronic documents are further analysed as potential boundary objects which aim to create common understanding between sites and professionals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ion and electron swarm studies of relevance to plasma processing: positive ion-molecule and electron-molecule studies of SF6 and derivatives

International Nuclear Information System (INIS)

Atterbury, C.; Kennedy, R.A.; Critchley, A.D.J.; Mayhew, C.A.

2002-01-01

Many sequential and parallel chemical reactions involving charged species occur in a plasma. Data needed to model plasma's chemical and physical environment includes cross-section, rate coefficients, and product ion distribution of electron-molecule and ion-molecule processes. Such reactions are studied by our group away from the complexity of the plasma environment, with experimental techniques that allow us to concentrate on a single process, where usually only one or two species are involved. A molecule commonly used in plasma etching applications is SF 6 1,2 . We have performed a series of positive ion-molecule and electron attachment studies on SF 6 and related molecules, including SeF 6 , TeF 6 (i.e. XF 6 molecules), SF 5 CF 3 and SF 5 Cl (i.e. SF 5 X molecules) 3- (. The studies of ion reactions with and electron attachment to SF 6 and physically similar molecules are of value when seeking to understand the ion and electron chemistry occurring in SF 6 containing plasma. The result of these studies are presented in this poster. Ion-molecule reactions. Rate coefficients and ion product branching ratios have been determined with the Selected Ion Flow Tube (SIFT) at room temperature (300 K) for reactions of SF 5 X with the following twenty-two cations; Ne + , F + , Ar + , N 2 + , N + , CO + , CO 2 + , O + , N 2 O + , O 2 + , SF 4 + , CF 2 + , SF + , SF 2 + , NO 2 + , SF 5 + , NO + , CF + , CF 3 + , SF 3 + , and H 3 O + (listed in order of decreasing recombination energy). SF 2 + , NO 2 + , NO + , SF 3 + , and H 3 O + are found to be unreacted with both SF 5 CF 3 and SF 5 Cl. The majority of the other reactions proceed with rate coefficients that are close to the capture value. Those found to occur at rates significantly less than the capture mechanism value re the reactions of O 2 + , SF + , SF 5 + , and CF 3 + with SF 5 CF 3 , and SF 4 + and SF 5 + with SF 5 Cl. Several distinction processes are observed among the large number of reactions studied, including

Theoretical study of lithium clusters by electronic stress tensor

International Nuclear Information System (INIS)

Ichikawa, Kazuhide; Nozaki, Hiroo; Komazawa, Naoya; Tachibana, Akitomo

2012-01-01

We study the electronic structure of small lithium clusters Li_n (n = 2 ∼ 8) using the electronic stress tensor. We find that the three eigenvalues of the electronic stress tensor of the Li clusters are negative and degenerate, just like the stress tensor of liquid. This leads us to propose that we may characterize a metallic bond in terms of the electronic stress tensor. Our proposal is that in addition to the negativity of the three eigenvalues of the electronic stress tensor, their degeneracy characterizes some aspects of the metallic nature of chemical bonding. To quantify the degree of degeneracy, we use the differential eigenvalues of the electronic stress tensor. By comparing the Li clusters and hydrocarbon molecules, we show that the sign of the largest eigenvalue and the differential eigenvalues could be useful indices to evaluate the metallicity or covalency of a chemical bond.

Electron cloud studies for SIS-18 and for the FAIR synchrotrons

Energy Technology Data Exchange (ETDEWEB)

Petrov, Fedor; Weiland, Thomas [Technische Universitaet Darmstadt, Institut fuer Theorie Elektromagnetischer Felder (TEMF), Darmstadt (Germany); Boine-Frankenheim, Oliver [Gesellschaft fuer Schwerionenforschung (GSI) GmbH, Darmstadt (Germany)

2010-07-01

Electron clouds generated by residual gas ionization pose a potential threat to the stability of the circulating heavy ion beams in the existing SIS-18 synchrotron and in the projected SIS-100. The electrons can potentially accumulate in the space charge potential of the long bunches. As an extreme case we study the accumulation of electrons in a coasting beam under conditions relevant in the SIS-18. Previous studies of electron clouds in coasting beams used particle-in-cell (PIC) codes to describe the generation of the cloud and the interaction with the ion beam. PIC beams exhibit much larger fluctuation amplitudes than real beams. The fluctuations heat the electrons. Therefore the obtained neutralization degree is strongly reduced, relative to a real beam. In our simulation model we add a Langevin term to the electron equation of motion in order to account for the heating process. The effect of natural beam fluctuations on the neutralization degree is studied. The modification of the beam response function as well as the stability limits in the presence of the electrons is discussed.

Polarization Studies for the eRHIC Electron Storage Ring

Energy Technology Data Exchange (ETDEWEB)

Gianfelice-Wendt, Eliana [Fermilab; Tepikian, S. [Brookhaven

2018-04-01

A hadron/lepton collider with polarized beams has been under consideration by the scientific community since some years, in the U.S. and Europe. Among the various proposals, those by JLAB and BNL with polarized electron and proton beams are currently under closer study in the U.S. Experimenters call for the simultaneous storage of electron bunches with both spin helicity. In the BNL based Ring-Ring design, electrons are stored at top energy in a ring to be accommodated in the existing RHIC tunnel. The transversely polarized electron beam is injected into the storage ring at variable energies, between 5 and 18 GeV. Polarization is brought into the longitudinal direction at the IP by a couple of spin rotators. In this paper results of first studies of the attainable beam polarization level and lifetime in the storage ring at 18 GeV are presented.

Advanced Electron Holography Applied to Electromagnetic Field Study in Materials Science.

Science.gov (United States)

Shindo, Daisuke; Tanigaki, Toshiaki; Park, Hyun Soon

2017-07-01

Advances and applications of electron holography to the study of electromagnetic fields in various functional materials are presented. In particular, the development of split-illumination electron holography, which introduces a biprism in the illumination system of a holography electron microscope, enables highly accurate observations of electromagnetic fields and the expansion of the observable area. First, the charge distributions on insulating materials were studied by using split-illumination electron holography and including a mask in the illumination system. Second, the three-dimensional spin configurations of skyrmion lattices in a helimagnet were visualized by using a high-voltage holography electron microscope. Third, the pinning of the magnetic flux lines in a high-temperature superconductor YBa 2 Cu 3 O 7-y was analyzed by combining electron holography and scanning ion microscopy. Finally, the dynamic accumulation and collective motions of electrons around insulating biomaterial surfaces were observed by utilizing the amplitude reconstruction processes of electron holography. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modified Monte Carlo method for study of electron transport in degenerate electron gas in the presence of electron–electron interactions, application to graphene

International Nuclear Information System (INIS)

Borowik, Piotr; Thobel, Jean-Luc; Adamowicz, Leszek

2017-01-01

Standard computational methods used to take account of the Pauli Exclusion Principle into Monte Carlo (MC) simulations of electron transport in semiconductors may give unphysical results in low field regime, where obtained electron distribution function takes values exceeding unity. Modified algorithms were already proposed and allow to correctly account for electron scattering on phonons or impurities. Present paper extends this approach and proposes improved simulation scheme allowing including Pauli exclusion principle for electron–electron (e–e) scattering into MC simulations. Simulations with significantly reduced computational cost recreate correct values of the electron distribution function. Proposed algorithm is applied to study transport properties of degenerate electrons in graphene with e–e interactions. This required adapting the treatment of e–e scattering in the case of linear band dispersion relation. Hence, this part of the simulation algorithm is described in details.

Modified Monte Carlo method for study of electron transport in degenerate electron gas in the presence of electron–electron interactions, application to graphene

Energy Technology Data Exchange (ETDEWEB)

Borowik, Piotr, E-mail: pborow@poczta.onet.pl [Warsaw University of Technology, Faculty of Physics, ul. Koszykowa 75, 00-662 Warszawa (Poland); Thobel, Jean-Luc, E-mail: jean-luc.thobel@iemn.univ-lille1.fr [Institut d' Electronique, de Microélectronique et de Nanotechnologies, UMR CNRS 8520, Université Lille 1, Avenue Poincaré, CS 60069, 59652 Villeneuve d' Ascq Cédex (France); Adamowicz, Leszek, E-mail: adamo@if.pw.edu.pl [Warsaw University of Technology, Faculty of Physics, ul. Koszykowa 75, 00-662 Warszawa (Poland)

2017-07-15

Standard computational methods used to take account of the Pauli Exclusion Principle into Monte Carlo (MC) simulations of electron transport in semiconductors may give unphysical results in low field regime, where obtained electron distribution function takes values exceeding unity. Modified algorithms were already proposed and allow to correctly account for electron scattering on phonons or impurities. Present paper extends this approach and proposes improved simulation scheme allowing including Pauli exclusion principle for electron–electron (e–e) scattering into MC simulations. Simulations with significantly reduced computational cost recreate correct values of the electron distribution function. Proposed algorithm is applied to study transport properties of degenerate electrons in graphene with e–e interactions. This required adapting the treatment of e–e scattering in the case of linear band dispersion relation. Hence, this part of the simulation algorithm is described in details.

Electron-ion recombination study in argon at atmospheric pressure

International Nuclear Information System (INIS)

Kafrouni, Hanna.

1979-01-01

This study deals with a wall-stabilized arc burning in argon at atmospheric pressure. A transient mode is obtained using a fast thyristor connected to the electrodes, which short-circuits the discharge. By means of two wavelengths laser interferometry and spectroscopy measurements we have determined the temporal changes of the electron density, ground state atom density and excited atom density. We have shown that, when the electric field is suppressed, the electron temperature rapidly decreases to the gas temperature before changing electron and atom densities. This phenomenon is applied to determine the gas temperature and to evaluate the role played by ionization in electron density balance. The coefficients of ambipolar diffusion, ionization and recombination and an apparent recombination coefficient are determined versus electron temperature and compared with theoretical values [fr

Experimental study of fast electron transport in dense plasmas

International Nuclear Information System (INIS)

Vaisseau, Xavier

2014-01-01

The framework of this PhD thesis is the inertial confinement fusion for energy production, in the context of the electron fast ignition scheme. The work consists in a characterization of the transport mechanisms of fast electrons, driven by intense laser pulses (10 19 - 10 20 W/cm 2 ) in both cold-solid and warm-dense matter. The first goal was to study the propagation of a fast electron beam, characterized by a current density ≥ 10 11 A/cm 2 , in aluminum targets initially heated close to the Fermi temperature by a counter-propagative planar shock. The planar compression geometry allowed us to discriminate the energy losses due to the resistive mechanisms from collisional ones by comparing solid and compressed targets of the same initial areal densities. We observed for the first time a significant increase of resistive energy losses in heated aluminum samples. The confrontation of the experimental data with the simulations, including a complete characterization of the electron source, of the target compression and of the fast electron transport, allowed us to study the time-evolution of the material resistivity. The estimated resistive electron stopping power in a warm-compressed target is of the same order as the collisional one. We studied the transport of the fast electrons generated in the interaction of a high-contrast laser pulse with a hollow copper cone, buried into a carbon layer, compressed by a counter-propagative planar shock. A X-ray imaging system allowed us to visualize the coupling of the laser pulse with the cone at different moments of the compression. This diagnostic, giving access to the fast electron spatial distribution, showed a fast electron generation in the entire volume of the cone for late times of compression, after shock breakout from the inner cone tip. For earlier times, the interaction at a high-contrast ensured that the source was contained within the cone tip, and the fast electron beam was collimated into the target depth by

Electronic conductivity studies on oxyhalide glasses containing TMO

Energy Technology Data Exchange (ETDEWEB)

Vijayatha, D. [R& D Center, Bharatiar University, Coimbatore, Tamil Nadu (India); Department of Physics, Gurunanak Institute of Technology, Hyderabad -040 (India); Viswanatha, R. [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India); Sujatha, B. [Department of Electronics and Communcation, MSRIT, Bangalore 560054 (India); Narayana Reddy, C., E-mail: nivetejareddy@gmail.com [Department of Physics, Sree Siddaganga College of Arts, Science and Commerce, Tumkur 572102 (India)

2016-05-06

Microwave-assisted synthesis is cleaner, more economical and much faster than conventional methods. The development of new routes for the synthesis of solid materials is an integral part of material science and technology. The electronic conductivity studies on xPbCl{sub 2} – 60 PbO – (40-x) V{sub 2}O{sub 5} (1 ≥ x ≤ 10) glass system has been carried out over a wide range of composition and temperature (300 K to 423 K). X-ray diffraction study confirms the amorphous nature of the samples. The Scanning electron microscopic studies reveal the formation of cluster like morphology in PbCl{sub 2} containing glasses. The d.c conductivity exhibits Arrhenius behaviour and increases with V{sub 2}O{sub 5} concentration. Analysis of the results is interpreted in view Austin-Mott’s small polaron model of electron transport. Activation energies calculated using regression analysis exhibit composition dependent trend and the variation is explained in view of the structure of lead-vanadate glass.

Experimental studies of electron capture

International Nuclear Information System (INIS)

Pedersen, E.H.

1983-01-01

This thesis discusses the main results of recent experimental studies of electron capture in asymmetric collisions. Most of the results have been published, but the thesis also contains yet unpublished data, or data presented only in unrefereed conference proceedings. The thesis aims at giving a coherent discussion of the understanding of the experimental results, based first on simple qualitative considerations and subsequently on quantitative comparisons with the best theoretical calculations currently available. (Auth.)

Theoretical and experimental studies of runaway electrons in the TEXTOR tokamak

International Nuclear Information System (INIS)

Abdullaev, S.S.; Finken, K.H.; Wongrach, K.; Willi, O.

2016-01-01

Theoretical and experimental studies of runaway electrons in tokamaks and their mitigations, particularly the recent studies performed by a group of the Heinrich-Heine University Duesseldorf in collaboration with the Institute of Energy and Climate Research of the Research Centre (Forschungszentrum) of Juelich are reviewed. The main topics focus on (i) runaway generation mechanisms, (ii) runaway orbits in equilibrium plasma, (iii) transport in stochastic magnetic fields, (iv) diagnostics and investigations of transport of runaway electron and their losses in low density discharges (v) runaway electrons during plasma disruptions, and (vi) runaway mitigation methods. The development of runaway diagnostics enables the measurement of runaway electrons in both the centre and edge of the plasma. The diagnostics provide an absolute runaway energy resolved measurement, the radial decay length of runaway electrons and, the structure and dynamics of runaway electron beams. The new mechanism of runaway electron formation during plasma disruptions is discussed.

Theoretical and experimental studies of runaway electrons in the TEXTOR tokamak

Energy Technology Data Exchange (ETDEWEB)

Abdullaev, S.S.; Finken, K.H.; Wongrach, K.; Willi, O.

2016-07-01

Theoretical and experimental studies of runaway electrons in tokamaks and their mitigations, particularly the recent studies performed by a group of the Heinrich-Heine University Duesseldorf in collaboration with the Institute of Energy and Climate Research of the Research Centre (Forschungszentrum) of Juelich are reviewed. The main topics focus on (i) runaway generation mechanisms, (ii) runaway orbits in equilibrium plasma, (iii) transport in stochastic magnetic fields, (iv) diagnostics and investigations of transport of runaway electron and their losses in low density discharges (v) runaway electrons during plasma disruptions, and (vi) runaway mitigation methods. The development of runaway diagnostics enables the measurement of runaway electrons in both the centre and edge of the plasma. The diagnostics provide an absolute runaway energy resolved measurement, the radial decay length of runaway electrons and, the structure and dynamics of runaway electron beams. The new mechanism of runaway electron formation during plasma disruptions is discussed.

Study of electron beam production by a plasma focus

International Nuclear Information System (INIS)

Smith, J.R.; Luo, C.M.; Rhee, M.J.; Schneider, R.F.

1983-01-01

A preliminary investigation of the electron beam produced by a plasma focus device using a current charged transmission line is described. Electron beam currents as high as 10 kA were measured. Interaction of the extracted beam and the filling gas was studied using open shutter photography

Comparative study of electron conduction in azulene and naphthalene

Indian Academy of Sciences (India)

Wintec

tional or electronic devices. Recent advances in experi- mental techniques have allowed ... stimulates us to study the electronic conduction in azulene molecule and to compare that with its isomer, naphthalene. ..... ernment of India, for funding and (SD) acknowledges CSIR,. Government of India, for a research fellowship.

Positron annihilation and electron spin resonance studies of defects in electron-irradiated 3C-SiC

International Nuclear Information System (INIS)

Itoh, Hisayoshi; Yoshikawa, Masahito; Tanigawa, Shoichiro; Nashiyama, Isamu; Misawa, Shunji; Okumura, Hajime; Yoshida, Sadafumi.

1992-01-01

Defects induced by 1 MeV electron-irradiation in cubic silicon carbide (3C-SiC) epitaxially grown by chemical vapor deposition have been studied with positron annihilation and electron spin resonance (ESR). Doppler broadened energy spectra of annihilation γ-rays obtained by using variable-energy positron beams showed the formation of vacancy-type defects in 3C-SiC by the electron-irradiation. An ESR spectrum labeled Tl, which has an isotropic g-value of 2.0029 ± 0.001, was observed in electron-irradiated 3C-SiC. The Tl spectrum is interpreted by hyperfine interactions of paramagnetic electrons with 13 C at four carbon sites and 29 Si at twelve silicon sites, indicating that the Tl center arises from a point defect at a silicon site. Both the results can be accounted for by the introduction of isolated Si vacancies by the irradiation. (author)

Structural studies of glasses by transmission electron microscopy and electron diffraction

International Nuclear Information System (INIS)

Kashchieva, E.P.

1997-01-01

The purpose of this work is to present information about the applications of transmission electron microscopy (TEM) and electron diffraction (ED) for structural investigations of glasses. TEM investigations have been carried out on some binary and on a large number of ternary borate-telluride systems where glass-forming oxides, oxides of transitional elements and modified oxides of elements from I, II and III groups in the periodic table, are used as third component. The large experimental data given by TEM method allows the fine classification of the micro-heterogeneities. A special case of micro-heterogeneous structure with technological origin occurs near the boundary between the 2 immiscible liquids obtained at macro-phase separation. TEM was also used for the direct observation of the glass structure and we have studied the nano-scale structure of borate glasses obtained at slow and fast cooling of the melts. The ED possesses advantages for analysis of amorphous thin films or micro-pastilles and it is a very useful technique for study in materials containing simultaneously light and heavy elements. A comparison between the possibilities of the 3 diffraction techniques (X-ray diffraction, neutron diffraction and ED) is presented

Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

Science.gov (United States)

Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

2010-11-01

Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

Electron gun design study for the IUCF beam cooling system

International Nuclear Information System (INIS)

Friesel, D.L.; Ellison, T.; Jones, W.P.

1985-01-01

The design of a low temperature electron beam cooling system for the Indiana University electron-cooled storage ring is in progress. The storage ring, which will accept the light ion beams from the existing k=200, multi-stage cyclotron facility, requires an electron beam variable in energy from about 7 to 275 keV. The electron beam system consists of a high perveance electron gun with Pierce geometry and a flat cathode. The gun and a 28 element accelerating column are immersed in a uniform longitudinal magnetic guide field. A computer modeling study of the system was conducted to determine electron beam density and transverse temperature variations as a function of anode region and accelerator column design parameters. Transverse electron beam temperatures (E /SUB t/ = mc 2 β 2 γ(/theta/ /SUB H/ +/theta/ /SUB v/ )) of less than a few tenths of an electron volt at a maximum current density of 0.4 A/cm 2 are desired over the full energy range. This was achieved in the calculations without the use of resonant focusing for a 2 Amp, 275 keV electron beam. Some systematics of the electron beam temperature variations with system design parameters are presented. A short discussion of the mechanical design of the proposed electron beam system is also given

A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach.

Science.gov (United States)

Weber, Benjamin; Hochhaus, Guenther

2015-07-01

The role of plasma pharmacokinetics (PK) for assessing bioequivalence at the target site, the lung, for orally inhaled drugs remains unclear. A validated semi-mechanistic model, considering the presence of mucociliary clearance in central lung regions, was expanded for quantifying the sensitivity of PK studies in detecting differences in the pulmonary performance (total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics) between test (T) and reference (R) inhaled fluticasone propionate (FP) products. PK bioequivalence trials for inhaled FP were simulated based on this PK model for a varying number of subjects and T products. The statistical power to conclude bioequivalence when T and R products are identical was demonstrated to be 90% for approximately 50 subjects. Furthermore, the simulations demonstrated that PK metrics (area under the concentration time curve (AUC) and C max) are capable of detecting differences between T and R formulations of inhaled FP products when the products differ by more than 20%, 30%, and 25% for total lung deposition, central-to-peripheral lung deposition ratio, and pulmonary dissolution characteristics, respectively. These results were derived using a rather conservative risk assessment approach with an error rate of <10%. The simulations thus indicated that PK studies might be a viable alternative to clinical studies comparing pulmonary efficacy biomarkers for slowly dissolving inhaled drugs. PK trials for pulmonary efficacy equivalence testing should be complemented by in vitro studies to avoid false positive bioequivalence assessments that are theoretically possible for some specific scenarios. Moreover, a user-friendly web application for simulating such PK equivalence trials with inhaled FP is provided.

NMR studies of transmembrane electron transport in human erythrocytes

International Nuclear Information System (INIS)

Kennett, E.C.; Bubb, W.A.; Kuchel, P.W.

2002-01-01

Full text: Electron transport systems exist in the plasma membranes of all cells. These systems appear to play a role in cell growth and proliferation, intracellular signalling, hormone responses, apoptotic events, cell defence and perhaps most importantly they enable the cell to respond to changes in the redox state of both the intra- and extracellular environments. Previously, 13 C NMR has been used to study transmembrane electron transport in human erythrocytes, specifically the reduction of extracellular 13 C-ferricyanide. NMR is a particularly useful tool for studying such systems as changes in the metabolic state of the cell can be observed concomitantly with extracellular reductase activity. We investigated the oxidation of extracellular NADH by human erythrocytes using 1 H and 31 P NMR spectroscopy. Recent results for glucose-starved human erythrocytes indicate that, under these conditions, extracellular NADH can be oxidised at the plasma membrane with the electron transfer across the membrane resulting in reduction of intracellular NAD + . The activity is inhibited by known trans-plasma membrane electron transport inhibitors (capsaicin and atebrin) and is unaffected by inhibition of the erythrocyte Band 3 anion transporter. These results suggest that electron import from extracellular NADH allows the cell to re-establish a reducing environment after the normal redox balance is disturbed

Optimization of power output and study of electron beam energy spread in a Free Electron Laser oscillator

CERN Document Server

Abramovich, A; Efimov, S; Gover, A; Pinhasi, Y; Yahalom, A

2001-01-01

Design of a multi-stage depressed collector for efficient operation of a Free Electron Laser (FEL) oscillator requires knowledge of the electron beam energy distribution. This knowledge is necessary to determine the voltages of the depressed collector electrodes that optimize the collection efficiency and overall energy conversion efficiency of the FEL. The energy spread in the electron beam is due to interaction in the wiggler region, as electrons enter the interaction region at different phases relative to the EM wave. This interaction can be simulated well by a three-dimensional simulation code such as FEL3D. The main adjustable parameters that determine the electron beam energy spread after interaction are the e-beam current, the initial beam energy, and the quality factor of the resonator out-coupling coefficient. Using FEL3D, we study the influence of these parameters on the available radiation power and on the electron beam energy distribution at the undulator exit. Simulations performed for I=1.5 A, E...

Study and impact of fast electrons diagnosed by electron cyclotron radiation on Tore-Supra tokamak

International Nuclear Information System (INIS)

Gomez, P.

1999-12-01

This thesis aims at characterizing the dynamics of fast electrons generated by the Landau absorption of the hybrid wave and studying their effects on electron cyclotron radiation. The different processes involved in the propagation and resonant absorption of the hybrid wave in plasmas are described. A method such as ray-tracing allows the characterization of the dynamics of heating but this method relies on the hypothesis of geometrical optics. Whenever absorption rate is low as it is in Tore-Supra, the hybrid wave undergoes a series of successive reflections on the edge of the plasma before being completely absorbed. These reflections generate an electromagnetic chaos in which geometrical optics hypothesis are no longer valid. A statistical treatment of the Fokker-Planck equation allows the calculation of the mean distribution function of electrons in the plasma submitted to hybrid wave. The electron cyclotron radiation is then deduced and by assuming that plasma behaves like a black body, a theoretical radiative temperature is calculated. The confrontation of this theoretical temperature profile with experimental values allows the validation of this modeling and the estimation of the effects of fast electrons on temperature measurements. (A.C.)

A design study of non-adiabatic electron guns

International Nuclear Information System (INIS)

Barroso, J.J.; Stellati, C.

1994-01-01

The design of a non-adiabatic gun capable of producing a 10 A, 50 KeV high-quality laminar electron beam is reported. In contrast to the magnetron injection gun with a conical cathode, where the beam is generated initially with a transverse velocity component, in the non-adiabatic gun electrons are extracted in a direction parallel to the axial guide magnetic field. The beam electrons acquire cyclotron motion as result of non-adiabatic processes in a strong non uniform electric field across the modulation anode. Such an extraction method gives rise to favourable features that are explored throughout the work. An extensive numerical simulation study has also been done to minimize velocity and energy spreads. (author). 3 refs, 5 figs, 1 tab

Study of the electronic structure of pure aluminium, aluminium oxide and nitride by spectroscopy of electrons excited under electronic and photonic bombardment (X and UV)

International Nuclear Information System (INIS)

Gautier-Soyer, Martine

1985-01-01

This research thesis reports the use of electron spectroscopy with electrons excited under electronic or photonic (X or UV) bombardment for the study of electronic state density of aluminium, aluminium oxide (Al 2 O 3 ) and aluminium nitride (AlN). The objective is to get an insight into phenomena related to technological problems of adherence, wear, lubrication, corrosion or breakdown met in metals, insulators and semiconductors. The author highlighted the presence of occupied surface states on Al(111) and Al(100), and electronic levels localised in the forbidden band of Al 2 O 3 and AlN, induced by structural defects which promote surface reactivity [fr

Study of the electrons elastic scattering by atoms through pseudopotentials

International Nuclear Information System (INIS)

Bettega, M.H.F.

1990-01-01

Pseudopotentials allow an extraordinary simplification in the calculation of the electronic structure of atoms, molecules and crystals. Though they have been used extensively for electronic structure calculations, little is known of their applicability to scattering. A study of the pseudopotentials of Bachelet, Hamann and Schuter in the electron scattering by atoms was made, calculating phase-shifts and cross sections for angular momenta 1=0,1 and 2 and energy up to 5 R y. The results for the pseudopotential were compared all-electron calculations. The agreement is very good in a broad energy band. A simplification of the calculation of scattering by complex molecules where an all-electron calculation is impossible is aimed. (author)

Simulation study of secondary electron images in scanning ion microscopy

CERN Document Server

Ohya, K

2003-01-01

The target atomic number, Z sub 2 , dependence of secondary electron yield is simulated by applying a Monte Carlo code for 17 species of metals bombarded by Ga ions and electrons in order to study the contrast difference between scanning ion microscopes (SIM) and scanning electron microscopes (SEM). In addition to the remarkable reversal of the Z sub 2 dependence between the Ga ion and electron bombardment, a fine structure, which is correlated to the density of the conduction band electrons in the metal, is calculated for both. The brightness changes of the secondary electron images in SIM and SEM are simulated using Au and Al surfaces adjacent to each other. The results indicate that the image contrast in SIM is much more sensitive to the material species and is clearer than that for SEM. The origin of the difference between SIM and SEM comes from the difference in the lateral distribution of secondary electrons excited within the escape depth.

Contribution of scanning Auger microscopy to electron beam damage study

International Nuclear Information System (INIS)

Fontaine, J.M.

1983-04-01

Electron bombardment can produce surface modifications of the analysed sample. The electron beam effects on solid surfaces which have been discussed in the published literature can be classified into the following four categories: (1) heating and its consequent effects, (2) charge accumulation in insulators and its consequent effects, (3) electron stimulated adsorption (ESA), and (4) electron stimulated desorption and/or decomposition (ESD). In order to understand the physico-chemical processes which take place under electron irradiation in an Al-O system, we have carried out experiments in which, effects, such as heating, charging and gas contamination, were absent. Our results point out the role of an enhanced surface diffusion of oxygen during electron bombardment of an Al (111) sample. The importance of this phenomenon and the contribution of near-elastic scattering of the primary electrons (5 keV) to the increase of the oxidation degree observed on Al (111) are discussed, compared to the generally studied effects

Study of electron temperature evolution during sawtoothing and pellet injection using thermal electron cyclotron emission in the Alcator C tokamak

International Nuclear Information System (INIS)

Gomez, C.C.

1986-05-01

A study of the electron temperature evolution has been performed using thermal electron cyclotron emission. A six channel far infrared polychromator was used to monitor the radiation eminating from six radial locations. The time resolution was <3 μs. Three events were studied, the sawtooth disruption, propagation of the sawtooth generated heatpulse and the electron temperature response to pellet injection. The sawtooth disruption in Alcator takes place in 20 to 50 μs, the energy mixing radius is approx. 8 cm or a/2. It is shown that this is inconsistent with single resonant surface Kadomtsev reconnection. Various forms of scalings for the sawtooth period and amplitude were compared. The electron heatpulse propagation has been used to estimate chi e(the electron thermal diffusivity). The fast temperature relaxation observed during pellet injection has also been studied. Electron temperature profile reconstructions have shown that the profile shape can recover to its pre-injection form in a time scale of 200 μs to 3 ms depending on pellet size

Silicon passivation study under low energy electron irradiation conditions

International Nuclear Information System (INIS)

Cluzel, R.

2010-01-01

Backside illuminated thinned CMOS (Complementary Metal Oxide Semiconductor) imaging system is a technology developed to increase the signal to noise ratio and the sensibility of such sensors. This configuration is adapted to the electrons detection from the energy range of [1 - 12 keV]. The impinging electron creates by multiplication several hundreds of secondary electrons close to the surface. A P ++ highly-doped passivation layer of the rear face is required to reduce the secondary electron surface recombination rate. Thanks to the potential barrier induced by the P ++ layer, the passivation layer increases the collected charges number and so the sensor collection gain. The goal of this study is to develop some experimental methods in order to determine the effect of six different passivation processes on the collection gain. Beforehand, the energy profile deposited by an incident electron is studied with the combination of Monte-Carlo simulations and some analytical calculations. The final collection gain model shows that the mirror effect from the passivation layer is a key factor at high energies whereas the passivation layer has to be as thin as possible at low energies. A first experimental setup which consists in irradiating P ++ /N large diodes allows to study the passivation process impacts on the surface recombinations. Thanks to a second setup based on a single event upset directly on thinned CMOS sensor, passivation techniques are discriminated in term of mirror effect and the implied spreading charges. The doping atoms activation laser annealing is turn out to be a multiplication gain inhomogeneity source impacting directly the matrix uniformity. (author)

Desorption of hydrogen from magnesium hydride: in-situ electron diffraction study

International Nuclear Information System (INIS)

Paik, B.; Jones, I.P.; Walton, A.; Mann, V.; Book, D.; Harris, I.R.

2009-01-01

The dynamics of a phase change has been studied where electron beam in Transmission Electron Microscope (TEM) has been used to transform MgH 2 into magnesium. A combination of in-situ Electron Diffraction (ED) and an in-situ Electron Energy Loss Spectroscopy (EELS) study under ED mode describes the phase transformation in terms of, respectively, change in the crystal structure and Plasmon energy shift. The orientation relation [001] MgH2 //[-2110] Mg and (-110) MgH2 //(0001) Mg , obtained from the ED study, has been used to propose a model for the movements of magnesium atoms in the structural change to describe the dynamics of the process. The in-situ EELS study has been compared with the existing H-desorption model. The study aims to describe the sorption dynamics of hydrogen in MgH 2 which is a base material for a number of promising hydrogen storage systems. (author)

Study of optical and electronic properties of nickel from reflection electron energy loss spectra

Science.gov (United States)

Xu, H.; Yang, L. H.; Da, B.; Tóth, J.; Tőkési, K.; Ding, Z. J.

2017-09-01

We use the classical Monte Carlo transport model of electrons moving near the surface and inside solids to reproduce the measured reflection electron energy-loss spectroscopy (REELS) spectra. With the combination of the classical transport model and the Markov chain Monte Carlo (MCMC) sampling of oscillator parameters the so-called reverse Monte Carlo (RMC) method was developed, and used to obtain optical constants of Ni in this work. A systematic study of the electronic and optical properties of Ni has been performed in an energy loss range of 0-200 eV from the measured REELS spectra at primary energies of 1000 eV, 2000 eV and 3000 eV. The reliability of our method was tested by comparing our results with the previous data. Moreover, the accuracy of our optical data has been confirmed by applying oscillator strength-sum rule and perfect-screening-sum rule.

Study on tamper-indicating technology in electronic seals system

International Nuclear Information System (INIS)

Xu Xiong; Han Feng; Zuo Guangxia; Zhao Xin; Zhang Quanhu; Di Yuming

2009-01-01

To strengthen our national arms control verification technical storage and deepen electronic seals' research, this paper mainly introduces seals' characteristics, functions and work principle, studies on tamper-indicating technology which is a key technology in electronic seals, designs some hardware circuit such as optical transceiver, temperature detection circuit, move detection circuit, re-prized circuit and so on, also designs a software program which is used for recording the destroying or tampering events' information. Experimental results show that electronic seals system can record the destroying or tampering events' information accurately and quickly, and give corresponding tamper-indication. (authors)

Electron spectroscopy studies in heavy fermions

International Nuclear Information System (INIS)

Arko, A.J.

1986-02-01

Photoemission experiments (whereby an electron absorbs a packet of light energy and is able to escape from the host material due to its increased energy) can measure directly the energy distribution of electrons in various materials. Our measurements on a recently-discovered class of metallic materials called ''heavy fermions'' show that the electrons that actually carry the electric current in these metals exist only within an extremely narrow range of energies. This range, which we will call the bandwidth, is narrower than that found in ordinary metals like copper by at least a factor of 10. Indeed it is surprising that they can carry electric current at all since such narrow energy ranges (or band widths) are characteristic of electrons confined to their host atoms, as in a non-metal, rather than of electrons that are free to wander through a metal. 8 refs

Positron lifetime studies of electron irradiated copper

International Nuclear Information System (INIS)

Hadnagy, T.D.

1976-01-01

Single-crystal copper was irradiated with 4.5-MeV electrons producing simple Frenkel defects as well as a significant concentration of divacancies. Mean positron lifetime characteristics, which are sensitive to the presence of vacancies and multivacancies in copper, was monitored after isochronal anneals between 80 and 800 0 K to determine the relative change of characteristic mean lifetimes and their associated intensities. Also a study of the dependence of the mean positron lifetime on the total electron fluence was made and compared with existing theories relating these lifetimes to vacancy or multivacancy concentrations. Numerical data from curve fitting procedures using a conventional trapping model for defect-induced changes in positron lifetimes indicate that upon irradiation with 4.5-MeV electrons at 80 0 K, about 8 percent of the defects produced are divacancy units. Divacancy units appear to be several times more effective in trapping positrons than are monovacancies. Further, the experimental data suggest that the stage III annealing processes in electron-irradiated copper most probably involve the motion and removal of both monovacancies and divacancies. A conglomerate (multivacancy) unit appears to exist as a stable entity even after annealing procedures are carried out at temperatures slightly above the stage III region. Such a stable unit could serve as a nucleation center for the appearance of voids

Electron microscopy studies of materials used for hydrogen storage

Energy Technology Data Exchange (ETDEWEB)

Andrei, Carmen M.

2004-07-01

Concerns over global warming and air pollution have stimulated the concept of the ''Hydrogen Economy'' and the potential extensive use of hydrogen as an energy carrier. Hydrogen storage in a solid matrix has become one of the promising solutions for vehicular applications. In this study, several transmission electron microscopy (TEM) techniques such as high resolution (HR), electron diffraction, energy dispersive X-ray spectroscopy (EDS), electron energy loss spectroscopy (EELS) and energy-filtered transmission electron microscopy (EFT EM) as well as scanning electron microscopy (SEM) have been used to study the microstructure of materials related to hydrogen storage applications. Some of the results are compared with powder X-ray diffraction (PXD) data. A TbNiAl compound processed by the hydrogenation-disproportionation-desorption-recombination (HDDR) route has been studied using a combination of SEM, TEM and PXD. Information about the variations in the composition and surface topography in both disproportionation and recombination stages is given by the SEM backscattered electrons and secondary electrons images. The crystallites that have undergone the recombination process were found smaller in size. The sodium alanate, NaAIH4 is one of the most promising candidate materials for hydrogen storage. Ti additives are effective at reducing the reaction temperatures and improving the efficiency of the kinetics. The microstructure of NaAlH4 with TiF3 additive has been examined after the initial ball milling and after 15 cycles, using TEM, SEM and EDS. The effect of the additive on particle morphology, grain size and distribution of the phases has been studied. The additive has uneven distribution in the sample after initial ball milling. After 15 cycles, EDS maps show some combination of Ti with the alanate phase. No significant change in grain size of the Na/Al rich particles between the ball milled and 15 cycled sample was observed. The LiAlD4

Comparison of pharmacokinetic profiles of brand-name and generic formulations of citalopram and venlafaxine: a crossover study.

Science.gov (United States)

Chenu, Franck; Batten, Lisa A; Zernig, Gerald; Ladstaetter, Elisabeth; Hébert, Chantal; Blier, Pierre

2009-07-01

Generic drugs are lower-cost versions of patent-expired brand-name medications. Bioequivalence is decreed when the 90% confidence intervals for the ratios of the generic to the reference compound for the area under the curve and maximum plasma concentration (C(max)) fall within a 0.80 to 1.25 range. The aim of the present pilot study was to compare the pharmacokinetic profiles of brand-name and generic formulations of citalopram and extended-release venlafaxine. Effexor XR/Novo-venlafaxine XR 75 mg and Celexa/Gen-citalopram 40 mg were studied in a randomized crossover design. Healthy male volunteers took either Effexor XR or Novo-venlafaxine XR for 4 days, a 4-day washout was allowed, and then participants took the other venlafaxine formulation for 4 days. This was followed by a washout of at least 7 days. The participants then took Celexa or Gen-citalopram for 8 days, a 14-day washout was allowed, and then participants took the other citalopram formulation for 8 days. In each of the study phases, the sequence of treatment (brand-name x generic) was randomly assigned. Plasma levels of drugs were measured at fixed intervals after participants took the drugs and at steady state. The study was conducted from November 2007 through July 2008. Twelve participants completed the venlafaxine study. Nine of the participants, plus 3 new participants, were then enrolled in the citalopram study, to maintain a total of 12. The plasma levels of citalopram were similar after ingestion of the brand-name and generic drugs. After ingestion of venlafaxine, the C(max) values were 36 +/- 6 ng/mL and 52 +/- 8 ng/mL in the brand-name and generic groups, respectively. The ratio of the log-transformed values of C(max) was 150% and, therefore, not within the acceptable 80% to 125% range. The concentration of the active metabolite of venlafaxine (O-desmethyl-venlafaxine [ODV]) was also significantly increased in the generic group (+43% higher in the generic group at 3 h; +48% higher at 5 h; p

Monte Carlo study of electron irradiation effect on YBCO dpa profiles

International Nuclear Information System (INIS)

Pinnera, I.; Cruz, C.; Abreu, Y.; Leyva, A.; Van Espen, P.

2011-01-01

The Monte Carlo assisted Classical Method (MCCM) consists on a calculation procedure for determining the displacements per atom (dpa) distribution in solid materials. This algorithm allows studying the gamma and electron irradiation damage in different materials. It is based on the electrons elastic scattering classic theories and the use of Monte Carlo simulation for the physical processes involved. The present study deals with the Monte Carlo simulation of electron irradiation effects on YBa 2 Cu 3 O 7-x (YBCO) slabs using the MCNPX code system. Displacements per atom distributions are obtained through the MCCM for electron irradiation up to 10 MeV. In-depth dpa profiles for electrons and positrons are obtained and analyzed. Also, for each atomic species in the material, the dpa distributions are calculated. All the results are discussed in the present contribution. (Author)

Secondary electron emission studied by secondary electron energy loss coincidence spectroscopy (SE2ELCS)

International Nuclear Information System (INIS)

Khalid, R.

2013-01-01

Emission of secondary electrons is of importance in many branches of fundamental and applied science. It is widely applied in the electron microscope for the investigation of the structure and electronic state of solid surfaces and particle detection in electron multiplier devices, and generally it is related to the energy dissipation of energetic particles moving inside a solid. The process of secondary electron emission is a complex physical phenomenon, difficult to measure experimentally and treat theoretically with satisfactory accuracy. The secondary electron spectrum measured with single electron spectroscopy does not provide detailed information of the energy loss processes responsible for the emission of secondary electrons. This information can be accessed when two correlated electron pairs are measured in coincidence and the pair consists of a backscattered electron after a given energy loss and a resulting emitted secondary electron. To investigate the mechanisms responsible for the emission of secondary electrons, a reflection (e,2e) coincidence spectrometer named Secondary Electron Electron Energy Loss Coincidence Spectrometer (SE2ELCS) has been developed in the framework of this thesis which allows one to uncover the relation between the features in the spectra which are due to energy losses and true secondary electron emission structures. The correlated electron pairs are measured with a hemispherical mirror analyzer (HMA) and a time of flight analyzer (TOF) by employing a continuous electron beam. An effort has been made to increase the coincidence count rate by increasing the effective solid angle of the TOF analyzer and optimizing the experimental parameters to get optimum energy resolution. Double differential coincidence spectra for a number of materials namely, nearly free electron metals (Al, Si), noble metals (Ag, Au, Cu, W) and highly oriented pyrolytic graphite (HOPG) have been measured using this coincidence spectrometer. The

Study of relativistic electron beams generated by a foilless diode

International Nuclear Information System (INIS)

Jones, M.E.; Thode, L.E.

1979-01-01

Preliminary results of a numerical and analytical study of foilless diodes are presented. The work produced an electron emission algorithm for the particle-in-cell simulation code CCUBE. Diode performance was studied as a function of applied magnetic field strength and simple geometry changes. Annular electron beams with an energy of 5 MeV appear obtainable with densities exceeding 10 14 cm -3 . 8 figures

Ultrafast electron diffraction studies of optically excited thin bismuth films

International Nuclear Information System (INIS)

Rajkovic, Ivan

2008-01-01

This thesis contains work on the design and the realization of an experimental setup capable of providing sub-picosecond electron pulses for ultrafast electron diffraction experiments, and performing the study of ultrafast dynamics in bismuth after optical excitation using this setup. (orig.)

Ultrafast electron diffraction studies of optically excited thin bismuth films

Energy Technology Data Exchange (ETDEWEB)

Rajkovic, Ivan

2008-10-21

This thesis contains work on the design and the realization of an experimental setup capable of providing sub-picosecond electron pulses for ultrafast electron diffraction experiments, and performing the study of ultrafast dynamics in bismuth after optical excitation using this setup. (orig.)

Can Electron-Rich Oxygen (O2-) Withdraw Electrons from Metal Centers? A DFT Study on Oxoanion-Caged Polyoxometalates.

Science.gov (United States)

Takazaki, Aki; Eda, Kazuo; Osakai, Toshiyuki; Nakajima, Takahito

2017-10-12

The answer to the question "Can electron-rich oxygen (O 2- ) withdraw electrons from metal centers?" is seemingly simple, but how the electron population on the M atom behaves when the O-M distance changes is a matter of controversy. A case study has been conducted for Keggin-type polyoxometalate (POM) complexes, and the first-principles electronic structure calculations were carried out not only for real POM species but also for "hypothetical" ones whose heteroatom was replaced with a point charge. From the results of natural population analysis, it was proven that even an electron-rich O 2- , owing to its larger electronegativity as a neutral atom, withdraws electrons when electron redistribution occurs by the change of the bond length. In the case where O 2- coexists with a cation having a large positive charge (e.g., P 5+ (O 2- ) 4 = [PO 4 ] 3- ), the gross electron population (GEP) on the M atom seemingly increases as the O atom comes closer, but this increment in GEP is not due to the role of the O atom but due to a Coulombic effect of the positive charge located on the cation. Furthermore, it was suggested that not GEP but net electron population (NEP) should be responsible for the redox properties.

Dynamic electron arc radiotherapy (DEAR): a feasibility study

International Nuclear Information System (INIS)

Rodrigues, Anna; Yin, Fang-Fang; Wu, Qiuwen

2014-01-01

Compared to other radiation therapy modalities, clinical electron beam therapy has remained practically unchanged for the past few decades even though electron beams with multiple energies are widely available on most linacs. In this paper, we present the concept of dynamic electron arc radiotherapy (DEAR), a new conformal electron therapy technique with synchronized couch motion. DEAR utilizes combination of gantry rotation, couch motion, and dose rate modulation to achieve desirable dose distributions in patient. The electron applicator is kept to minimize scatter and maintain narrow penumbra. The couch motion is synchronized with the gantry rotation to avoid collision between patient and the electron cone. In this study, we investigate the feasibility of DEAR delivery and demonstrate the potential of DEAR to improve dose distributions on simple cylindrical phantoms. DEAR was delivered on Varian's TrueBeam linac in Research Mode. In conjunction with the recorded trajectory log files, mechanical motion accuracies and dose rate modulation precision were analyzed. Experimental and calculated dose distributions were investigated for different energies (6 and 9 MeV) and cut-out sizes (1×10 cm 2  and 3×10 cm 2  for a 15×15 cm 2  applicator). Our findings show that DEAR delivery is feasible and has the potential to deliver radiation dose with high accuracy (root mean square error, or RMSE of <0.1 MU, <0.1° gantry, and <0.1 cm couch positions) and good dose rate precision (1.6 MU min −1 ). Dose homogeneity within ±2% in large and curved targets can be achieved while maintaining penumbra comparable to a standard electron beam on a flat surface. Further, DEAR does not require fabrication of patient-specific shields. These benefits make DEAR a promising technique for conformal radiotherapy of superficial tumors. (paper)

Irradiation-related amorphization and crystallization: In situ transmission electron microscope studies

International Nuclear Information System (INIS)

Allen, C.W.

1994-01-01

Interfacing an ion accelerator to a transmission electron microscope (TEM) allows the analytical functions of TEM imaging and diffraction to be employed during ion-irradiation effects studies. At present there are twelve such installations in Japan, one in France and one in the US. This paper treats several aspects of in situ studies involving electron and ion beam induced and enhanced phase transformations and presents results of several in situ experiments to illustrate the dynamics of this approach in the materials science of irradiation effects. The paper describes the ion- and electron-induced amorphization of CuTi; the ion-irradiation-enhanced transformation of TiCr 2 ; and the ion- and electron-irradiation-enhanced crystallization of CoSi 2

Electron microscope studies

International Nuclear Information System (INIS)

Crewe, A.V.; Kapp, O.H.

1991-01-01

This year our laboratory has continued to make progress in the design of electron-optical systems, in the study of structure-function relationships of large multi-subunit proteins, in the development of new image processing software and in achieving a workable sub-angstrom STEM. We present an algebraic approach to the symmetrical Einzel (unipotential) lens wherein we simplify the analysis by specifying a field shape that meets some preferred set of boundary or other conditions and then calculate the fields. In a second study we generalize this approach to study of three element electrostatic lenses of which the symmetrical Einzel lens is a particular form. The purpose is to develop a method for assisting in the design of a lens for a particular purpose. In our biological work we study a stable and functional dodecameric complex of globin chains from the hemoglobin of Lumbricus terrestris. This is a complex lacking the ''linker'' subunit first imaged in this lab and required for maintenance of the native structure. In addition, we do a complete work-up on the hemoglobin of the marine polychaete Eudistylia vancouverii demonstrating the presence of a hierarchy of globin complexes. We demonstrate stable field-emission in the sub-angstrom STEM and the preliminary alignment of the beam. We continue our exploration of a algorithms for alignment of sequences of protein and DNA. Our computer facilities now include four second generation RISC workstations and we continue to take increasing advantage of the floating-point and graphical performance of these devices

A study of core electron binding energies in technetium-99m complexes by internal conversion electron spectroscopy

International Nuclear Information System (INIS)

Burke, J.F.; Archer, C.M.; Wei Chiu, K.; Latham, I.A.; Egdell, R.G.

1991-01-01

Core electron binding energies in a series of 99m Tc complexes have been studied by internal conversion electron spectroscopy (ICES) in a conventional x-ray photoelectron spectrometer. In both 3d and 3p regions, a chemical shift of about 1 eV is observed per unit increase in oxidation state. The role of ICES in characterizing radiopharmaceutical agents is illustrated with studies of some novel 99m Tc-phosphine complexes that have been developed for myocardial perfusion imaging. (author)

Study of Compton broadening due to electron-photon scattering

Directory of Open Access Journals (Sweden)

Srinivasa Rao M.

2010-01-01

Full Text Available We have investigated the effects of Compton broadening due to electron-photon scattering in hot stellar atmospheres. A purely electron-photon scattering media is assumed to have plane parallel geometry with an input radia­tion field localized on one side of the slab. The method is based on the discrete space theory of radiative transfer for the intensity of emitted radiation. The solution is developed to study the importance of scattering of radiation by free electrons in high temperature stellar atmospheres which produces a brodening and shift in spectral lines because of the Compton effect and the Doppler effect arising from mass and thermal motions of scattering electrons. It is noticed that the Comptonized spectrum depends on three parameters: the optical depth of the medium, the temperature of the thermal electrons and the viewing angle. We also showed that the Compton effect produces red shift and asymmetry in the line. These two effects increase as the optical depth increases. It is also noticed that the emergent specific intensities become completely asymmetric for higher optical depths.

Study of Compton Broadening Due to Electron-Photon Scattering

Directory of Open Access Journals (Sweden)

Srinivasa Rao, M.

2010-06-01

Full Text Available We have investigated the effects of Compton broadening due to electron-photon scattering in hot stellar atmospheres. A purely electron-photon scattering media is assumed to have plane parallel geometry with an input radiation field localized on one side of the slab. The method is based on the discrete space theory of radiative transfer for the intensity of emitted radiation.The solution is developed to study the importance of scattering of radiation by free electrons in high temperature stellar atmospheres which produces a brodening and shift in spectral lines because of the Compton effect and the Doppler effect arising from mass and thermal motions of scattering electrons.It is noticed that the Comptonized spectrum depends on three parameters: the optical depth of the medium, the temperature of the thermal electrons and the viewing angle.We also showed that the Compton effect produces red shift and asymmetry in the line. These two effects increase as the optical depth increases. It is also noticed that the emergent specific intensities become completely asymmetric for higher optical depths.

Dosimetry study for electron beam irradiation in radiation processing

International Nuclear Information System (INIS)

Sunaga, Hiromi; Haruyama, Yasuyuki; Takizawa, Haruki; Kojima, Takuji; Yotsumoto, Keiichi

1995-01-01

For certain critical applications such as medical device sterilization and food irradiation, accurate calibration of electron energy and absorbed dose is required to assure the quality of irradiated products. To meet this requirement, TRCRE, JAERI has carried out research and development on high dose radiation dosimetry for electron beams in the energy range used in radiation processing (0.15 - 3.0 MeV). JAERI has developed a simultaneous electron beam energy and dosimeter calibration system that consist of a total absorption calorimeter, an electron current density meter, and a stacked thin-film dosimeter set. For low energy electrons, where it is important to measure the depth-dose profile in materials with high depth resolution, we studied the feasibility of a method using Gafchromic film dosimeters. This film, which has an 8-μm thick sensitive layer, is combined with a stepped array of absorber films of the same thickness to produce a high-resolution depth-dose profile on the Gafchromic film. The depth-dose profile obtained in this manner has about five times greater resolution than conventional radiochromic film dosimetry. (author)

Electron spectroscopy studies of argon K-shell excitation and vacancy cascades

International Nuclear Information System (INIS)

Southworth, S.H.; MacDonald, M.A.; LeBrun, T.; Azuma, Y.; Cooper, J.W.

1995-01-01

Electron spectroscopy combined with tunable synchrotron radiation has been used for studies of Ar K-shell excitation and vacancy decay processes. In addition, electrons and fluorescent X-rays have been recorded in coincidence to select subsets of the ejected electron spectra. Examples are presented for Ar 1s photoelectrons and KLL and LMM Auger spectra

The electronic structure of VO in its ground and electronically excited states: A combined matrix isolation and quantum chemical (MRCI) study

International Nuclear Information System (INIS)

Hübner, Olaf; Hornung, Julius; Himmel, Hans-Jörg

2015-01-01

The electronic ground and excited states of the vanadium monoxide (VO) molecule were studied in detail. Electronic absorption spectra for the molecule isolated in Ne matrices complement the previous gas-phase spectra. A thorough quantum chemical (multi-reference configuration interaction) study essentially confirms the assignment and characterization of the electronic excitations observed for VO in the gas-phase and in Ne matrices and allows the clarification of open issues. It provides a complete overview over the electronically excited states up to about 3 eV of this archetypical compound

New pbysical methods used in the study of composition, electronic properties and surface phenomena of solid substances. I. Electronic spectroscopies

International Nuclear Information System (INIS)

Toderean, A; Ilonca, Gh.

1981-01-01

The discovery of different kinds of interactions between solids and fotonic, respectively electronic and ionic beams, leads to the development of many new, very sensitive, physical methods for the study of solids. This monograph tries to present some of these methods, useful in compositional analysis, in the study of electronic properties and of the surface processes of solid substances. This is done from the point of view both of physical phenomena underlying them and of the information obtainable with such methods. But the whole monograph is limited only to the methods based on the electronic properties of the elements existing in the solid probes studied and this paper presents only those of them in which the detected beam is an electronic one, like: ELS, DAPS, ILS, AES, AEAPS, INS, TSS, XPS and UPS. (authors)

NATO Advanced Study Institute on Superconducting Electronics

CERN Document Server

Nisenhoff, Martin; Superconducting Electronics

1989-01-01

The genesis of the NATO Advanced Study Institute (ASI) upon which this volume is based, occurred during the summer of 1986 when we came to the realization that there had been significant progress during the early 1980's in the field of superconducting electronics and in applications of this technology. Despite this progress, there was a perception among many engineers and scientists that, with the possible exception of a limited number of esoteric fundamental studies and applications (e.g., the Josephson voltage standard or the SQUID magnetometer), there was no significant future for electronic systems incorporating superconducting elements. One of the major reasons for this perception was the aversion to handling liquid helium or including a closed-cycle helium liquefier. In addition, many critics felt that IBM's cancellation of its superconducting computer project in 1983 was "proof" that superconductors could not possibly compete with semiconductors in high-speed signal processing. From our persp...

Electron holography study on the microstructure of magnetic tunnelling junctions

International Nuclear Information System (INIS)

Xu, Q.Y.; Wang, Y.G.; You, B.; Du, J.; Hu, A.; Zhang, Z.

2004-01-01

Electron holography was applied to study the microstructure evolution of magnetic tunnelling junctions (MTJs) CoFe/AlO x /Co annealed at different temperatures. A mean inner potential barrier was observed in the as-deposited MTJ sample, while it was changed to a potential well after a 200 deg. C or a 400 deg. C annealing. It is suggested that the oxygen atoms were redistributed during the annealing, which left metallic atoms acting as acceptors to confine the electrons, leading to the decrease of the potential of the AlO x barrier layer. The results suggest that the electron holography may be a useful tool for the study of the microstructure of amorphous materials

21 CFR 320.38 - Retention of bioavailability samples.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Retention of bioavailability samples. 320.38... (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.38 Retention of bioavailability samples...

Optimization of power output and study of electron beam energy spread in a Free Electron Laser oscillator

International Nuclear Information System (INIS)

Abramovich, A.; Pinhasi, Y.; Yahalom, A.; Bar-Lev, D.; Efimov, S.; Gover, A.

2001-01-01

Design of a multi-stage depressed collector for efficient operation of a Free Electron Laser (FEL) oscillator requires knowledge of the electron beam energy distribution. This knowledge is necessary to determine the voltages of the depressed collector electrodes that optimize the collection efficiency and overall energy conversion efficiency of the FEL. The energy spread in the electron beam is due to interaction in the wiggler region, as electrons enter the interaction region at different phases relative to the EM wave. This interaction can be simulated well by a three-dimensional simulation code such as FEL3D. The main adjustable parameters that determine the electron beam energy spread after interaction are the e-beam current, the initial beam energy, and the quality factor of the resonator out-coupling coefficient. Using FEL3D, we study the influence of these parameters on the available radiation power and on the electron beam energy distribution at the undulator exit. Simulations performed for I=1.5 A, E=1.4 MeV, L=20% (Internal loss factor) showed that the highest radiated output power and smallest energy spread are attained for an output coupler transmission coefficient T m congruent with 30%

Study of γ-irradiated lithographic polymers by electron spin resonance and electron nuclear double resonance

International Nuclear Information System (INIS)

Schlick, S.; Kevan, L.

1982-01-01

The room temperature gamma irradiation degradation of the lithographic polymers, poly(methylmethacrylate) (PMMA), poly(methyl-α-chloroacrylate) (PMCA), poly(methyl-α-fluoroacrylate) (PMFA), and poly(methylacrylonitrile) (PMCN), have been studied by electron spin resonance and electron nuclear double resonance (ENDOR) to assess their molecular degradation processes of relevance to electron beam lithography. Two classes of radicals are found, chain radicals and chain scission radicals. PMMA and PMCA mainly form chain scission radicals consistent with degradation while for PMCN the resolution is poorer, and this is only probable. PMFA forms mainly chain radicals consistent with predominant crosslinking. The total radical yield is greatest in PMCA and PMCN. ENDOR is used to assess the compactness of the radiation degradation region for PMMA and PMCA and hence the potential resolution of the resist; this appears to be about the same for these methacrylate polymers

An Empirical Study of Logistics Organization, Electronic Linkage, and Performance

Science.gov (United States)

1993-01-01

Anvari, M., "Electronic Data Interchange and Inventories," International Journal of Production Economics , 26, 1-3 (1992), 135-143. Baker, R. H., EDI: What...Electronic Data Interchange -- A Study of Norwegian Freight Forwarders Using EDI," International Journal of Production Economics , 24 (1991), 91-101. Henry, G

Electron-beam generated porous dextran gels: experimental and quantum chemical studies.

Science.gov (United States)

Naumov, Sergej; Knolle, Wolfgang; Becher, Jana; Schnabelrauch, Matthias; Reichelt, Senta

2014-06-01

The aim of this work was to investigate the reaction mechanism of electron-beam generated macroporous dextran cryogels by quantum chemical calculation and electron paramagnetic resonance measurements. Electron-beam radiation was used to initiate the cross-linking reaction of methacrylated dextran in semifrozen aqueous solutions. The pore morphology of the resulting cryogels was visualized by scanning electron microscopy. Quantum chemical calculations and electron paramagnetic resonance studies provided information on the most probable reaction pathway and the chain growth radicals. The most probable reaction pathway was a ring opening reaction and the addition of a C-atom to the double-bond of the methacrylated dextran molecule. First detailed quantum chemical calculation on the reaction mechanism of electron-beam initiated cross-linking reaction of methacrylated dextran are presented.

Ab initio study of hot electrons in GaAs

OpenAIRE

Bernardi, Marco; Vigil-Fowler, Derek; Ong, Chin Shen; Neaton, Jeffrey B.; Louie, Steven G.

2015-01-01

Hot carrier dynamics critically impacts the performance of electronic, optoelectronic, photovoltaic, and plasmonic devices. Hot carriers lose energy over nanometer lengths and picosecond timescales and thus are challenging to study experimentally, whereas calculations of hot carrier dynamics are cumbersome and dominated by empirical approaches. In this work, we present ab initio calculations of hot electrons in gallium arsenide (GaAs) using density functional theory and many-body perturbation...

Experimental study of parametric dependence of electron-scale turbulence in a spherical tokamak

Energy Technology Data Exchange (ETDEWEB)

Ren, Y.; Guttenfelder, W.; Kaye, S. M.; Mazzucato, E.; Bell, R. E.; Diallo, A.; LeBlanc, B. P. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543 (United States); Domier, C. W.; Lee, K. C. [University of California at Davis, Davis, California 95616 (United States); Smith, D. R. [University of Wisconsin-Madison, Madison, Wisconsin 53706 (United States); Yuh, H. [Nova Photonics, Inc., Princeton, New Jersey 08540 (United States)

2012-05-15

Electron-scale turbulence is predicted to drive anomalous electron thermal transport. However, experimental study of its relation with transport is still in its early stage. On the National Spherical Tokamak Experiment (NSTX), electron-scale density fluctuations are studied with a novel tangential microwave scattering system with high radial resolution of {+-}2 cm. Here, we report a study of parametric dependence of electron-scale turbulence in NSTX H-mode plasmas. The dependence on density gradient is studied through the observation of a large density gradient variation in the core induced by an edge localized mode (ELM) event, where we found the first clear experimental evidence of density gradient stabilization of electron-gyro scale turbulence in a fusion plasma. This observation, coupled with linear gyro-kinetic calculations, leads to the identification of the observed instability as toroidal electron temperature gradient (ETG) modes. It is observed that longer wavelength ETG modes, k{sub Up-Tack }{rho}{sub s} Less-Than-Or-Equivalent-To 10 ({rho}{sub s} is the ion gyroradius at electron temperature and k{sub Up-Tack} is the wavenumber perpendicular to local equilibrium magnetic field), are most stabilized by density gradient, and the stabilization is accompanied by about a factor of two decrease in electron thermal diffusivity. Comparisons with nonlinear ETG gyrokinetic simulations show ETG turbulence may be able to explain the experimental electron heat flux observed before the ELM event. The collisionality dependence of electron-scale turbulence is also studied by systematically varying plasma current and toroidal field, so that electron gyroradius ({rho}{sub e}), electron beta ({beta}{sub e}), and safety factor (q{sub 95}) are kept approximately constant. More than a factor of two change in electron collisionality, {nu}{sub e}{sup *}, was achieved, and we found that the spectral power of electron-scale turbulence appears to increase as {nu}{sub e}{sup *} is

Study of fast electrons from hard-X radiation; Etude des electrons rapides a partir du rayonnement X-dur

Energy Technology Data Exchange (ETDEWEB)

Arslanbekov, R.

1995-12-19

The goal of this thesis is the study of fast electron dynamics by means of the hard X-ray diagnosis installed in TORE SUPRA and numerical simulations. Fast electrons are generated in the plasma in the presence of the injected lower hybrid (LH) waves. Two aspects are studied in detail: the lower hybrid wave propagation and absorption in a periodically perturbed media and 2-D Fokker-Planck modelling of the fast electron dynamics in the presence of the LH power. Ripple effects on lower hybrid wave propagation and absorption are investigated using the ray tracing technique. A cylindrical equilibrium is first studied and a strong modification of the ray dynamics is predicted. Calculations are carried out in a real toroidal geometry corresponding to TORE SUPRA. It is shown that the lack of toroidal axisymmetry of the magnetic field may result in a modification of the ray evolution even if the global ray evolution is governed by the larger poloidal inhomogeneity. Simulation of LH experiments are performed for TORE SUPRA tokamak which has a large magnetic ripple (7% at the plasma edge). By considering ripple perturbation in LH current drive simulations, a better agreement is found with experimental results, in particular with the hard-X spectra and the current density profiles. In the second part of the thesis, a 2-D modeling of the fast electron dynamics in the velocity phase space is considered, based on the 2-D relativistic electron Fokker-Planck equation. Electron distribution functions obtained are used to calculate non-thermal Bremsstrahlung emission for different TORE SUPRA shots in a wide range of experimental conditions. (J.S.). 168 refs., 93 figs., 1 tab., 3 appendix.

Neo-Institutional Approach to the Study of Electronic Government

Directory of Open Access Journals (Sweden)

Yan I. Vaslavskiy

2016-01-01

Full Text Available The article is devoted to the neo-institutional approach as a methodological basis in the study of electronic government. In this article substantiates the choice of neo-institutional approach to the study of the processes of implementation of information and communication technologies in the activity of state institutions, analyzes the differences of neoinstitutionalism from traditional institutional approach, considers the features of the different directions of neo-institutionalism, namely sociological, historical and rational choice theory. Attention is paid to the reasons for the renewed interest in political institutions in political science. The article emphasizes the importance of considering the electronic government as an institution, and the conditions for its implementation in the Russian political system as the institutional environment. The authors pay special attention to the variety of sociological neo-institutionalism, used, in addition to political science in sociology of organizations. The article substantiates the value of using sociological institutionalism to explore the electronic government based on a comparative analysis of e-government projects in Russia and abroad and explores its heuristic capabilities. It examines the impact of the system of norms and values of the institutional environment on the processes of formation and development of electronic government in Russia. The research capacity of this theory is due to the fact that it allows us to trace the reasons for copying and replication of inefficient practices and organizational and management schemes, to identify the factors impeding innovation use by the state of electronic interaction technologies. It is emphasized that the use of the theory of institutional isomorphism is useful in the sphere of implementation of electronic technologies, in which a key role play pluralism, horizontal managerial communication, inter-agency coordination.

Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

Science.gov (United States)

Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

2017-02-01

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

Studies of electron correlation in the photoionization process

Energy Technology Data Exchange (ETDEWEB)

Rosenberg, Richard Allen [Univ. of California, Berkeley, CA (United States)

1979-03-01

Electron correlation is a result of the interaction of two or more electrons confined in a region of space, and may conveniently be treated under the formalism of configuration interaction (CI). Photoionization provides a rather direct experimental method for studying configuration interaction. The types of CI involved in the photoionization process can be divided into three categories: initial state configuration interaction (ISCI), final ionic state configuration interaction (FISCI), and continuum state configuration interaction (CSCI). This thesis deals with experimental studies which reveal how the various types of CI may become manifested in photoionization. The experimental methods utilized in this work are photoelectron spectroscopy (PES), electron impact spectroscopy (EIS), and time-resolved fluorescence spectroscopy. The EIS was carried out following the discovery that the UV lamp on a Perkin-Elmer photoelectron spectrometer could be utilized as a source of low energy electrons. The time-resolved fluorescence work utilized both the tunability and the time structure of the radiation available at the Stanford Synchrotron Radiation Laboratory (SSRL). A commercial photoelectron spectrometer equipped with a conventional UV lamp (Hei, Nei) was employed for some of the PES studies, and a novel time-of-flight photoelectron spectrometer was developed for the PES work performed using synchrotron radiation. The PES of Ba, Sm, Eu, and Yb was studied using both Hei (22.22 eV) and Nei (16.85 eV) radiation. Satellite structure observed in these spectra using Nei (and for Yb, Hei also) radiation could be satisfactorily explained by ISCI alone. The Hei spectra of Sm, Eu, and, in particular, Ba showed dramatic changes in the satellite population which could only be explained by a new mechanism, autoionization, which is a special form of CSCI. The detailed nature of this mechanism was explored in Ba using synchrotron radiation. It was found that the autoionizing level decays

Experimental study on generation of large area uniform electron beam

International Nuclear Information System (INIS)

Tang Ying; Yi Aiping; Liu Jingru; Qian Hang; Huang Xin; Yu Li; Su Jiancang; Ding Zhenjie; Ding Yongzhong; Yu Jianguo

2007-01-01

In the experiment of gas laser pumped by electron beam, large area uniform electron beam is important to generate high efficiency laser output. The experimental study on generation of large area uniform electron beam with SPG-200 pulsed power generator is introduced. SPG-200 is an all-solid-state components pulsed power generator based on SOS, and its open voltage is more than 350 kV. The cathode have the area of 24 mm x 294 mm, and the anode-cathode(A-C)gap spacing is adjustable from 0 to 49 mm. The electron beam of cathode emission is transported to the laser chamber through the diode pressure foil, which sepa-rates the vacuum chamber from the laser chamber. Velvet and graphite cathodes are studied, each generates large area electron beam. The diode parameters are presented, and the uniformity of e-beam is diagnosed. The experimental results show that the diode voltage of the graphite cathode is 240-280 kV, and the diode current is 0.7-1.8 kA. The diode voltage of the velvet cathode is 200-250 kV, and the diode current is 1.5-1.7 kA. The uniformity of the velvet cathode emission is better than that of the graphite cathode. (authors)

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

Science.gov (United States)

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

Electronic journals and scholarly communication: a citation and reference study

Directory of Open Access Journals (Sweden)

Stephen P. Harter

1996-01-01

Full Text Available The journal is fundamental to formal scholarly communication. This research reports highlights and preliminary findings from an empirical study of scholarly electronic journals. The purpose of the research is to assess the impact of electronic journals (e-journals on scholarly communication, by measuring the extent to which they are being cited in the literature, both print and electronic. The intent is to provide a snapshot of the impact e-journals were having on scholarly communication at a given point in time, roughly the end of 1995. This study provides one measure of that impact, specifically on the formal, as opposed to informal, communication process. The study also examines the forms in which scholars cite e-journals, the accuracy and completeness of citations to e-journals, and practical difficulties faced by scholars and researchers who wish to retrieve e-journals through the networks.

Study and realization of an electron linear accelerator. Dynamics of accelerated electrons; Etude et realisation d'un accelerateur lineaire d'electrons. Dynamique des electrons acceleres

Energy Technology Data Exchange (ETDEWEB)

Bernard, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1967-04-01

The theoretical characteristics of the electron linear accelerator are: 30 MeV for the energy W{sub S} and 250 mA for the peak current I{sub c}. The main utilization is the intense production of fast neutrons by the reactions ({gamma},n) and ({gamma},f) induced in a target of natural uranium by the accelerated electrons. In the first part of the thesis, relative to the study and the realization of the accelerator, a new equation of dispersion is established analytically when the guide is loaded with round-edged irises. The relation is compared with the equation established by CHU and Hansen, WALKINSHAW, KVASIL in the case of a guide loaded with flat-edged irises. The experimental and theoretical curves of dispersion are compared. The accuracy of every relation of dispersion is estimated. The second part of the thesis is relative to the theoretical study of the electrons dynamics in the guide; it allows the derivation of the parameters of the beam: dispersion of phase, energy, dispersion of energy and the relation W{sub S} = f (I{sub c}). The results relative to the first experiments are given and compared with the theoretical expectations. (author) [French] Les caracteristiques nominales theoriques de l'accelerateur lineaire d'electrons sont: 30 MeV pour l'energie W{sub S} et 250 mA pour le courant de crete I{sub c}. L'utilisation principale envisagee est la production de neutrons rapides par les reactions ({gamma},n) et ({gamma},f) induites dans une cible d'uranium naturel par les electrons acceleres. Dans la premiere partie de la these relative a l'elude et a la realisation de l'accelerateur, une nouvelle equation de dispersion (ou equation aux frequences) est etablie analytiquement pour un guide charge par des iris a bord rond. Cette relation est comparee a celles etablies par CHU et HANSEN, WALKINSHAW, KVASIL dans le cas du guide charge par des iris a bord plat. On compare les courbes de dispersion theoriques et experimentales et on evalue la precision de

Design studies on high current and grid control electron gun

International Nuclear Information System (INIS)

Wang Jinnan; Lu Kun; Chi Yunlong; Zhou Zusheng

2011-01-01

Electron gun, the source of electrons, is a kind of ultrahigh vacuum device and plays an important role in different kind of accelerators. With the irradiation accelerator demands, describes the design studies on beam optics optimization. The simulation result shows that the beam current is above 5 A with cathode voltage of 80 kV and beam emittance, gun electric field and beam waist radius meet the accelerator needs. The electron gun manufactured and installed in the test stand, the conditioning and test will be done in the near future. (authors)

78 FR 5816 - Electronic Study Data Submission; Data Standard Support End Date

Science.gov (United States)

2013-01-28

...] Electronic Study Data Submission; Data Standard Support End Date AGENCY: Food and Drug Administration, HHS... Safety and Innovation Act (FDASIA) (Public Law 112- 144), requires electronic submission of drug and... comment, will specify the format required for such electronic submissions. The action announced in this...

The role of low-energy electrons in focused electron beam induced deposition: four case studies of representative precursors

Directory of Open Access Journals (Sweden)

Rachel M. Thorman

2015-09-01

Full Text Available Focused electron beam induced deposition (FEBID is a single-step, direct-write nanofabrication technique capable of writing three-dimensional metal-containing nanoscale structures on surfaces using electron-induced reactions of organometallic precursors. Currently FEBID is, however, limited in resolution due to deposition outside the area of the primary electron beam and in metal purity due to incomplete precursor decomposition. Both limitations are likely in part caused by reactions of precursor molecules with low-energy (3, Pt(PF34, Co(CO3NO, and W(CO6. Through these case studies, it is evident that this combination of studies can provide valuable insight into potential mechanisms governing deposit formation in FEBID. Although further experiments and new approaches are needed, these studies are an important stepping-stone toward better understanding the fundamental physics behind the deposition process and establishing design criteria for optimized FEBID precursors.

Electron-electron luminosity in the Next Linear Collider -- a preliminary study

International Nuclear Information System (INIS)

Zimmermann, F.; Thompson, K.A.; Helm, R.H.

1997-11-01

In this paper, the authors discuss some operational aspects of electron-electron collisions at the Next Linear Collider (NLC) and estimate the luminosity attainable in such a machine. They also consider the use of two future technologies which could simplify the operation and improve the luminosity in an e - e - collider: polarized rf guns and plasma lenses

Pharmacokinetic equivalence study of two formulations of the anticonvulsant pregabalin

Directory of Open Access Journals (Sweden)

Tjandrawinata RR

2015-04-01

Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Ratih Sofia Ika Putri,2 Vincent Angga Gunawan,2 Fenny Ong,1 Liana W Susanto,1 Dwi Nofiarny11Dexa Laboratories of Biomolecular Sciences, Cikarang, West Java, Indonesia; 2PT Equilab International Bioavailability and Bioequivalence Laboratory, Jakarta, IndonesiaPurpose: The present study was conducted to evaluate whether the bioavailability of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to the reference formulation.Methods: This was a randomized, open-label, two-period, two-sequence, and crossover study under fasting condition, with a 1-week washout period. Plasma concentrations of pregabalin from 20 subjects were determined by using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS detection method. Pharmacokinetic parameters assessed in this study were: area under the plasma concentration–time curve from time zero to last observed quantifiable concentration (AUC0–t, area under the plasma concentration–time curve from time zero to infinity (AUC0–∞, maximum plasma concentration (Cmax, time to maximum plasma concentration (tmax, and terminal half-life (t1/2. The 90% confidence intervals (CIs for the geometric mean ratios of test formulation/reference formulation were calculated for the AUC and Cmax parameters; while tmax difference was analyzed nonparametrically on the original data using the Wilcoxon matched-pairs test, and t1/2 difference was analyzed using Student's paired t-test.Results: The mean (standard deviation [SD] AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the test formulation were 27,845.86 (4,508.27 ng·h/mL, 28,311.70 (4,790.55 ng·h/mL, 3,999.71 (801.52 ng/mL, and 5.66 (1.20 hours, respectively; while the mean (SD AUC0–t, AUC0–∞, Cmax, and t1/2 of pregabalin from the reference formulation were 27,398.12 (4,266.28 ng·h/mL, 27,904.24 (4,507.31 ng·h/mL, 3,849.50 (814.50 ng/mL, and 5.87 (1.25 hours, respectively

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

Directory of Open Access Journals (Sweden)

Rong Zheng

2012-02-01

Full Text Available A fast, simple and sensitive high performance liquid chromatographic (HPLC method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline in human plasma. One-step liquid–liquid extraction (LLE with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS. Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm using acetonitrile–ammonium acetate (0.1 mol/L (15/85, v/v as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288–73.2 ng/mL with a lower limit of quantitation (LLOQ of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers. Keywords: Nicergoline, 10α-methoxy-6-methylergoline-8β-methanol (MDL, HPLC, Plasma-drug concentration, Bioequivalence study

Study of warm dense plasma electronic dynamics by optical interferometry

International Nuclear Information System (INIS)

Deneuville, F.

2013-01-01

The Warm Dense Matter (WDM) regime is characterised by a density close to the solid density and an electron temperature close to the Fermi temperature. In this work, the nonequilibrium Warm Dense Matter is studied during the solid to liquid phase transition induced by an ultra short laser interacting with a solid. A 30 femtosecond time resolution pump-probe experiment (FDI) is set up, yielding to the measurement of the heated sample complex reflectivity for both S and P polarisation. We have determined a criterion based on the measured reflectivities, which permits to control the interface shape of the probed matter. For pump laser fluences around 1 J/cm 2 , the hydrodynamics of the heated matter is studied and experimental results are compared to the two-temperatures code ESTHER. Furthermore, the evolution of the dielectric function at 800 nm and 400 nm is inferred from our measurements on a sub-picosecond time-scale. Within the Drude-Lorentz model for the conduction electrons, the dielectric function yields information such as ionisation state, electronic temperature and electron collision frequency. (author) [fr

Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting.

Science.gov (United States)

Markoula, Sofia; Chatzistefanidis, Dimitrios; Gatzonis, Stylianos; Siatouni, Anna; Siarava, Eleftheria; Verentzioti, Anastasia; Kyritsis, Athanassios P; Patsalos, Philip N

2017-05-01

The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. Patients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Study of total ionization dose effects in electronic devices

International Nuclear Information System (INIS)

Nidhin, T.S.; Bhattacharyya, Anindya; Gour, Aditya; Behera, R.P.; Jayanthi, T.

2018-01-01

Radiation effects in electronic devices are a major challenge in the dependable application developments of nuclear power plant instrumentation and control systems. The main radiation effects are total ionization dose (TID) effects, displacement damage dose (DDD) effects and single event effects (SEE). In this study, we are concentrating on TID effects in electronic devices. The focus of the study is mainly on SRAM based field programmable gate arrays (FPGA) along with that the devices of our interest are voltage regulators, flash memory and optocoupler. The experiments are conducted by exposing the devices to gamma radiation in power off condition and the degradation in the performances are analysed

Temperature-dependent surface structure, composition, and electronic properties of the clean SrTiO3(111) crystal face: Low-energy-electron diffraction, Auger-electron spectroscopy, electron energy loss, and ultraviolet-photoelectron spectroscopy studies

International Nuclear Information System (INIS)

Lo, W.J.; Somorjai, G.A.

1978-01-01

Low-energy-electron diffraction, Auger-electron spectroscopy, electron-energy-loss, and ultraviolet-photoelectron spectroscopies were used to study the structure, composition, and electron energy distribution of a clean single-crystal (111) face of strontium titanate (perovskite). The dependence of the surface chemical composition on the temperature has been observed along with corresponding changes in the surface electronic properties. High-temperature Ar-ion bombardment causes an irreversible change in the surface structure, stoichiometry, and electron energy distribution. In contrast to the TiO 2 surface, there are always significant concentrations of Ti 3+ in an annealed ordered SrTiO 3 (111) surface. This stable active Ti 3+ monolayer on top of a substrate with large surface dipole potential makes SrTiO 3 superior to TiO 2 when used as a photoanode in the photoelectrochemical cell

ANALYTICAL REVIEW OF ELECTRONIC RESOURCES FOR THE STUDY OF LATIN

Directory of Open Access Journals (Sweden)

Olena Yu. Balalaieva

2014-04-01

Full Text Available The article investigates the current state of development of e-learning content in the Latin language. It is noted that the introduction of ICT in the educational space has expanded the possibility of studying Latin, opened access to digital libraries resources, made it possible to use scientific and educational potential and teaching Latin best practices of world's leading universities. A review of foreign and Ukrainian information resources and electronic editions for the study of Latin is given. Much attention was paid to the didactic potential of local and online multimedia courses of Latin, electronic textbooks, workbooks of interactive tests and exercises, various dictionaries and software translators, databases and digital libraries. Based on analysis of the world market of educational services and products the main trends in the development of information resources and electronic books are examined. It was found that multimedia courses with interactive exercises or workbooks with interactive tests, online dictionaries and translators are the most widely represented and demanded. The noticeable lagging of Ukrainian education and computer linguistics in quantitative and qualitative measures in this industry is established. The obvious drawback of existing Ukrainian resources and electronic editions for the study of Latin is their noninteractive nature. The prospects of e-learning content in Latin in Ukraine are outlined.

Electron-electron coincidence spectroscopies at surfaces

International Nuclear Information System (INIS)

Stefani, G.; Iacobucci, S.; Ruocco, A.; Gotter, R.

2002-01-01

In the past 20 years, a steadily increasing number of electron-electron coincidence experiments on atoms and molecules have contributed to a deeper understanding of electron-electron correlation effects. In more recent years this technique has been extended to the study of solid surfaces. This class of one photon IN two electrons OUT experiments will be discussed with an emphasis on grazing incidence geometry, that is expected to be particularly suited for studying surfaces. The crucial question of which is the dominant mechanism that leads to ejection of pairs of electron from the surface will be addressed. It will be shown that, depending on the kinematics chosen, the correlated behaviour of the pairs of electrons detected might be singled out from independent particle one

Study of heliumlike neon using an electron beam ion trap

International Nuclear Information System (INIS)

Wargelin, B.J.; Kahn, S.M.; Beiersdorfer, P.

1992-01-01

The 2-to-1 spectra of several astrophysically abundant He-like ions are being studied using the Electron Beam Ion Trap (EBIT) at Lawrence Livermore National Laboratory. Spectra are recorded for a broad range of plasma parameters, including electron density, energy, and ionization balance. We describe the experimental equipment and procedure and present some typical data

Test beam studies for the atlas tile calorimeter readout electronics

CERN Document Server

Rodriguez Perez, Andrea; The ATLAS collaboration

2018-01-01

The Large Hadron Collider (LHC) Phase II upgrade aims to increase the accelerator luminosity by a factor of 5-10. Due to the expected higher radiation levels and the aging of the current electronics, a new readout system for the Tile hadronic calorimeter (TileCal) of the ATLAS experiment is needed. A prototype of the upgrade TileCal electronics has been tested using the beam from the Super Proton Synchrotron (SPS) accelerator at CERN. Data were collected with beams of muons, electrons and hadrons at various incident energies and impact angles. The muon data allow to study the response dependence on the incident point and angle in a cell and inter-calibration of the response between cells. The electron data are used to determine the linearity of the electron energy measurement. The hadron data allow to determined the calorimeter response to pions, kaons and protons and tune the calorimeter simulation to that data. The results of the ongoing data analyses are discussed in the presentation.

Electron transport and nonlinear optical properties of substituted aryldimesityl boranes: a DFT study.

Directory of Open Access Journals (Sweden)

Altaf Hussain Pandith

Full Text Available A comprehensive theoretical study was carried out on a series of aryldimesityl borane (DMB derivatives using Density Functional theory. Optimized geometries and electronic parameters like electron affinity, reorganization energy, frontiers molecular contours, polarizability and hyperpolarizability have been calculated by employing B3PW91/6-311++G (d, p level of theory. Our results show that the Hammett function and geometrical parameters correlates well with the reorganization energies and hyperpolarizability for the series of DMB derivatives studied in this work. The orbital energy study reveals that the electron releasing substituents increase the LUMO energies and electron withdrawing substituents decrease the LUMO energies, reflecting the electron transport character of aryldimesityl borane derivatives. From frontier molecular orbitals diagram it is evident that mesityl rings act as the donor, while the phenylene and Boron atom appear as acceptors in these systems. The calculated hyperpolarizability of secondary amine derivative of DMB is 40 times higher than DMB (1. The electronic excitation contributions to the hyperpolarizability studied by using TDDFT calculation shows that hyperpolarizability correlates well with dipole moment in ground and excited state and excitation energy in terms of the two-level model. Thus the results of these calculations can be helpful in designing the DMB derivatives for efficient electron transport and nonlinear optical material by appropriate substitution with electron releasing or withdrawing substituents on phenyl ring of DMB system.

Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

Science.gov (United States)

Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

2004-07-01

The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

Sounding rocket study of auroral electron precipitation

International Nuclear Information System (INIS)

McFadden, J.P.

1985-01-01

Measurement of energetic electrons in the auroral zone have proved to be one of the most useful tools in investigating the phenomena of auroral arc formation. This dissertation presents a detailed analysis of the electron data from two sounding rocket campaigns and interprets the measurements in terms of existing auroral models. The Polar Cusp campaign consisted of a single rocket launched from Cape Parry, Canada into the afternoon auroral zone at 1:31:13 UT on January 21, 1982. The results include the measurement of a narrow, magnetic field aligned electron flux at the edge of an arc. This electron precipitation was found to have a remarkably constant 1.2 eV temperature perpendicular to the magnetic field over a 200 to 900 eV energy range. The payload also made simultaneous measurements of both energetic electrons and 3-MHz plasma waves in an auroral arc. Analysis has shown that the waves are propagating in the upper hybrid band and should be generated by a positive slope in the parallel electron distribution. A correlation was found between the 3-MHz waves and small positive slopes in the parallel electron distribution but experimental uncertainties in the electron measurement were large enough to influence the analysis. The BIDARCA campaign consisted of two sounding rockets launched from Poker Flat and Fort Yukon, Alaska at 9:09:00 UT and 9:10:40 UT on February 7, 1984

A method to study electron heating during ICRH

International Nuclear Information System (INIS)

Eriksson, L.G.; Hellsten, T.

1989-01-01

Collisionless absorption of ICRF waves occurs either by ion cyclotron absorption or by electron Landau (ELD) and transit damping (TTMP). Both ion cyclotron absorption, and direct electron absorption results in electron heating. Electron heating by minority ions occurs after a high energy tail of the resonating ions has been formed i.e. typically after 0.2-1s in present JET experiments. Electron heating through ELD, and TTMP, takes place on the timescale given by electron-electron collisions which is typically of the order of ms. This difference in the timescales can be used to separate the two damping mechanisms. This can be done by measuring the time derivatives of the electron temperature after sawtooth crashes during ramp-up and ramp-down of the RF-power. (author) 4 refs., 4 figs

High pressure and synchrotron radiation studies of solid state electronic instabilities

International Nuclear Information System (INIS)

Pifer, J.H.; Croft, M.C.

1992-04-01

This report discusses Eu and General Valence Instabilities; Ce Problem: L 3 Spectroscopy Emphasis; Bulk Property Emphasis; Transition Metal Compound Electronic Structure; Electronic Structure-Phonon Coupling Studies; High Temperature Superconductivity and Oxide Materials; and Novel Materials Collaboration with Chemistry

Oxidation mechanism of nickel particles studied in an environmental transmission electron microscope

DEFF Research Database (Denmark)

Jeangros, Q.; Hansen, Thomas Willum; Wagner, Jakob Birkedal

2014-01-01

The oxidation of nickel particles was studied in situ in an environmental transmission electron microscope in 3.2 mbar of O2 between ambient temperature and 600°C. Several different transmission electron microscopy imaging techniques, electron diffraction and electron energy-loss spectroscopy were...... diffusion of Ni2+ along NiO grain boundaries, self-diffusion of Ni2+ ions and vacancies, growth of NiO grains and nucleation of voids at Ni/NiO interfaces. We also observed the formation of transverse cracks in a growing NiO film in situ in the electron microscope....

Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

Science.gov (United States)

Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

2015-10-01

As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

A Study of Electron Decay in Nitrogen Time After-glow

International Nuclear Information System (INIS)

Veis, P.; Coitout, H.; Magne, L.; Cernogora, G.

1999-01-01

This paper deals with electron density measurements in nitrogen time after-glow using hyper frequency resonant cavity. The studied pressures are from the range 9-530 Pa and discharge currents from 20 mA up to 500 mA. Electrons decreases up to the time of 1,4 ms in after-glow depending on pressure, pulse current and pulse duration (Authors)

Study of radiation-thermal effect of electron beam on steel and cast iron

International Nuclear Information System (INIS)

Machurin, E.S.; Lonchin, G.M.

1980-01-01

Studied is the influence of radiation-heat treatment by high energy (3-4.5 MeV) electron beam on the structure and properties of carbon steels (65G, 90KhF) and cast iron. Metallography and electron microscopy methods are used to study microstructure. It is shown that after the treatment by the electron beam there is observed noticeable structure grinding, sample fracture viscosity (even in a quenched state), increase of hardness and impact strength. The mechanism of metal heating process by electron beam is calculated and temperature field is defined in a heating region accounting for electron beam characteristics, medium and geometric factor. Theoretical data are close to experimental ones obtained in a course of determining the microhardness of irradiated samples for the cases of electron treatment duration up to 10 s

HOSPITAL INFORMATION SYSTEMS: A STUDY OF ELECTRONIC PATIENT RECORDS

Directory of Open Access Journals (Sweden)

Pedro Luiz Cortês

2011-05-01

Full Text Available The importance of patient records, also known as medical records, is related to different needs and objectives, as they constitute permanent documents on the health of patients. With the advancement of information technologies and systems, patient records can be stored in databases, resulting in a positive impact on patient care. Based on these considerations, a research question that arises is “what are the benefits and problems that can be seen with the use of electronic versions of medical records?” This question leads to the formulation of the following hypothesis: although problems can be identified during the process of using electronic record systems, the benefits outweigh the difficulties, thereby justifying their use. To respond to the question and test the presented hypothesis, a research study was developed with users of the same electronic record system, consisting of doctors, nurses, and administrative personnel in three hospitals located in the city of São Paulo, Brazil. The results show that, despite some problems in their usage, the benefits of electronic patient records outweigh possible disadvantages.

A comparative bioavailability study of two ibuprofen formulations after single-dose administration in healthy volunteers

Directory of Open Access Journals (Sweden)

Metta S.S. Wiria

2007-09-01

Full Text Available This study was aimed to investigate the bioequivalence of ibuprofen 125 mg suppository formulation (Ibukal®, test formulation from PT. Kalbe Farma, Tbk., Jakarta and the ibuprofen suppository comparative formulation (Proris®, from PT. Pharos Indonesia, Jakarta in 12 healthy volunteers. The pharmacokinetic parameters used in this study were the area under the concentration-time curve from time zero to hour 10 (AUC0-t, the area under the concentration-time curve from time zero to infinite (AUC0-inf, the maximum concentration (Cmax, and the time needed to reach the maximum concentration (tmax. The study was designed as a random cross-over fashion, single-blinded which included 12 healthy adult volunteers. The volunteers were fasted overnight and in the morning they received a suppository of the test drug (Ibukal® or a suppository of the comparative drug (Proris®. Blood samples were withdrawn on hour 0 (control, 20 min; 40 min; 1; 1.5; 2; 2.5; 3; 4; 6; 8; and 10 time points after the administration of the drug. Following a wash-out period of 1 week, this procedure was repeated using the other drug. The serum concentration of the drug was determined by means of high-performance liquid chromatography with ultraviolet detection. The results of the study showed that, the mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the test drug were, respectively, 28.59(3.37 μg.h.mL-1, 30.47(3.56 μg.h.mL-1, 8.24(1.44 μg/mL, and 1.33(0.44 h. The mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the comparative drug were, respectively, 28.13(8.14 μg.h.mL-1, 30.56(8.05 μg.h.mL-1, 8.27(2.88 μg/mL, and 1.79(0.33 h. The geometric means ratio of the test to the comparative drug were 104.38% (CI 90%: 90.38-120.54% for AUC0-t, 101.97% (CI 90%: 89.51-116.16% for AUC0-inf, and 104.02% (CI 90%: 85.73-126.16% for Cmax. There was no side effect of the drug detected in this study. From the results we can conclude that the 125 mg of ibuprofen suppository of PT Kalbe Farma

Electron Dropout Echoes Induced by Interplanetary Shock: A Statistical Study

Science.gov (United States)

Liu, Z.; Zong, Q.; Hao, Y.; Zhou, X.; Ma, X.; Liu, Y.

2017-12-01

"Electron dropout echo" as indicated by repeated moderate dropout and recovery signatures of the flux of energetic electron in the out radiation belt region has been investigated systematically. The electron dropout and its echoes are usually found for higher energy (> 300 keV) channels fluxes, whereas the flux enhancements are obvious for lower energy electrons simultaneously after the interplanetary shock arrives at the Earth's geosynchronous orbit. 104 dropout echo events have been found from 215 interplanetary shock events from 1998 to 2007 based on LANL satellite data. In analogy to substorm injections, these 104 events could be naturally divided into two categories: dispersionless (49 events) or dispersive (55 events) according to the energy dispersion of the initial dropout. It is found that locations of dispersionless events are distributed mainly in the duskside magnetosphere. Further, the obtained locations derived from dispersive events with the time-of-flight technique of the initial dropout regions are mainly located at the duskside as well. Statistical studies have shown that the effect of shock normal, interplanetary magnetic field Bz and solar wind dynamic pressure may be insignificant to these electron dropout events. We suggest that the electric field impulse induced by the IP shock produces a more pronounced inward migration of electrons at the dusk side, resulting in the observed dusk-side moderate dropout of electron flux and its consequent echoes.

Development of two electronic bladder diaries: a patient and healthcare professionals pilot study.

Science.gov (United States)

Mangera, Altaf; Marzo, Alberto; Heron, Nicola; Fernando, Dayan; Hameed, Khawar; Soliman, Abdel-Hamid A; Bradley, Mike; Hosking, Ian; Abdel-Maguid, Mohamed; Levermore, Martin; Tindale, Wendy B; Chapple, Christopher

2014-09-01

Assess patients' preferences in a pilot crossover study of two different electronic voiding diaries against a standard paper diary. Assess urological health professional (HP) opinions on the electronic bladder diary reporting system. Two different electronic diaries were developed: (1) electronically read diary-a card with predefined slots read by a card reader and (2) e-diary-a handheld touch screen device. Data uploaded from either electronic diary produced an electronic report. We recruited 22 patients split into two cohorts for each electronic diary, 11 completed each type of electronic diary for 3 days either preceded or followed by a standard paper diary for 3 days. Both diaries were completed on the 7th day. Patients' perceptions of both diaries were recorded using a standardized questionnaire. A HP study recruited 22 urologists who were given the paper diary and the electronic reports. Time taken for analysis was recorded along with accuracy and HP preferences. The majority of patients (82%) preferred the e-diary and only 1/11 found it difficult to use. Patients had the same preference for the electronically read diary as the paper diary. The paper diary took 66% longer to analyze than the electronic report (P analyzed with an accuracy of 58% compared to 100%. Slightly more HP (9%) preferred the electronic report to the paper diary. This proposed e-diary with its intuitive interface has overcome previous deficiencies in electronic diaries with most patients finding the format user-friendly. Electronic reports make analysis and interpretation by HP quicker and more accurate. © 2013 Wiley Periodicals, Inc.

A theoretical study of structural, opto-electronic and nonlinear properties of arylboroxine derivatives

Science.gov (United States)

Islam, Nasarul; Pandith, Altaf Hussain

2018-01-01

Density functional theory at CAM-B3LYP/6-311G++ (2d, 2p) level was employed to study the Triphenylboroxine derivatives ( TB) containing electron donating and electron substituents, for their charge transfer and nonlinear optical properties. The results reveal that electron donating groups facilitate the rapid electron injection as compared to unsubstituted TB. It was observed that upon substitution with electron donating groups, the TB derivatives show an increased double bond character in the B3-C18 bond indicating an increase in the degree of conjugation. The Frontier molecular orbital studies indicate that highest occupied molecular orbitals of the neutral molecules delocalize primarily over the three phenyl rings and bridging oxygen atoms, whereas the lowest unoccupied molecular orbitals localize largely on the two phenyl rings and the boron atoms. Further, the TD-DFT studies indicate that the maximum absorption band results from the electron transitions from the initial states that are contributed by the HOMO and HOMO-1 to the final states that are mainly contributed by the LUMOs. In addition, we have observed that the introduction of electron donating group to the TB-7 leads to more active nonlinear performance.

Role of electron swarm studies in the development of gaseous dielectrics

International Nuclear Information System (INIS)

Christophorou, L.G.

1981-01-01

Recent knowledge provided by swarm studies allowing control of the number densities and energies of free electrons in electrically stressed gases is highlighted. This knowledge aided the discovery of new gas dielectrics and the tailoring of gas dielectric mixtures. The role of electron attachment in the choice of unitary gas dielectrics or electronegative components in dielectric gas mixtures, and the role of electron scattering at low energies in the choice of buffer gases for mixtures is outlined

Study of Scanning Tunneling Microscope control electronics

International Nuclear Information System (INIS)

Oliva, A.J.; Pancarobo, M.; Denisenko, N.; Aguilar, M.; Rejon, V.; Pena, J.L.

1994-01-01

A theoretical study of Scanning Tunneling Microscope control electronics is made. The knowledge of its behaviour allows us to determine accurately the region where the unstable operation could effect the measurements, and also to set the optimal working parameters. Each feedback circuitry compound is discussed as well as their mutual interaction. Different working conditions analysis and results are presented. (Author) 12 refs

[Troubleshooting of bioinequivalence of compound valsartan tablets].

Science.gov (United States)

Shao, Da; Zhang, Yi-Fan; Zhan, Yan; Chen, Xiao-Yan; Zhong, Da-Fang

2014-04-01

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

Studies of dynamics of electron clouds in STAR silicon drift detectors

CERN Document Server

Bellwied, R; Brandon, N; Caines, H; Chen, W; Dimassimo, D; Dyke, H; Hall, J R; Hardtke, D; Hoffmann, G W; Humanic, T J; Kotova, A I; Kotov, I V; Kraner, H W; Li, Z; Lynn, D; Middelkamp, P; Ott, G; Pandey, S U; Pruneau, C A; Rykov, V L; Schambach, J; Sedlmeir, J; Sugarbaker, E R; Takahashi, J; Wilson, W K

2000-01-01

The dynamics of electrons generated in silicon drift detectors was studied using an IR LED. Electrons were generated at different drift distances. In this way, the evolution of the cloud as a function of drift time was measured. Two methods were used to measure the cloud size. The method of cumulative functions was used to extract the electron cloud profiles. Another method obtains the cloud width from measurements of the charge collected on a single anode as a function of coordinate of the light spot. The evolution of the electron cloud width with drift time is compared with theoretical calculations. Experimental results agreed with theoretical expectations.

Head-facial hemangiomas studied with scanning electron microscopy.

Science.gov (United States)

Cavallotti, Carlo; Cavallotti, Chiara; Giovannetti, Filippo; Iannetti, Giorgio

2009-11-01

Hemangiomas of the head or face are a frequent vascular pathology, consisting in an embryonic dysplasia that involves the cranial-facial vascular network. Hemangiomas show clinical, morphological, developmental, and structural changes during their course. Morphological, structural, ultrastructural, and clinical characteristics of head-facial hemangiomas were studied in 28 patients admitted in our hospital. Nineteen of these patients underwent surgery for the removal of the hemangiomas, whereas 9 patients were not operated on. All the removed tissues were transferred in our laboratories for the morphological staining. Light microscopy, transmission electron microscopy, and scanning electron microscopy techniques were used for the observation of all microanatomical details. All patients were studied for a clinical diagnosis, and many were subjected to surgical therapy. The morphological results revealed numerous microanatomical characteristics of the hemangiomatous vessels. The observation by light microscopy shows the afferent and the efferent vessels for every microhemangioma. All the layers of the arterial wall are uneven. The lumen of the arteriole is entirely used by a blood clot. The observation by transmission electron microscopy shows that it was impossible to see the limits of the different layers (endothelium, medial layer, and adventitia) in the whole wall of the vessels. Moreover, both the muscular and elastic components are disarranged and replaced with connective tissue. The observation by scanning electron microscopy shows that the corrosion cast of the hemangioma offers 3 periods of filling: initially with partial filling of the arteriolar and of the whole cast, intermediate with the entire filling of the whole cast (including arteriole and venule), and a last period with a partial emptying of the arteriolar and whole cast while the venule remains totally injected with resin. Our morphological results can be useful to clinicians for a precise

Study of electron-positron interactions

International Nuclear Information System (INIS)

Abashian, A.; Gotow, K.; Philonen, L.

1990-01-01

For the past seven years, this group has been interested in the study of tests of the Standard Model of Electroweak interactions. The program has centered about the AMY experiment which examines the nature of the final state products in electron-positron collisions in the center of mass energy range near 60 GeV. Results of these measurements have shown a remarkable consistency with the predictions of the minimal model of 3 quark and lepton generations and single charged and neutral intermediate bosons. No new particles or excited states have been observed nor has any evidence for departures in cross sections or angular asymmetries from expectations been observed. These conclusions have been even more firmly established by the higher energy results from the LEP and SLC colliders at center of mass energies of about 90 GeV. Our focus is shifting to the neutrino as a probe to electroweak interactions. The relative merit of attempting to observe neutrinos from point sources versus observing neutrinos generally is not easy to predict. The improved ability to interpret is offset by the probably episodic nature of the emission and irreproducibility of the results. In this phase of development, it is best to be sensitive to both sources of neutrinos. As a second phase of our program at Virginia Tech, we are studying the feasibility of detecting cosmic ray neutrinos in a proposed experiment which we have called NOVA. the results of the test setup will be instrumental in developing an optimum design. A third program we are involved in is the MEGA experiment at Los Alamos, an experiment to place a limit on the rate of muon decay to electron plus photon which is forbidden by the Standard Model

Preliminary Design Study of the Hollow Electron Lens for LHC

CERN Document Server

Perini, Diego; CERN. Geneva. ATS Department

2017-01-01

A Hollow Electron Lens (HEL) has been proposed in order to improve performance of halo control and collimation in the Large Hadron Collider in view of its High Luminosity upgrade (HL-LHC). The concept is based on a beam of electrons that travels around the protons for a few meters. The electron beam is produced by a cathode and then guided by a strong magnetic field generated by a set of superconducting solenoids. The first step of the design is the definition of the magnetic fields that drive the electron trajectories. The estimation of such trajectories by means of a dedicated MATLAB® tool is presented. The influence of the main geometrical and electrical parameters are analysed and discussed. Then, the main mechanical design choices for the solenoids, cryostats gun and collector are described. The aim of this paper is to provide an overview of the preliminary design of the Electron Lens for LHC. The methods used in this study also serve as examples for future mechanical and integration designs of similar ...

Study on the compensation of electron beam space charge in facilittes with electron cooling

International Nuclear Information System (INIS)

Dikanskij, N.S.; Kudelajnen, V.I.; Parkhomchuk, V.V.; Pestrikov, D.V.

1981-01-01

The results of experimental investigations of a compensated electron beam on the NAP-M facility are presented. The electron beam is compensated by electrostatic plugs preventing ion leakage along the beam. Cut-off electrodes have the shape of cutted cylinders encircling the electron beam. To eliminate electron accumulation around the plugs one of the electrodes has a zero potential, which results in formation of an transverse electric field causing ionization electron drift in the transverse direction to the electric and magnetic fields. The effect of wave damping, in the compensated beam is observed, that demonstrates the possibility of gaining great current densities in long compensated beams necessary for antiproton storage. For the NAP-M at the 10 10 cm/s electron velocity, 300 cm length of ion column, and 1 kOe field intensity the threshold beam current density is 0.96 A/cm 2 [ru

Electron and photon impact studies of CF3I

International Nuclear Information System (INIS)

Mason, N.J.; Eden, S.; Limao Vieire, P.; Kendall, P.; Pathak, S.; Dawes, A.; Tegeder, P.; Kitajima, M.; Okamoto, M.; Tanaka, H.; Samukawa, S.; Cho, H.; Hoffmann, S.

2002-01-01

The manufacture of ultra-large-scale-integrated circuits, requires a well collimated, specially uniform, high density plasma source operating under low pressure conditions. The main feed gases used are perfluorocarbons, however these are also strong greenhouse gases, therefore must be replaced by alternative compounds with low global warming potentials. CF 3 I is one possible replacement, due to its high photolysis rate, is expected to have a very short lifetime in the atmosphere. It is also predicted to be able to produced high yields of CF 3 radicals in any etching plasma, since its weak C - I bond should be possible to break by direct electron impact. Prior adapting existing industrial plasma reactors to use CF 3 I, it is necessary to run simulations of the reactant plasma, requiring a detailed database of the electron interactions with the feed gases, however such CF 3 I data does not exist. Thus an exhaustive series of experiments to measure elastic and inelastic scattering from CF 3 I including a study of its electronic state spectroscopy using photon absorption and electron scattering techniques were performed. Electron energy loss spectroscopy (EELS) and photo-absorption spectroscopy were employed. A comprehensive set of differential cross sections for the elastic scattering CF 3 I over the impact energy region from 1.5 to 60 eV for scattering angles between 20 and 130 were compiled. The photo-absorption spectrum is characterized by three regions, the first is a very weak continuum around centered about 4.7 eV; the second consists of four prominent band structures observed around 7.4, 8.1, 9.0 and 9.8 eV, respectively, containing vibrational structure from 7 to 10 eV; the third (above the ionization potentials) could only be studied by using EELS and additional broad peaks were observed. (nevyjel)

Electron beam interactions with CO on W[100] studied by Auger electron spectroscopy

International Nuclear Information System (INIS)

Housley, M.; King, D.A.

1977-01-01

The interaction of 2500 eV electrons with carbon monoxide chemisorbed on tungsten [100] was investigated by rapid-scan Auger electron spectroscopy. When no α state was present the O and C signals from the β state of CO were invariant during electron bombardment, giving an upper limit estimate for the electron stimulated desorption cross section, Qsub(β), of 2 x 10 -21 cm 2 . With the crystal at room temperature and saturated with CO, however, electron-beam induced accumulation of carbon was observed and characterised, the rate of the process being independent of CO pressure at pressures above 2 x 10 -8 Torr. At 450 K the rate was found to be pressure dependent up to at least 6 x 10 -7 Torr. A model is proposed for the accumulation process, which is based on electron beam dissociation of α 2 -CO to form adsorbed carbon and gaseous O and the creation of new sites for further α 2 -CO adsorption; it is in quantitative agreement with the results and yields a cross section for ESD of α 2 -CO (Qsub(α 2 )=1.55 X 10 -18 cm 2 ) in clo 2 e agreement with direct measurements. (Auth.)

Monte Carlo studies of thermalization of electron-hole pairs in spin-polarized degenerate electron gas in monolayer graphene

Science.gov (United States)

Borowik, Piotr; Thobel, Jean-Luc; Adamowicz, Leszek

2018-02-01

Monte Carlo method is applied to the study of relaxation of excited electron-hole (e-h) pairs in graphene. The presence of background of spin-polarized electrons, with high density imposing degeneracy conditions, is assumed. To such system, a number of e-h pairs with spin polarization parallel or antiparallel to the background is injected. Two stages of relaxation: thermalization and cooling are clearly distinguished when average particles energy and its standard deviation σ _E are examined. At the very beginning of thermalization phase, holes loose energy to electrons, and after this process is substantially completed, particle distributions reorganize to take a Fermi-Dirac shape. To describe the evolution of and σ _E during thermalization, we define characteristic times τ _ {th} and values at the end of thermalization E_ {th} and σ _ {th}. The dependence of these parameters on various conditions, such as temperature and background density, is presented. It is shown that among the considered parameters, only the standard deviation of electrons energy allows to distinguish between different cases of relative spin polarizations of background and excited electrons.

Runaway electron transport studies in the HL-1M tokamak

International Nuclear Information System (INIS)

Zheng Yongzhen; Qi Changwei; Ding Xuantong; Li Wenzhong

2002-01-01

The transport of runaway electrons in a hot plasma has been studied in four experiments, which provide the runaway diffusivity D r The first experiment obtained runaway electrons using a steady state approach for values of the runaway confinement time τ r , deduced from hard X-ray bremsstrahlung spectra. In the second experiment, diffusion has been interpreted in terms of the magnetic fluctuation, from which a electron thermal diffusivity can be deduced. Runaway electro diffusion coefficient is determined by intrinsic magnetic fluctuations, rather than electrostatic fluctuations because of the high energy involved. The results presented here demonstrate the efficiency of using runaway transport techniques for determining intrinsic magnetic fluctuations

Role of hot electron transport in scintillators: A theoretical study

Energy Technology Data Exchange (ETDEWEB)

Huang, Huihui [SZU-NUS Collaborative Innovation Center for Optoelectronic Science and Technology, Key Lab. of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen Univ. (China); Li, Qi [Physical Sciences Division, IBM TJ Watson Research Center, Yorktown Heights, NY (United States); Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL (United States); Lu, Xinfu; Williams, R.T. [Department of Physics, Wake Forest University, Winston Salem, NC (United States); Qian, Yiyang [College of Engineering and Applied Science, Nanjing University (China); Wu, Yuntao [Scintillation Materials Research Center, University of Tennessee, Knoxville, TN (United States)

2016-10-15

Despite recent intensive study on scintillators, several fundamental questions on scintillator properties are still unknown. In this work, we use ab-initio calculations to determine the energy dependent group velocity of the hot electrons from the electronic structures of several typical scintillators. Based on the calculated group velocities and optical phonon frequencies, a Monte-Carlo simulation of hot electron transport in scintillators is carried out to calculate the thermalization time and diffusion range in selected scintillators. Our simulations provide physical insights on a recent trend of improved proportionality and light yield from mixed halide scintillators. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Numerical studies of electron dynamics in oblique quasi-perpendicular collisionless shock waves

International Nuclear Information System (INIS)

Liewer, P.C.; Decyk, V.K.; Dawson, J.M.; Lembege, B.

1991-01-01

Linear and nonlinear electron damping of the whistler precursor wave train to low Mach number quasi-perpendicular oblique shocks is studied using a one-dimensional electromagnetic plasma simulation code with particle electrons and ions. In some parameter regimes, electrons are observed to trap along the magnetic field lines in the potential of the whistler precursor wave train. This trapping can lead to significant electron heating in front of the shock for β e (∼10% or less). Use of the 64-processor Caltech/JPL Mark IIIfp hypercube concurrent computer has enables us to make long runs using realistic mass ratios (m i /m e = 1,600) in the full particle in-cell code and thus simulate shock parameter regimes and phenomena not previously studied numerically

Structural defects in multiferroic BiMnO3 studied by transmission electron microscopy and electron energy-loss spectroscopy

International Nuclear Information System (INIS)

Yang, H.; Chi, Z. H.; Yao, L. D.; Zhang, W.; Li, F. Y.; Jin, C. Q.; Yu, R. C.

2006-01-01

The multiferroic material BiMnO 3 synthesized under high pressure has been systematically studied by transmission electron microscopy and electron energy-loss spectroscopy, and some important structural defects are revealed in this multiferroic material. The frequently observed defects are characterized to be Σ3(111) twin boundaries, Ruddlesden-Popper [Acta Crystallogr. 11, 54 (1958)] antiphase boundaries, and a p p superdislocations connected with a small segment of Ruddlesden-Popper defect. These defects are present initially in the as-synthesized sample. In addition, we find that ordered voids (oxygen vacancies) are easily introduced into the multiferroic BiMnO 3 by electron-beam irradiation

Generation and study of relativistic electron beam

International Nuclear Information System (INIS)

Iyyengar, S.K.; Ron, P.H.; Mittal, K.C.; Goel, A.K.; Ramaswamy, V.; Rohatgi, V.K.

1977-01-01

Pulsed Electron Beam (REB) technology has progressed rapidly in recent years because of applications in various fields like radiation sources, high power laser development, plasma heating and fusion research. The REB development programme at the Plasma Physics Section of Bhabha Atomic Research Centre, Bombay, has been described. The design features of the 375 KV, 3500 A, 75 Joule REB generator are discussed. The diagnostic equipment developed for the studies is described. The present experimental studies and some preliminary results on beam characterisation are presented. (author)

A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

Science.gov (United States)

Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

2017-12-01

Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

Gemstone color enhancement by electron beam irradiation-A preliminary study

International Nuclear Information System (INIS)

Sarada Idris; Zulkafli Ghazali; Shamshad Ahmad; Mohd Suhaimi Jusoh

2010-01-01

Treatment of gemstones has been going on for hundreds of years for enhancing color and clarity of gems devoid of these attributes. Whereas previous practices included fraudulent or otherwise processes to achieve the color enhancement, the ionizing radiation has proven to be a reliable and reproducible technique. Three types of irradiation processes include exposure to gamma radiation, electron beam irradiation and the nuclear power plants. Electron Beam Irradiation of Gemstone is a technique in which a gemstone is exposed to highly ionizing radiation electron beam to knock off electrons to generate color centers culminating in introduction of deeper colors. The color centers may be stable or unstable. Below 9 MeV, normally no radioactivity is introduced in the exposed gems. A study was conducted at Electron Beam Irradiation Centre (Alurtron) for gemstone color enhancement by using different kind of precious gemstones mined in Pakistan and elsewhere. The study shows that EB Irradiation not only enhances the color but also improves the clarity of the gemstones. The treated stones included kunzite tourmaline topaz quartz aquamarine and cultured pearls. Doses ranging from 25 kGy to 200 kGy were employed to assess the influence of doses on color and clarity and to select the optimum doses. The samples used included both the rough and the faceted gems. It is concluded that significant revenue generation is associated with the enhancement of the color in clarity of gemstones which are available at very cheap price in the world market. (author)

Electron Cloud Parameterization Studies in the LHC

CERN Document Server

Dominguez, O; Baglin, V; Bregliozzi, G; Jimenez, J M; Metral, E; Rumolo, G; Schulte, D; Zimmermann, F

2011-01-01

During LHC beam commissioning with 150, 75 and 50-ns bunch spacing, important electron-cloud effects, like pressure rise, cryogenic heat load, beam instabilities or emittance growth, were observed. The main strategy to combat the LHC electron cloud, defined about ten years ago, relies on the surface conditioning arising from the chamber-surface bombardment with cloud electrons. In a standard model, the conditioning state of the beam-pipe surface is characterized by three parameters: 1. most importantly, the secondary emission yield δmax; 2. the incident electron energy at which the yield is maximum, ε_max; and 3. the probability of elastic reflection of low-energy primary electrons hitting the chamber wall, R. Since at the LHC no in-situ secondary-yield measurements are available, we compare the relative local pressure-rise measurements taken for different beam configurations against simulations in which surface parameters are scanned. This benchmarking of measurements and simulations is used to infer the s...

5-D simulation study of suprathermal electron transport in non-axisymmetric plasmas

International Nuclear Information System (INIS)

Murakami, S.; Idei, H.; Kubo, S.; Nakajima, N.; Okamoto, M.; Gasparino, U.; Maassberg, H.; Rome, M.; Marushchenko, N.

2000-01-01

ECRH driven transport of suprathermal electrons is studied in non-axisymmetric plasmas using a new Monte Carlo simulation technique in 5-D phase space. Two different phases of the ECRH driven transport of suprathermal electrons can be seen. The first is a rapid convective phase due to the direct radial motion of trapped electrons and the second is a slower phase due to the collisional transport. The important role of the radial transport of suprathermal electrons in the broadening of the ECRH deposition profile in W7-AS is clarified. The ECRH driven flux is also evaluated and considered in relation to the 'electron root' feature recently observed in W7-AS. It is found that, at low collisionalities, the ECRH driven flux due to the suprathermal electrons can play a dominant role in the condition of ambipolarity, and thus the observed electron root feature in W7-AS is thought to be driven by the radial (convective) flux of ECRH generated suprathermal electrons. A possible scenario for this type of electron root is considered for the LHD plasma. (author)

5D simulation study of suprathermal electron transport in non-axisymmetric plasmas

International Nuclear Information System (INIS)

Murakami, S.; Idei, H.; Kubo, S.; Nakajima, N.; Okamoto, M.; Gasparino, U.; Maassberg, H.; Rome, M.; Marushchenko, N.

1999-01-01

ECRH-driven transport of suprathermal electrons is studied in non-axisymmetric plasmas using a new Monte Carlo simulation technique in 5D phase space. Two different phases of the ECRH-driven transport of suprathermal electrons can be seen; one is a rapid convective phase due to the direct radial motion of trapped electrons and the other is a slower phase due to the collisional transport. The important role of the radial transport of suprathermal electrons in the broadening of the ECRH deposition profile is clarified in W7-AS. The ECRH driven flux is also evaluated and put in relation with the 'electron root' feature recently observed in W7-AS. It is found that, at low collisionalities, the ECRH driven flux due to the suprathermal electrons can play a dominant role in the condition of ambipolarity and, thus, the observed 'electron root' feature in W7-AS is thought to be driven by the radial (convective) flux of ECRH generated suprathermal electrons. The possible scenario of this 'ECRH-driven electron root' is considered in the LHD plasma. (author)

Preliminary Mechanical Design Study of the Hollow Electron Lens for HL-LHC

Science.gov (United States)

Zanoni, Carlo; Gobbi, Giorgia; Perini, Diego; Stancari, Giulio

2017-07-01

A Hollow Electron Lens (HEL) has been proposed in order to improve performance of halo control and collimation in the Large Hadron Collider in view of its High Luminosity upgrade (HL-LHC). The concept is based on a hollow beam of electrons that travels around the protons for a few meters. The electron beam is produced by a cathode and then guided by a strong magnetic field. The first step of the design is the definition of the magnetic field that drives the electron trajectories. The estimation of such trajectories by means of a dedicated MATLAB tool is presented. The influence of the main geometrical and electrical parameters is analyzed and discussed. Then, the main mechanical design choices for the solenoids, cryostats gun and collector are described. The aim of this paper is to provide an overview of the feasibility study of the Electron Lens for LHC. The methods used in this study also serve as examples for future mechanical and integration designs of similar devices.

Preliminary Mechanical Design Study of the Hollow Electron Lens for HL-LHC

Energy Technology Data Exchange (ETDEWEB)

Zanoni, Carlo [CERN; Gobbi, Giorgia [CERN; Perini, Diego [CERN; Stancari, Giulio [Fermilab

2017-05-01

A Hollow Electron Lens (HEL) has been proposed in order to improve performance of halo control and collimation in the Large Hadron Collider in view of its High Luminosity upgrade (HL-LHC). The concept is based on a hollow beam of electrons that travels around the protons for a few meters. The electron beam is produced by a cathode and then guided by a strong magnetic field. The first step of the design is the definition of the magnetic field that drives the electron trajectories. The estimation of such trajectories by means of a dedicated MATLAB tool is presented. The influence of the main geometrical and electrical parameters is analyzed and discussed. Then, the main mechanical design choices for the solenoids, cryostats gun and collector are described. The aim of this paper is to provide an overview of the feasibility study of the Electron Lens for LHC. The methods used in this study also serve as examples for future mechanical and integration designs of similar devices.

Electronic structure studies of fullerites and fullerides

International Nuclear Information System (INIS)

Merkel, M.; Sohmen, E.; Masaki, A.; Romberg, H.; Alexander, M.; Knupfer, M.; Golden, M.S.; Adelmann, P.; Renker, B.; Fink, J.

1993-01-01

The electronic structure of fullerites and fullerides has been investigated by high-resolution photoemission and by high-energy electron energy-loss spectroscopy in transmission. Information on the occupied Π and σ bands, on the unoccupied Π * and σ * bands, and on the joint density of states has been obtained. In particular, we report on the changes of the electronic structure of fullerides as a function of dopant concentration. (orig.)

Theoretical study of electronic transport properties of a graphene-silicene bilayer

Energy Technology Data Exchange (ETDEWEB)

Berdiyorov, G. R. [Qatar Environment and Energy Research Institute, Qatar Foundation, P.O. Box 5825, Doha (Qatar); Bahlouli, H. [Department of Physics, King Fahd University of Petroleum and Minerals, 31261 Dhahran (Saudi Arabia); Saudi Center for Theoretical Physics, 31261 Dhahran (Saudi Arabia); Peeters, F. M. [Departement Fysica, Universiteit Antwerpen, Groenenborgerlaan 171, B-2020 Antwerpen (Belgium)

2015-06-14

Electronic transport properties of a graphene-silicene bilayer system are studied using density-functional theory in combination with the nonequilibrium Green's function formalism. Depending on the energy of the electrons, the transmission can be larger in this system as compared to the sum of the transmissions of separated graphene and silicene monolayers. This effect is related to the increased electron density of states in the bilayer sample. At some energies, the electronic states become localized in one of the layers, resulting in the suppression of the electron transmission. The effect of an applied voltage on the transmission becomes more pronounced in the layered sample as compared to graphene due to the larger variation of the electrostatic potential profile. Our findings will be useful when creating hybrid nanoscale devices where enhanced transport properties will be desirable.

Electronic transport study in PAMAM dendrimers

International Nuclear Information System (INIS)

Vieira, Nirton C.S.; Soares, Demetrio A.W.; Fernandes, Edson G.R.; Queiroz, Alvaro A.A. de

2005-01-01

Dendrimers are nanomaterials that have many potential applications in medicine, including diagnosis and therapeutic procedures. Dendrimers are isomolecular polymers, with a very well controlled architecture and a thousand times smaller than cells. Dendrimers containing biocatalysts are of great interest for clinical applications in biosensors because of the way in which their chemical and electric conduction mechanism can be tailored. In this work, the polyamidoamine dendrimer (PAMAM) of generation 4 was synthesized by divergent route and characterized by NMR spectroscopy. The electronic transport properties of PAMAM in a metal-polymer type heterojunction were studied. The electrical conduction mechanism of PAMAM studied in the temperature range of 291-323 K indicates a conduction mechanism thermally activated. (author)

#Vapelife: An Exploratory Study of Electronic Cigarette Use and Promotion on Instagram.

Science.gov (United States)

Laestadius, Linnea I; Wahl, Megan M; Cho, Young I

2016-10-14

The growth of social networking services has enabled the sharing of electronic cigarette opinions and experiences via user-generated content. This exploratory study analyzed electronic cigarette content found on the visual social networking service, Instagram, in order to highlight public health challenges created by this content and support understanding of electronic cigarette promotion and usage. A qualitative content analysis was performed on Instagram posts made with the hashtags #ecig or #vape in October 2014. Images, text, and hashtags from 85 posts (43 #ecig, 42 #vape) were analyzed. In addition, the total number of posts made with eight key electronic cigarette hashtags was recorded at four points between March 2014 and October 2015. The total number of #vape posts on Instagram grew by 4,163,274 during the study period, while #ecig posts increased by 741,916. Of the posts examined in-depth, corporate users made up over half of posts. No posts were critical of electronic cigarettes. Few mentioned electronic cigarettes in the context of health benefits. No posts included major brands, and mod style electronic cigarettes were mentioned or depicted in over half of posts. A majority of posts included hashtags expressing vaping identity and community. In addition, users mentioned novel practices such as sub-ohming. Conclusions/Importance: Instagram users in our sample characterized electronic cigarettes primarily as novel devices rather than equivalents to cigarettes. Further, hashtag communities and identities appear to be forming around vaping. Future research should consider the public health implications of these hashtags, as well as novel electronic cigarette practices.

Electronic and optical properties of Fe, Pd, and Ti studied by reflection electron energy loss spectroscopy

International Nuclear Information System (INIS)

Tahir, Dahlang; Kraaer, Jens; Tougaard, Sven

2014-01-01

We have studied the electronic and optical properties of Fe, Pd, and Ti by reflection electron energy-loss spectroscopy (REELS). REELS spectra recorded for primary energies in the range from 300 eV to 10 keV were corrected for multiple inelastically scattered electrons to determine the effective inelastic-scattering cross section. The dielectric functions and optical properties were determined by comparing the experimental inelastic-electron scattering cross section with a simulated cross section calculated within the semi-classical dielectric response model in which the only input is Im(−1/ε) by using the QUEELS-ε(k,ω)-REELS software package. The complex dielectric functions ε(k,ω), in the 0–100 eV energy range, for Fe, Pd, and Ti were determined from the derived Im(−1/ε) by Kramers-Kronig transformation and then the refractive index n and extinction coefficient k. The validity of the applied model was previously tested and found to give consistent results when applied to REELS spectra at energies between 300 and 1000 eV taken at widely different experimental geometries. In the present paper, we provide, for the first time, a further test on its validity and find that the model also gives consistent results when applied to REELS spectra in the full range of primary electron energies from 300 eV to 10000 eV. This gives confidence in the validity of the applied method.

Electron microscopy studies on MoS2 nanocrystals

DEFF Research Database (Denmark)

Hansen, Lars Pilsgaard

Industrial-style MoS2-based hydrotreating catalysts are studied using electron microscopy. The MoS2 nanostructures are imaged with single-atom sensitivity to reveal the catalytically important edge structures. Furthermore, the in-situ formation of MoS2 crystals is imaged for the first time....

An experimental study of electron transfer and emission during particle-surface interactions

International Nuclear Information System (INIS)

McGrath, C.T.

2000-09-01

A new coincidence technique has been developed and used to study the secondary electron emission that arises during the interaction of ions with surfaces. This coincidence technique allows the secondary electron emission statistics due to the impact of singly, doubly and multiply charged ions on surfaces to be measured in coincidence with reflected particles, in specific charge states and with specific post-collision trajectories. This system has been used to study the impact of 8 keV H + ions on polycrystalline copper and aluminium targets. Under these conditions the potential emission contribution is negligible and the electron emission is almost entirely due to kinetic emission processes. The sub-surface contribution to the observed electron emission has been isolated using two newly developed models. These models provide valuable information about the depth and amount of surface penetration and on the probability for subsequent electron transport to the surface. The impact of 2 - 100 keV Xe q+ (q = 1 - 10) ions on polycrystalline copper has also been studied using this system. From the subsequent data the potential and kinetic contributions to secondary electron emission have been separated using a previously established model for potential emission. The resulting kinetic emission yield increases with increasing ion impact energy, consistent with current concepts on quasimolecular ionisation. For ions impacting at large incident angles evidence for sub-surface emission has also been observed. The degree of penetration increases with ion impact energy, consistent with current concepts on this effect. The formation of H - ions from incident H + ions has also been studied by measuring the secondary electron emission statistics in coincidence with reflected particles in specific final charge states. This preliminary data is consistent with a two-step process of Auger neutralisation followed by resonant electron capture to the affinity level. However this mechanism

Study of absorbed dose distribution to high energy electron beams

International Nuclear Information System (INIS)

Cecatti, E.R.

1983-01-01

The depth absorbed dose distribution by electron beams was studied. The influence of the beam energy, the energy spread, field size and design characteristics of the accelerator was relieved. Three accelerators with different scattering and collimation systems were studied leading todifferent depth dose distributions. A theoretical model was constructed in order to explain the increase in the depth dose in the build-up region with the increase of the energy. The model utilizes a three-dimensional formalism based on the Fermi-Eyges multiple scattering theory, with the introduction of modifications that takes into account the criation of secondary electrons. (Author) [pt

Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

Science.gov (United States)

Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

2017-05-23

Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

Status of experimental studies of electron cloud effects at the Los Alamos proton storage ring

International Nuclear Information System (INIS)

Macek, R.J.; Browman, A.A.; Borden, M.J.; Fitzgerald, D.H.; McCrady, R.C.; Spickermann, T.J.; Zaugg, T.J.

2004-01-01

Various electron cloud effects (ECE) including the two-stream (e-p) instability at the Los Alamos Proton Storage Ring (PSR) have been studied extensively for the past five years with the goal of understanding the phenomena, mitigating the instability and ultimately increasing beam intensity. The specialized diagnostics used in the studies are two types of electron detectors, the retarding field analyzer and the electron sweepmg detector - which have been employed to measure characteristics of the electron cloud as functions of time, location in the ring and various influential beam parameters - plus a short stripline beam position monitor used to measure high frequency motion of the beam centroid. Highlights of this research program are summarized along with more detail on recent results obtained since the ECLOUD'02 workshop. Recent work mcludes a number of parametric studies of the various factors that affect the electron cloud signals, studies of the sources of initial or 'seed' electrons, additional observations of electron cloud dissipation after the beam pulse is extracted, studies of the 'first pulse instability' issue, more data on electron suppression as a cure for the instability, and observations of the effect of a one-turn weak kick on intense beams in the presence of a significant electron cloud.

Theoretical studies of atomic and quasiatomic excitations by electron and ion impact

International Nuclear Information System (INIS)

Kam, K.F.

1999-09-01

Electron emission from ion induced excitations of Ca, Sc, Ti and V metal surfaces and from electron impact on transition metal oxides CoO and TiO 2 has been studied in this thesis. Both the autoionising emission from sputtered atoms and the 3p→3d and 3s→3d excitations in the oxides reveal strong atomic features. The work has involved explaining these spectra in an atomic approach, via the use of atomic structure calculations, cross section studies and empirical/semi-empirical analyses. The other aspect of this work involves extension of current theories of electron-atom scattering in the high electron energy impact regime. Overall it is shown that much can be learned about some solid-state spectra by relating them to atomic phenomena. (author)

Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

Science.gov (United States)

Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

2013-11-01

Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

Use of electronic cigarettes among Romanian university students: a cross-sectional study.

Science.gov (United States)

Lotrean, Lucia Maria

2015-04-11

Because electronic cigarettes are relatively new, data on usage patterns and factors which influence them are sparse. Hence, this study aims at assessing awareness, beliefs about electronic cigarettes and experimentation with them among university students from Romania- a country where the sales and marketing of these products are widespread. Secondly, correlates of electronic cigarette experimentation will also be investigated. A cross-sectional study was performed by means of anonymous questionnaires among 480 students, aged 19-24, from Cluj-Napoca, Romania, between April-May 2013. The results show that 92.5% of the students have heard about e-cigarettes; out of these, one quarter (53.3% of the smokers, 25% of the ex-smokers, 5.5% of the non-smokers) have tried electronic cigarettes at least once during lifetime. The results of the multinomial logistic regression point out that the correlates of electronic cigarette experimentation were: male gender, being a smoker of traditional cigarettes, having friends who experimented with electronic cigarettes, having stronger beliefs that electronic cigarettes could help them quit smoking and being less convinced that they are used only by smokers. The explained variance was 59%. The results underline the importance of addressing the issue of e-cigarette use through health education programs and regulatory interventions, since e-cigarettes are a reality faced by the Romanian youth.

Study of the niobium dehydrogenation process by transmission electron microscopy

International Nuclear Information System (INIS)

Bulhoes, I.A.M.; Akune, K.

1983-01-01

The evolution of the micro-structure of Nb-H, during the dehydrogenation process through thermal treatment, has been studied by Transmission Electron Microscopy. The results are used in order to interpret the variation of the line resolution of Electron Channeling Pattern (ECP) of Nb-H as a function of isochronous annealing temperature. It is concluded that the improvement of the ECP line resolution is enhanced of β hydrate in Nb. (Author) [pt

5D simulation study of suprathermal electron transport in non-axisymmetric plasmas

International Nuclear Information System (INIS)

Murakami, S.; Idei, H.; Kubo, S.; Nakajima, N.; Okamoto, M.; Gasparino, U.; Maassberg, H.; Rome, M.; Marushchenko, N.

2001-01-01

ECRH-driven transport of is studied in using a new Monte Carlo simulation technique in 5D phase space. Two different phases of the ECRH-driven transport of suprathermal electrons can be seen; one is a rapid convective phase due to the direct radial motion of trapped electrons and the other is a slower phase due to the collisional transport. The important role of the radial transport of suprathermal electrons in the broadening of the ECRH deposition profile is clarified in W7-AS. The ECRH driven flux is also evaluated and put in relation with the ''electron root'' feature recently observed in W7-AS. It is found that, at low collisionalities, the ECRH driven flux due to the suprathermal electrons can play a dominant role in the condition of ambipolarity and, thus, the observed ''electron root'' feature in W7-AS is thought to be driven by the radial (convective) flux of ECRH generated suprathermal electrons. The possible scenario of this ''ECRH-driven electron root'' is considered in the LHD plasma. (author)

A Comparative Study of Electronic Performance Support Systems

Science.gov (United States)

Nguyen, Frank; Klein, James D.; Sullivan, Howard

2005-01-01

Electronic performance support systems (EPSS) deliver relevant support information to users while they are performing tasks. The present study examined the effect of different types of EPSS on user performance, attitudes, system use and time on task. Employees at a manufacturing company were asked to complete a procedural software task and…

Study on the behaviour of high energy electrons in REPUTE-1 ULQ plasmas

International Nuclear Information System (INIS)

Ogawa, Y.; Morikawa, J.; Nihei, H.; Nakajima, T.; Ozawa, D.; Ohno, M.; Suzuki, T.; Himura, H.; Yoshida, Z.; Morita, S.; Shirai, Y.

2001-01-01

In REPUTE-1 Ultra-Low-q (ULQ) plasmas, behaviors of high energy electrons have been studied through a low-Z pellet injection experiment, in addition to the measurements of soft-X ray PHA and Electron Energy Analyzer (EEA). The high energy tail has been measured in the soft-X ray spectrum, and EEA signal has shown a strong anisotropy of the electron distribution function (i.e., the electron flux to the electron drift side is dominant). To study temporal and spatial information on these high energy electrons, a low-Z pellet injection experiment has been conducted. A small piece of plastic pellet is injected from the top of the REPUTE-1 device, and the trajectory of the pellet inside the plasma is measured by CCD camera. We have observed a large deflection of the pellet trajectory to the toroidal direction opposite to the plasma current (i.e., the electron drift side). This suggests that a pellet is ablated selectively only from one side due to the high energy electrons with a large heat flux. We have calculated the heat flux carried by high energy electrons. Since the repulsion force to the pellet can be calculated with the 2 nd derivative of the pellet trajectory, we have estimated the heat flux of high energy electrons to be a few tens MW/m 2 around the plasma center. Experimental data by EEA measurement and low-Z pellet ablation show the large population of the high energy electrons at the core region in comparison with the edge region, suggesting a MHD dynamo mechanism for the production of the high energy electrons. (author)

Ab Initio Study of Electronic Excitation Effects on SrTiO₃

Energy Technology Data Exchange (ETDEWEB)

Zhao, Shijun [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhang, Yanwen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); Weber, William J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

2017-11-14

Interaction of energetic ions or lasers with solids often induces electronic excitations that may modify material properties significantly. In this study, effects of electronic excitations on strontium titanate SrTiO₃ (STO) are investigated based on first-principles calculations. The lattice structure, electronic properties, lattice vibrational frequencies, and dynamical stabilities are studied in detail. The results suggest that electronic excitation induces charge redistribution that is mainly observed in Ti–O bonds. The electronic band gap increases with increasing electronic excitation, as excitation mainly induces depopulation of Ti 3d states. Phonon analysis indicates that there is a large phonon band gap induced by electronic excitation because of the changes in the vibrational properties of Ti and O atoms. In addition, a new peak appears in the phonon density of states with imaginary frequencies, an indication of lattice instability. Further dynamics simulations confirm that STO undergoes transition to an amorphous structure under strong electronic excitations. In conclusion, the optical properties of STO under electronic excitation are consistent with the evolution of atomic and electronic structures, which suggests a possibility to probe the properties of STO in nonequilibrium state using optical measurement.

Electronic Structure of the Perylene / Zinc Oxide Interface: A Computational Study of Photoinduced Electron Transfer and Impact of Surface Defects

KAUST Repository

Li, Jingrui

2015-07-29

The electronic properties of dye-sensitized semiconductor surfaces consisting of pery- lene chromophores chemisorbed on zinc oxide via different spacer-anchor groups, have been studied at the density-functional-theory level. The energy distributions of the donor states and the rates of photoinduced electron transfer from dye to surface are predicted. We evaluate in particular the impact of saturated versus unsaturated aliphatic spacer groups inserted between the perylene chromophore and the semiconductor as well as the influence of surface defects on the electron-injection rates.

Electronic Structure of the Perylene / Zinc Oxide Interface: A Computational Study of Photoinduced Electron Transfer and Impact of Surface Defects

KAUST Repository

Li, Jingrui; Li, Hong; Winget, Paul; Bredas, Jean-Luc

2015-01-01

The electronic properties of dye-sensitized semiconductor surfaces consisting of pery- lene chromophores chemisorbed on zinc oxide via different spacer-anchor groups, have been studied at the density-functional-theory level. The energy distributions of the donor states and the rates of photoinduced electron transfer from dye to surface are predicted. We evaluate in particular the impact of saturated versus unsaturated aliphatic spacer groups inserted between the perylene chromophore and the semiconductor as well as the influence of surface defects on the electron-injection rates.

Electronic Freight Management Case Studies : a Summary of Results

Science.gov (United States)

2012-04-01

The Electronic Freight Management (EFM) initiative is a USDOT-sponsored project that applies Web technologies that improve data and message transmissions between supply chain partners. The EFM implementation case studies contained in this document ex...

Auger electron spectroscopy studies of boron carbide

International Nuclear Information System (INIS)

Madden, H.H.; Nelson, G.C.; Wallace, W.O.

1986-01-01

Auger electron spectroscopy has been used to probe the electronic structure of ion bombardment (IB) cleaned surfaces of B 9 C and B 4 C samples. The shapes of the B-KVV and C-KVV Auger lines were found to be relatively insensitive to the bulk stoichiometry of the samples. This indicates that the local chemical environments surrounding B and C atoms, respectively, on the surfaces of the IB cleaned samples do not change appreciably in going from B 9 C to B 4 C. Fracturing the sample in situ is a way of producing a clean representative internal surface to compare with the IB surfaces. Microbeam techniques have been used to study a fracture surface of the B 9 C material with greater spatial resolution than in our studies of IB surfaces. The B 9 C fracture surface was not homogeneous and contained both C-rich and B-rich regions. The C-KVV line for the C-rich regions was graphitic in shape. Much of the C-rich regions was found by IB to be less than 100 nm in thickness. The C-KVV line from the B-rich regions was carbidic and did not differ appreciably in shape from those recorded for the IB cleaned surfaces

Electronic structure of a striped nickelate studied by the exact exchange for correlated electrons (EECE) approach

KAUST Repository

Schwingenschlögl, Udo

2009-12-01

Motivated by a RIXS study of Wakimoto, et al.(Phys. Rev. Lett., 102 (2009) 157001) we use density functional theory to analyze the magnetic order in the nickelate La5/3Sr1/3NiO4 and the details of its crystal and electronic structure. We compare the generalized gradient approximation to the hybrid functional approach of exact exchange for correlated electrons (EECE). In contrast to the former, the latter reproduces the insulating state of the compound and the midgap states. The EECE approach, in general, appears to be appropriate for describing stripe phases in systems with orbital degrees of freedom. Copyright © EPLA, 2009.

Born-Oppenheimer Dynamics, Electronic Friction, and the Inclusion of Electron-Electron Interactions

Science.gov (United States)

Dou, Wenjie; Miao, Gaohan; Subotnik, Joseph E.

2017-07-01

We present a universal expression for the electronic friction as felt by a set of classical nuclear degrees of freedom (DOFs) coupled to a manifold of quantum electronic DOFs; no assumptions are made regarding the nature of the electronic Hamiltonian and electron-electron repulsions are allowed. Our derivation is based on a quantum-classical Liouville equation for the coupled electronic-nuclear motion, followed by an adiabatic approximation whereby electronic transitions are assumed to equilibrate faster than nuclear movement. The resulting form of friction is completely general, but does reduce to previously published expressions for the quadratic Hamiltonian (i.e., Hamiltonians without electronic correlation). At equilibrium, the second fluctuation-dissipation theorem is satisfied and the frictional matrix is symmetric. To demonstrate the importance of electron-electron correlation, we study electronic friction within the Anderson-Holstein model, where a proper treatment of electron-electron interactions shows signatures of a Kondo resonance and a mean-field treatment is completely inadequate.

Study of the SEY dependence on the electron beams dose and energy

International Nuclear Information System (INIS)

Commisso, M.

2011-01-01

During operation, the internal walls of modern particle accelerators are subjected to synchrotron radiation irradiation and/or electron bombardment. Such phenomena do affect surface properties such as the secondary electron yield, (SEY). A low SEY is a key parameter to control and overcome any detrimental effect on the accelerator performance eventually induced by the build-up of an Electron Cloud (E C). In laboratory experiments SEY reduction (called scrubbing) has been studied as a function of dose but the actual kinetic energy dependence has never been considered as an important parameter. For this reason and given the peculiar behavior observed for low-energy electrons, we decided to study this dependence accurately. Here we report results of SEY measurements performed bombarding Cu samples obtained from the Large Hadron Collider (Lhc) with different doses of electron beam with energy in the range 10-500 eV. Our results demonstrate that the potentiality of an electron beam to reduce the SEY does not only depend on its dose, but also on its energy. Furthermore, since E C build-up was predicted and observed also the DAΦNE ring, we report some preliminary measurements on the conditioning of Al samples. An overview of future experiments which we will perform in LNF is then given.

Second harmonic electron cyclotron emission studies of Tokapole-II plasmas

International Nuclear Information System (INIS)

Sengstacke, M.A.

1984-03-01

The electron temperature is an important parameter in plasma physics. The intensity of electron cyclotron emission (ECE) is a function of the electron temperature. This function reduces to a direct proportionality for optically thick plasmas. Thus a study of ECE can help us understand various plasma properties. The principal diagnostic used is a radiometer consisting of a microwave superheterodyne receiver operating in the K band, (26.5,40) GHz, and fed by a three inch parabolic mirror with a spot size of about 4.4 cm. The entire microwave assembly can be rotated through 90 0 about the mirror axis to facilitate polarization measurements. A ray tracing analysis of Tokapole-II shows that refraction is significant for plasmas observed in this work

Study of polysilane mainchain electronic structure by picosecond pulse radiolysis

International Nuclear Information System (INIS)

Habara, H.; Saeki, A.; Kunimi, Y.; Seki, S.; Kozawa, T.; Yoshida, Y.; Tagawa, S.

2000-01-01

The electronic structure of a charged polysilane molecle is studied. The transient absorption spectroscopy was carried out for charged radicals of poly (methylphenylsilane): PMPS by pico-second and nanosecond pulse radiolysis technique. It was observed that the peak of the transient absorption spectra shifted to longer wavelength region within a few nsec, and an increase was observed in the optical density at 370 nm, which had been already assigned to the radical anions of PMPS. It is ascribed to inter-segment electron transfer (intra-molecular transfer) through polymer chain. The nanosecond pulse radiolysis experiments gave similar kinetic traces in near-UV and IR region. This suggests the presence of an interband level, that is, a polaron level occupied by an excess electron or a hole. (author)

Studies of electron correlation in the photoionization process

International Nuclear Information System (INIS)

Rosenberg, R.A.

1979-03-01

Electron correlation is a result of the interaction of two or more electrons confined in a region of space, and may conveniently be treated under the formalism of configuration interaction (CI). Photoionization provides a rather direct experimental method for studying CI. The types of CI involved in the photoionization process can be divided into three categories: initial-state configuration interaction (ISCI), final-ionic-state configuration interaction (FISCI), and continuum-state configuration interaction (CSCI). The photoelecton spectroscopy of Ba, Sm, Eu, and Yb was studied using both HeI (22.22 eV) and NeI (16.85 eV) radiation. Satellite structure observed in these spectra using NeI (and for Yb, HeI also) radiation could be satisfactorily explained by ISCI alone. The HeI spectra of Sm, Eu, and, in particular, Ba showed dramatic changes in the satellite population which could only be explained by autoionization, a special form of CSCI. The detailed nature of this mechanism was explored in Ba with synchrotron radiation. It was found that the autoionizing level decays preferentially via an Auger-type mechanism. Further insight into autoionization was gained in the electron impact/ejected electron spectra of Ba (5p 6 6s 2 ) and Yb (5p 6 4f 14 6s 2 ). Autoionizing levels excited above the first (5p) -1 threshold decayed primarily in a two-step Auger process, leading to a relatively large number of doubly charged ions. For autoionizing states below the (5p) -1 limit, decay appears to go to ground and excited states of the singly charged ion. The first experimental determination of the lifetime of the XeII 5s5p 6 2 S/sub 1/2/ state yielded a value of 34.4(6) ns. Reasonable agreement with theory could only be reached by including both FISCI and relativistic effects in calculating the lifetime. 173 references, 43 figures, 10 tables

Study of chemical shifts of the chloroform complexes with cyclic donors of electrons

International Nuclear Information System (INIS)

Blaszkiewicz, B.; Pajak, Z.

1973-01-01

Chemical shifts of chloroform complexes with the heterocyclic electron donors: pyridine, piperidine, alpha-picoline and gamma-picoline have been studied using the high resolution (5.10 -9 ) spectrometer operating at 80 MHz. An attempt has also been made to study the three - component solutions of : chloroform, a heterocyclic donor of electrons and carbon tetrachloride. The results, which have been obtained, indicate that the complex-forming power of pyridine and other electron donors is greater in carbon tetrachloride than in other solvents. (S.B.)

Synthesis and Studies of Sulfur-Containing Heterocyclic Molecules for Molecular Electronics

DEFF Research Database (Denmark)

Mazzanti, Virginia

This work describes the synthesis and studies of sulfur containing π conjugated heterocycles, which are considered interesting motifs in the field of molecular electronics. The first project, which is covered in Chapter 1, concerns the functionalization of tetracycle dibenzo[bc,fg][1,4]dithiapent......This work describes the synthesis and studies of sulfur containing π conjugated heterocycles, which are considered interesting motifs in the field of molecular electronics. The first project, which is covered in Chapter 1, concerns the functionalization of tetracycle dibenzo[bc,fg][1......,4]dithiapentalene (DDP). Attempts to prepare the S-O analog are also discussed. Chapter 2, focuses upon the studies performed on DDP and other sulfur containing π conjugated organic molecules. Organic Field Effect Transistor devices were fabricated and their performances were evaluated. Chapter 3 entails...... the synthesis of dimeric structures of redox active system tetrathiafulvalene (TTF). Molecules with different conjugation pathways bridging two TTFs were synthesized and studied using CV and DPV in order to probe the electronic interaction between these two redox units. The last aspect of this thesis, which...

Electron microscope studies

International Nuclear Information System (INIS)

Crewe, A.V.; Kapp, O.H.

1992-01-01

This is a report covering the research performed in the Crewe laboratory between 1964 and 1992. Because of limitations of space we have provided relatively brief summaries of the major research directions of the facility during these years. A complete bibliography has been included and we have referenced groups of pertinent publications at the beginning of each section. This report summarizes our efforts to develop better electron microscopes and chronicles many of the experimental programs, in materials science and biology, that acted both as a stimulus to better microscope design and also as a testing ground for many instrumental innovations

Electron microscope studies

Energy Technology Data Exchange (ETDEWEB)

Crewe, A.V.; Kapp, O.H.

1992-07-01

This is a report covering the research performed in the Crewe laboratory between 1964 and 1992. Because of limitations of space we have provided relatively brief summaries of the major research directions of the facility during these years. A complete bibliography has been included and we have referenced groups of pertinent publications at the beginning of each section. This report summarizes our efforts to develop better electron microscopes and chronicles many of the experimental programs, in materials science and biology, that acted both as a stimulus to better microscope design and also as a testing ground for many instrumental innovations.

Effective electron-electron and electron-phonon interactions in the Hubbard-Holstein model

International Nuclear Information System (INIS)

Aprea, G.; Di Castro, C.; Grilli, M. . E-mail marco.grilli@roma1.infn.it; Lorenzana, J.

2006-01-01

We investigate the interplay between the electron-electron and the electron-phonon interaction in the Hubbard-Holstein model. We implement the flow-equation method to investigate within this model the effect of correlation on the electron-phonon effective coupling and, conversely, the effect of phonons in the effective electron-electron interaction. Using this technique we obtain analytical momentum-dependent expressions for the effective couplings and we study their behavior for different physical regimes. In agreement with other works on this subject, we find that the electron-electron attraction mediated by phonons in the presence of Hubbard repulsion is peaked at low transferred momenta. The role of the characteristic energies involved is also analyzed

C library for topological study of the electronic charge density.

Science.gov (United States)

Vega, David; Aray, Yosslen; Rodríguez, Jesús

2012-12-05

The topological study of the electronic charge density is useful to obtain information about the kinds of bonds (ionic or covalent) and the atom charges on a molecule or crystal. For this study, it is necessary to calculate, at every space point, the electronic density and its electronic density derivatives values up to second order. In this work, a grid-based method for these calculations is described. The library, implemented for three dimensions, is based on a multidimensional Lagrange interpolation in a regular grid; by differentiating the resulting polynomial, the gradient vector, the Hessian matrix and the Laplacian formulas were obtained for every space point. More complex functions such as the Newton-Raphson method (to find the critical points, where the gradient is null) and the Cash-Karp Runge-Kutta method (used to make the gradient paths) were programmed. As in some crystals, the unit cell has angles different from 90°, the described library includes linear transformations to correct the gradient and Hessian when the grid is distorted (inclined). Functions were also developed to handle grid containing files (grd from DMol® program, CUBE from Gaussian® program and CHGCAR from VASP® program). Each one of these files contains the data for a molecular or crystal electronic property (such as charge density, spin density, electrostatic potential, and others) in a three-dimensional (3D) grid. The library can be adapted to make the topological study in any regular 3D grid by modifying the code of these functions. Copyright © 2012 Wiley Periodicals, Inc.

Transmission Electron Microscopy Studies of Electron-Selective Titanium Oxide Contacts in Silicon Solar Cells

KAUST Repository

Ali, Haider

2017-08-15

In this study, the cross-section of electron-selective titanium oxide (TiO2) contacts for n-type crystalline silicon solar cells were investigated by transmission electron microscopy. It was revealed that the excellent cell efficiency of 21.6% obtained on n-type cells, featuring SiO2/TiO2/Al rear contacts and after forming gas annealing (FGA) at 350°C, is due to strong surface passivation of SiO2/TiO2 stack as well as low contact resistivity at the Si/SiO2/TiO2 heterojunction. This can be attributed to the transformation of amorphous TiO2 to a conducting TiO2-x phase. Conversely, the low efficiency (9.8%) obtained on cells featuring an a-Si:H/TiO2/Al rear contact is due to severe degradation of passivation of the a-Si:H upon FGA.

Postponed variety creation: case study in consumer electronics retail

DEFF Research Database (Denmark)

Appelqvist, Patrik; Gubi, Ebbe

2004-01-01

Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design/methodology/approach – Improve......Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design...... is beneficial in retail. Findings – In the case company, shop inventory is necessary for high-volume and low-variety products. Postponing variety creation to shops has the potential to decrease inventories for these products by 40-80 per cent. The benefits of postponement depend on delivery speed requirement......, product value, product variety and shop size. Research limitations/implications – Many contributions on postponement have been conceptual. This study contains a quantitative test. The study considers both the spatial dimension (where) and the temporal dimension (when) of postponement. Practical...

Postponed variety creation: case study in consumer electronics retail

DEFF Research Database (Denmark)

Appelqvist, Patrik; Gubi, Ebbe

2005-01-01

Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design/methodology/approach – Improve......Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design...... is beneficial in retail. Findings – In the case company, shop inventory is necessary for high-volume and low-variety products. Postponing variety creation to shops has the potential to decrease inventories for these products by 40-80 per cent. The benefits of postponement depend on delivery speed requirement......, product value, product variety and shop size. Research limitations/implications – Many contributions on postponement have been conceptual. This study contains a quantitative test. The study considers both the spatial dimension (where) and the temporal dimension (when) of postponement. Practical...

Electron impact study of potassium hydroxide

Science.gov (United States)

Vuskovic, L.; Trajmar, S.

1979-01-01

An attempt is made to measure the sum of the elastic, rotational and vibrational scattering of electrons by KOH at low impact energies (5 to 20 eV) at angles from 10 to 120 deg. Energy loss spectra taken in the 0 to 18 eV range using an electron impact spectrometer are used to identify the species contributing to electric scattering. At temperatures between 300 and 500 C, only inelastic spectral features belonging to water are detected, while at temperatures from 500 to 800 C strong atomic K lines, indicative of molecular dissociation, and H2 energy loss features become prominent. No features attributable to KOH, the KOH dimer, O2 or potassium oxides were observed, due to the effects of the dissociation products, and it is concluded that another technique will have to be developed in order to measure electron scattering by KOH.

Studies of instabilities and waves in a mirror confined hot electron plasma

International Nuclear Information System (INIS)

Huang Chaosong; Qiu Lijian; Ren Zhaoxing

1989-01-01

The stability of hot electron plasmas is studied. The hot electron component can stabilize the low frequency drift wave and the interchange mode driven by the plasma, which depends only on α=N h /N i , the density ratio of the hot electrons to the plasma ions, but not on the beta value and the annular structure of the hot electrons. Stabilization of the drift wave occurs for α > 40%, and that of the interchange mode for α > 5%, which allows the prediction that the interchange mode can be suppressed in hot electron plasma experiments. The experiments have been conducted in a simple mirror machine. It is observed that the plasma drives a drift wave at 40 kHz and an interchange mode at about 100 kHz. The fluctuation amplitude of the drift wave is much higher than that of the interchange mode. The hot electrons reduce the density gradient, the fluctuation amplitude and the radial loss of the plasma. On the other hand, the hot electrons drive the interchange mode and drift wave in the ion cyclotron frequency region. The effects of a cold plasma on hot electron perturbations are discussed. (author). 10 refs, 6 figs

Phenomenological studies of electron-beam transport in wire-plasma channels

International Nuclear Information System (INIS)

Lockwood, G.J.; Beezhold, W.

1980-01-01

Multiple electron-beam transport in air through plasma channels is an important method for delivering many intense beams to a bremsstrahlung converter system. This paper reports work intended to optimize this transport technique with emphasis on transport through curved channels and on transport efficiencies. Curved-channel transport allows accelerators such as Sandia's PROTO II and PBFA I facilities to be used as flash x-ray sources for weapon effects simulation without reconfiguring the diodes or developing advanced converters. The formation mechanisms of wire-initiated plasma channels in air were examined and the subsequent transport efficiencies of relativistic electron beams through various-length straight and curved plasma channels were determined. Electron transport efficiency through a channel was measured to be 80 to 100% of a zero length channel for 40 cm long straight channels and for curved channels which re-directed the electron beam through an angle of 90 0 . Studies of simultaneous e-beam transport along two curved channels closely spaced at the converter showed that transport efficiency remained at 80 to 100%. However, it was observed that the two e-beams were displaced towards each other. Transport efficiency was observed to depend only weakly on parameters such as wire material, wire length and shape, diode anode aperture, e-beam injection time, and wire-channel applied voltage. For off-center injection conditions the electron beam strongly perturbed the plasma channel in periodic or regularly spaced patterns even though the total energy lost by the electron beam remained small. Plasma-channel transport, when all experimental parameters have been optimized for maximum transport efficiency, is a workable method for directing electron beams to a converter target

Study of diffused particles by an electron cyclotron-resonance ions source plasma

International Nuclear Information System (INIS)

Klein, J.P.

1995-01-01

A double electrostatic analyser has been built mainly to study the loss cone electron population. The analysis of the ions can help to determine the plasma potential. The possibility of applying two analysing potentials along the extraction decaying magnetic filed allowed us to determine the anisotropy of the electron distribution function, of parallel temperature Tpar and perpendicular temperature Tper outside the plasma. The Tpar temperature remains constant at around 10 eV when Tper increases from 30 eV to 150 eV with improved confinement. The electron cyclotron heating provides mainly perpendicular energy to the electrons. The perpendicular electron energy is then converted to parallel energy predominantly by electron ion collisions and leave the plasma with a frequency depending on v per -3 . Taking a Maxwellian function of temperature T per cent to describe the electron function distribution f cent (v per ) in the center of the plasma is in line with the experimental electron characteristics obtained with a single electrostatic potential. Temperatures of 2 keV have been reached at 10 Ghz and 6 keV at 18 Ggz. Measurements of density and diamagnetism can complete the description of this warm population: the warm electrons dominate in number but leave the plasma quicker than the very hot electron population (analysed with the X ray diagnostic). For this reason the energy density of warm electrons is less than that of the very hot population by warm electrons consume most of the injected rf power. (author). 52 refs., 100 figs

Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

Directory of Open Access Journals (Sweden)

J Emami

2010-09-01

Full Text Available "nBackground and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated. "nMethods: The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE, and mean dissolution time (MDT was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT or fraction of the drug dissolved (FRD vs fraction of the drug absorbed (FRA. "nResults: Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50 did not reflect their in vivo properties. Major conclusions: Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in

Study of runaway electron generation during major disruptions in JET

International Nuclear Information System (INIS)

Plyusnin, V.V.; Riccardo, V.; Jaspers, R.; Alper, B.; Kiptily, V.G.; Mlynar, J.; Popovichev, S.; Luna, E. de La; Andersson, F.

2006-01-01

Extensive analysis of disruptions in JET has helped advance the understanding of trends of disruption-generated runaway electrons. Tomographic reconstruction of the soft x-ray emission has made possible a detailed observation of the magnetic flux geometry evolution during disruptions. With the aid of soft and hard x-ray diagnostics runaway electrons have been detected at the very beginning of disruptions. A study of runaway electron parameters has shown that an approximate upper bound for the conversion efficiency of pre-disruptive plasma currents into runaways is about 60% over a wide range of plasma currents in JET. Runaway generation has been simulated with a test particle model in order to verify the results of experimental data analysis and to obtain the background for extrapolation of the existing results onto larger devices such as ITER. It was found that close agreement between the modelling results and experimental data could be achieved if in the calculations the post-disruption plasma electron temperature was assumed equal to 10 eV and if the plasma column geometry evolution is taken into account in calculations. The experimental trends and numerical simulations show that runaway electrons are a critical issue for ITER and, therefore, the development of mitigation methods, which suppress runaway generation, is an essential task

Postponed variety creation: case study in consumer electronics retail

DEFF Research Database (Denmark)

Appelqvist, Patrik; Gubi, Ebbe

2005-01-01

Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design/methodology/approach – Improve...... modular product architecture can be utilised to improve operational supply chain performance.......Purpose – Postponement is known as a way to reduce risk and inventories while still providing high product variety and acceptable response times. The paper is a case study that uses simulation for quantifying these benefits for a consumer electronics company. Design....../methodology/approach – Improvement potential is first evaluated qualitatively through interviews with dealers of the case company. Next, the benefit of postponement is evaluated quantitatively using discrete-event simulation with data from operational ERP systems. The conclusions identify conditions under which postponement...

Electron paramagnetic resonance study on n-type electron-irradiated 3C-SiC

Energy Technology Data Exchange (ETDEWEB)

Carlsson, P; Rabia, K; Son, N T; Janzen, E [Department of Physics, Chemistry and Biology, Linkoeping University, SE-581 83 Linkoeping (Sweden); Ohshima, T; Morishita, N; Itoh, H [Japan Atomic Energy Research Institute, Takasaki 370-1292 (Japan); Isoya, J [University of Tsukuba, Tsukuba 305-8550 (Japan)], E-mail: paca@ifm.liu.se

2008-03-15

Electron Paramagnetic Resonance (EPR) was used to study defects in n-type 3C-SiC films irradiated by 3-MeV electrons at room temperature with a dose of 2x10{sup 18} cm{sup -2}. After electron irradiation, two new EPR spectra with an effective spin S = 1, labeled L5 and L6, were observed. The L5 center has C{sub 3v} symmetry with g = 2.004 and a fine-structure parameter D = 436.5x10{sup -4} cm{sup -1}. The L5 spectrum was only detected under light illumination and it could not be detected after annealing at {approx}550{sup 0}C. The principal z-axis of the D tensor is parallel to the <111>-directions, indicating the location of spins along the Si-C bonds. Judging from the symmetry and the fact that the signal was detected under illumination in n-type material, the L5 center may be related to the divacancy in the neutral charge state. The L6 center has a C{sub 2v}-symmetry with an isotropic g-value of g = 2.003 and the fine structure parameters D = 547.7x10{sup -4} cm{sup -1} and E = 56.2x10{sup -4} cm{sup -1}. The L6 center disappeared after annealing at a rather low temperature ({approx}200 deg. C), which is substantially lower than the known annealing temperatures for vacancy-related defects in 3C-SiC. This highly mobile defect may be related to carbon interstitials.

In Situ Transmission Electron Microscopy Study of Electron Beam-Induced Transformations in Colloidal Cesium Lead Halide Perovskite Nanocrystals

Science.gov (United States)

2017-01-01

An increasing number of studies have recently reported the rapid degradation of hybrid and all-inorganic lead halide perovskite nanocrystals under electron beam irradiation in the transmission electron microscope, with the formation of nanometer size, high contrast particles. The nature of these nanoparticles and the involved transformations in the perovskite nanocrystals are still a matter of debate. Herein, we have studied the effects of high energy (80/200 keV) electron irradiation on colloidal cesium lead bromide (CsPbBr3) nanocrystals with different shapes and sizes, especially 3 nm thick nanosheets, a morphology that facilitated the analysis of the various ongoing processes. Our results show that the CsPbBr3 nanocrystals undergo a radiolysis process, with electron stimulated desorption of a fraction of bromine atoms and the reduction of a fraction of Pb2+ ions to Pb0. Subsequently Pb0 atoms diffuse and aggregate, giving rise to the high contrast particles, as previously reported by various groups. The diffusion is facilitated by both high temperature and electron beam irradiation. The early stage Pb nanoparticles are epitaxially bound to the parent CsPbBr3 lattice, and evolve into nonepitaxially bound Pb crystals upon further irradiation, leading to local amorphization and consequent dismantling of the CsPbBr3 lattice. The comparison among CsPbBr3 nanocrystals with various shapes and sizes evidences that the damage is particularly pronounced at the corners and edges of the surface, due to a lower diffusion barrier for Pb0 on the surface than inside the crystal and the presence of a larger fraction of under-coordinated atoms. PMID:28122188

Optical studies of MBE-grown InN nanocolumns: Evidence of surface electron accumulation

Science.gov (United States)

Segura-Ruiz, J.; Garro, N.; Cantarero, A.; Denker, C.; Malindretos, J.; Rizzi, A.

2009-03-01

Vertically self-aligned InN nanocolumns have been investigated by means of scanning electron microscopy, Raman scattering, and photoluminescence spectroscopy. Different nanocolumn morphologies corresponding to different molecular beam epitaxy growth conditions have been studied. Raman spectra revealed strain-free nanocolumns with high crystalline quality for the full set of samples studied. Longitudinal optical modes both uncoupled and coupled to an electron plasma coexist in the Raman spectra pointing to the existence of two distinctive regions in the nanocolumn: a surface layer of degenerated electrons and a nondegenerated inner core. The characteristics of the low-temperature photoluminescence and its dependence on temperature and excitation power can be explained by a model considering localized holes recombining with degenerated electrons close to the nonpolar surface. The differences observed in the optical response of different samples showing similar crystalline quality have been attributed to the variation in the electron accumulation layer with the growth conditions.

Limitations in accurate electron density studies

International Nuclear Information System (INIS)

Wal, R. van der.

1982-01-01

Most of X-ray diffraction studies are devoted to the determination of three-dimensional crystal structures from the electron density distributions. In these cases the density distributions are described by the independent atom model (IAM model), which consists of a superposition of spherically averaged free atom densities, which are smeared by thermal vibrations. During the last few decades studies have been made into the deviations of the density distribution from the IAM model, which enables a study of the chemical binding between atoms. The total density can be described using pseudo-atom multipole models as a superposition of aspherical pseudo-atom densities. A fundamental problem is that the separation of this density into an IAM and a deformation part is not unique. This thesis considers the problem and besides deformation densities from X-ray diffraction also considers the corresponding deformation electric field and deformation potential. (C.F.)

New possibilities for using laser polarimetry technology to study electron paramagnetic resonance

Energy Technology Data Exchange (ETDEWEB)

Aleksandrov, E V; Zapasskii, V S

1982-01-01

Optical methods of recording electron paramagnetic resonance which arose in the early 50's as applied to the problem of recording the magnetic resonance of excited atoms is at the present time widely used in studying the electron paramagnetic resonance of the ground and excited states of free atoms and paramagnetic centers in condensed media. At the present time attention is devoted to the additional possibilities of optical methods of electron paramagnetic resonance which are realized using laser sources.

Positron lifetime study of electron-irradiated epoxy resins

International Nuclear Information System (INIS)

Suevegh, K.; Vertes, A.; Wojnarovits, L.; Foeldiak, G.; Liszkai, L.; Kajcsos, Zs.

1990-01-01

Two bisphenol-A type epoxy resins were irradiated by electron beam and studied afterwards by positron lifetime spectroscopy. An interesting result is that despite of the considerable amount of free-radicals, no inhibition of positronium formation was observed in the two epoxies. Nevertheless, several serious differences were detected between the studied polymers. The results suggest that the radiation-resistant properties of epoxies depend strongly on the amount of the curing agent. (author) 8 refs.; 2 figs

Transport studies of LPA electron beam towards the FEL amplification at COXINEL

Energy Technology Data Exchange (ETDEWEB)

Khojoyan, M., E-mail: martin.khojoyan@synchrotron-soleil.fr; Briquez, F.; Labat, M.; Loulergue, A.; Marcouillé, O.; Marteau, F.; Sharma, G.; Couprie, M.E.

2016-09-01

Laser Plasma Acceleration (LPA) [1] is an emerging concept enabling to generate electron beams with high energy, high peak current and small transverse emittance within a very short distance. The use of LPA can be applied to the Free Electron Laser (FEL) [2] case in order to investigate whether it is suitable for the light amplification in the undulator. However, capturing and guiding of such beams to the undulator is very challenging, because of the large divergence and high energy spread of the electron beams at the plasma exit, leading to large chromatic emittances. A specific beam manipulation scheme was recently proposed for the COXINEL (Coherent X-ray source inferred from electrons accelerated by laser) setup, which makes an advantage from the intrinsically large chromatic emittance of such beams [3]. The electron beam transport is studied using two simulation codes: a SOLEIL in-house one and ASTRA [4]. The influence of the collective effects on the electron beam performance is also examined.

Atomic and molecular photoelectron and Auger-electron-spectroscopy studies using synchrotron radiation

International Nuclear Information System (INIS)

Southworth, S.H.

1982-01-01

Electron spectroscopy, combined with synchrotron radiation, was used to measure the angular distributions of photoelectrons and Auger electrons from atoms and molecules as functions of photon energy. The branching ratios and partial cross sections were also measured in certain cases. By comparison with theoretical calculations, the experimental results are interpreted in terms of the characteristic electronic structure and ionization dynamics of the atomic or molecular sample. The time structure of the synchrotron radiation source was used to record time-of-flight (TOF) spectra of the ejected electrons. The double-angle-TOF method for the measurement of photoelectron angular distributions is discussed. This technique offers the advantages of increased electron collection efficiency and the elimination of certain systematic errors. An electron spectroscopy study of inner-shell photoexcitation and ionization of Xe, photoelectron angular distributions from H 2 and D 2 , and photoionization cross sections and photoelectron asymmetries of the valence orbitals of NO are reported

Electron and impurity transport studies in the TCV Tokamak

Energy Technology Data Exchange (ETDEWEB)

Wagner, D.

2013-05-15

In this thesis electron and impurity transport are studied in the Tokamak à Configuration Variable (TCV) located at CRPP-EPFL in Lausanne. Understanding particle transport is primordial for future nuclear fusion power plants. Modeling of experiments in many specific plasma scenarios can help to understand the common elements of the physics at play and to interpret apparently contradictory experiments on the same machine and across different machines. The first part of this thesis deals with electron transport in TCV high confinement mode plasmas. It was observed that the electron density profile in these plasmas flatten when intense electron heating is applied, in contrast to observations on other machines where the increase of the profile peakedness was reported. It is shown with quasi-linear gyrokinetic simulations that this effect, usually interpreted as collisionality dependence, stems from the combined effect of many plasma parameters. The influence of the collisionality, electron to ion temperature ratio, the ratio of temperature gradients, and the Ware-pinch are studied with detailed parameter scans. It is shown that the complex interdependence of the various plasma parameters is greatly simplified when the simulation results are interpreted as a function of the average frequency of the main modes contributing to radial transport. In this way the model is able to explain the experimental results. It was also shown that the same basic understanding is at play in L-modes, H-modes and electron internal transport barriers. The second part of the thesis is devoted to impurity transport. A multi-purpose gas injection system is developed, commissioned and calibrated. It is shown that the system is capable of massive gas injections to provoke disruptions and delivering small puffs of gaseous impurities for perturbative transport experiments. This flexible tool is exploited in a series of impurity transport measurements with argon and neon injections. The impurities

Electron and impurity transport studies in the TCV Tokamak

International Nuclear Information System (INIS)

Wagner, D.

2013-05-01

In this thesis electron and impurity transport are studied in the Tokamak à Configuration Variable (TCV) located at CRPP-EPFL in Lausanne. Understanding particle transport is primordial for future nuclear fusion power plants. Modeling of experiments in many specific plasma scenarios can help to understand the common elements of the physics at play and to interpret apparently contradictory experiments on the same machine and across different machines. The first part of this thesis deals with electron transport in TCV high confinement mode plasmas. It was observed that the electron density profile in these plasmas flatten when intense electron heating is applied, in contrast to observations on other machines where the increase of the profile peakedness was reported. It is shown with quasi-linear gyrokinetic simulations that this effect, usually interpreted as collisionality dependence, stems from the combined effect of many plasma parameters. The influence of the collisionality, electron to ion temperature ratio, the ratio of temperature gradients, and the Ware-pinch are studied with detailed parameter scans. It is shown that the complex interdependence of the various plasma parameters is greatly simplified when the simulation results are interpreted as a function of the average frequency of the main modes contributing to radial transport. In this way the model is able to explain the experimental results. It was also shown that the same basic understanding is at play in L-modes, H-modes and electron internal transport barriers. The second part of the thesis is devoted to impurity transport. A multi-purpose gas injection system is developed, commissioned and calibrated. It is shown that the system is capable of massive gas injections to provoke disruptions and delivering small puffs of gaseous impurities for perturbative transport experiments. This flexible tool is exploited in a series of impurity transport measurements with argon and neon injections. The impurities

Electron-impact study of PO2 using the R-matrix method

Science.gov (United States)

Bharadvaja, Anand; Kaur, Savinder; Baluja, K. L.

2013-06-01

The R-matrix approach is used to study the electron scattering from PO2 radical at low electron impact energies. The elastic scattering phenomenon is studied in static-exchange, one-state and many-states close-coupling approximation. The elastic differential cross sections, corresponding momentum-transfer cross sections, and collision frequency are calculated in the one-state configuration interaction approximation only. Calculations reveal a stable bound state of PO2- having symmetry 1A1, a configuration of ⋯8a12,⋯2b12,⋯5b22,⋯1a22, and vertical electron affinity of 2.94 eV. The excited state of anion PO2- having symmetry 3B1 is also just bound relative to the ground state of PO2 at its equilibrium geometry. The shape, core-excited, and Feshbach resonances are analyzed in different symmetries up to 7 eV. The partial waves up to l=4 are used to represent continuum electron. The converged cross sections are obtained for the partial waves having l greater than 4 by applying Born correction. Certain interesting spectroscopic properties of radical are also reported.

Electronic properties of diphenyl-s-tetrazine and some related oligomers. An spectroscopic and theoretical study

International Nuclear Information System (INIS)

Moral, Mónica; García, Gregorio; Peñas, Antonio; Garzón, Andrés; Granadino-Roldán, José M.; Melguizo, Manuel; Fernández-Gómez, Manuel

2012-01-01

Highlights: ► We study properties of Ph 2 Tz and (PhTz) n Ph as candidates for organic electronics. ► The synthesis of Ph 2 Tz was performed through a modified Pinner-type reaction. ► IR/Raman spectra allowed to conclude that Ph 2 Tz is nearly planar in liquid phase. ► Electronic structure was studied by UV–Vis/TD-DFT methods in different solvents. ► Bandgap, E LUMO , electron mobility predict some n-type character for limit polymer. -- Abstract: This work presents a theoretical and spectroscopic study on the electronic and structural properties of the diphenyl-s-tetrazine molecule (Ph 2 Tz) and some oligomeric derivatives. Ph 2 Tz was synthesized through a variation of Pinner-type reaction which uses N-acetylcysteine as catalyst. Insight into the structure and electronic properties of the title compound was obtained through IR, Raman, UV–Vis spectra in different solvents, and theoretical calculations. Theoretical studies have been extended to different n-mers derivatives up to an ideal molecular wire through the oligomeric approximation, predicting this way electronic properties such as LUMO energy levels, electron affinity and reorganization energy in order to assess their possible applications in molecular electronics.

Study of porous silicon morphologies for electron transport

International Nuclear Information System (INIS)

Pang, Y.; Demroff, H.P.; Elliott, T.S.; Lee, B.; Lu, J.; Madduri, V.B.; Mazumdar, T.K.; McIntyre, P.M.; Smith, D.D.; Trost, H.J.

1993-01-01

Field emitter devices are being developed for the gigatron, a high-efficiency, high frequency and high power microwave source. One approach being investigated is porous silicon, where a dense matrix of nanoscopic pores are galvanically etched into a silicon surface. In the present paper pore morphologies were used to characterize these materials. Using of Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) images of both N-type and P-type porous layers, it is found that pores propagate along the crystallographic direction, perpendicular to the surface of (100) silicon. Distinct morphologies were observed systematically near the surface, in the main bulk and near the bottom of N-type (100) silicon lift-off samples. It is seen that the pores are not cylindrical but exhibit more or less approximately square cross sections. X-ray diffraction spectra and electron diffraction patterns verified that bulk porous silicon is still a single crystal. In addition, a Scanning Tunnelling Microscope (STM) and an Atomic Force Microscope (AFM) were successfully applied to image the 40 angstrom gold film structure which was coated upon a cooled porous silicon layer. By associating the morphology study with the measured emitting current density of the Oxidized Porous Silicon Field Emission Triode (OPSFET), techniques for the surface treatment of porous silicon will be optimized

2001 Industry Studies: Electronics

Science.gov (United States)

2001-01-01

Center, Dallas, TX Northrop Grumman Corp, Electronic Sensors & Systems, Baltimore, MD International Acer Incorporated, Hsin Chu, Taiwan Aerospace...manufacturing. Many of the large-scale fabrication foundries are offshore in such countries as Taiwan, Singapore and Malaysia .5 - 5 - The largest market for...done in the US. However, more of the actual mass manufacturing of the chips are done in Taiwan, Singapore, and Malaysia . A new semiconductor facility

Studies on the dose distribution and treatment technique of high energy electron beams

International Nuclear Information System (INIS)

Lee, D.H.; Chu, S.S.

1978-01-01

Some important properties of high energy electron beams from the linear accelerator, LMR-13, installed in the Yonsei Cancer Center were studied. The results of experimental studies on the problems associated with the 8, 10, and 12 MeV electron beam therapy were as followings; The ionization type dosemeters calibrated by 90 Sr standard source were suitable to the measurements of the outputs and the obsorbed doses in accuracy point of view, and dose measurements using ionization chambers were difficult when measuring doses in small field size and the regions of rapid fall off. The electron energies were measured precisely with an energy spectrometer, and the practical electron energy was calculated within 5% error in the maximum range of the high energy electron beam in water. The correcting factors of perturbated dose distributions owing to radiation field, energy, and materials of the treatment cone were checked and described systematically and thus the variation of dose distributions due to the non-homogeneities of tissues and slopping skin surfaces were completely compensated. The electron beams were adequately diffused using the scatterers, and minimized the bremsstrahlung, irradiation field size, and materials of scatterers. Thus, the therapeutic capacity with the limited electron energy could be extended by improving the dose distributions. (author)

Experimental study of intensive electron beam scattering in melting channel

International Nuclear Information System (INIS)

Balagura, V.S.; Kurilko, V.I.; Safronov, B.G.

1988-01-01

Multiple scattering of an intensive electron beam at 28 keV energy passing through a melting channel in iron targets is experimentally studied. The dependence of scattering on the melting current value is established. The material density in the channel on the basis of the binary collision method is evaluated. It is shown that these density values are of three orders less than the estimations made on the basis of the data on energy losses of electrons in the channel. 6 refs.; 4 figs

Study of electron recombination in liquid argon with the ICARUS TPC

International Nuclear Information System (INIS)

Amoruso, S.; Antonello, M.; Aprili, P.; Arneodo, F.; Badertscher, A.; Baiboussinov, B.; Baldo Ceolin, M.; Battistoni, G.; Bekman, B.; Benetti, P.; Bischofberger, M.; Borio di Tigliole, A.; Brunetti, R.; Bruzzese, R.; Bueno, A.; Buzzanca, M.; Calligarich, E.; Campanelli, M.; Carbonara, F.; Carpanese, C.; Cavalli, D.; Cavanna, F.; Cennini, P.; Centro, S.; Cesana, A.; Chen, C.; Chen, D.; Chen, D.B.; Chen, Y.; Cieslik, K.; Cline, D.; Cocco, A.G.; Dai, Z.; De Vecchi, C.; Dabrowska, A.; Di Cicco, A.; Dolfini, R.; Ereditato, A.; Felcini, M.; Ferrari, A.; Ferri, F.; Fiorillo, G.; Galli, S.; Ge, Y.; Gibin, D.; Gigli Berzolari, A.; Gil-Botella, I.; Graczyk, K.; Grandi, L.; Guglielmi, A.; He, K.; Holeczek, J.; Huang, X.; Juszczak, C.; Kielczewska, D.; Kisiel, J.; Kozlowski, T.; Laffranchi, M.; Lagoda, J.; Li, Z.; Lu, F.; Ma, J.; Mangano, G.; Markiewicz, M.; Martinez de la Ossa, A.; Matthey, C.; Mauri, F.; Meng, G.; Messina, M.; Montanari, C.; Muraro, S.; Navas-Concha, S.; Otwinowski, S.; Ouyang, Q.; Palamara, O.; Pascoli, D.; Periale, L.; Piano Mortari, G.B.; Piazzoli, A.; Picchi, P.; Pietropaolo, F.; Polopek, W.; Rancati, T.; Rappoldi, A.; Raselli, G.L.; Rico, J.; Rondio, E.; Rossella, M.; Rubbia, A.; Rubbia, C.; Sala, P.R.; Santorelli, R.; Scannicchio, D.; Segreto, E.; Seo, Y.; Sergiampietri, F.; Sobczyk, J.; Spinelli, N.; Stepaniak, J.; Sulej, R.; Szarska, M.; Szeptycka, M.; Terrani, M.; Velotta, R.; Ventura, S.; Vignoli, C.; Wang, H.; Wang, X.; Woo, J.; Xu, G.; Xu, Z.; Zalewska, A.; Zhang, C.; Zhang, Q.; Zhen, S.; Zipper, W.

2004-01-01

Electron recombination in liquid argon (LAr) is studied by means of charged particle tracks collected in various ICARUS liquid argon TPC prototypes. The dependence of the recombination on the particle stopping power has been fitted with a Birks functional dependence. The simulation of the process of electron recombination in Monte Carlo calculations is discussed. A quantitative comparison with previously published data is carried out

Study on discrete space charge effects in electron beams and guns

International Nuclear Information System (INIS)

Tang Tiantong

1990-01-01

The discrete space charge effects in electron beams are studied and a statistical dynamics equation of the ensemble of beam electrons is derived. An approximated analytical solution of this equation is given. This equation has been applied to beam crossover and field-emission and thermal-emission gun problems. The computer calculation results agree on the whole with those of Monte Carlo simulation and experimental data. (orig.)

Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers.

Science.gov (United States)

Burns, Olivia; Zhu, John; Manyak, Michael J; Ravindranath, Ramiya; Koosha, Fariba; Haque, Nazneen; Chung, Sally

2018-05-01

The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed-dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5-mg capsule [Avodart ® ] + 1 tamsulosin hydrochloride 0.2-mg orally disintegrating tablet [Harnal D ® ]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open-label, randomized, single-dose, crossover studies in healthy male adults aged 18-65 years. Trial 1 evaluated 2 formulations (FDC1 and FDC2), and trial 2 evaluated a third formulation (FDC3). The primary end points were dutasteride area under the concentration-time curve from time 0 to t (AUC (0-t) ) and peak plasma concentration (C max ) and tamsulosin AUC (0-∞) , AUC (0-t) , and C max . The formulations were considered to be bioequivalent if the 90%CIs for the geometric mean ratios for each end point were within the range of 0.80-1.25. For FDC1 in trial 1, bioequivalence criteria were not met for dutasteride C max or AUC in the fasted state or for tamsulosin C max in the fasted or fed states. For FDC2 in trial 1, all bioequivalence criteria were met except for tamsulosin C max in the fasted state. For FDC3 in trial 2, bioequivalence criteria were met for all dutasteride and tamsulosin end points in both the fed and fasted states. Safety profiles were similar for all FDC formulations and combination treatments. © 2017, The American College of Clinical Pharmacology.

High-pressure electron-resonance studies of electronic, magnetic, and structural phase transitions. Progress report

International Nuclear Information System (INIS)

Pifer, J.H.; Croft, M.C.

1983-01-01

Research is described in development of a high-pressure electron-resonance probe capable of operating down to 1.5 0 K temperatures. The apparatus has been used to measure the EPR of a sample of DPPH at room temperature and zero pressure. EPR has been used to measure valence field instabilities in alloy systems. Studies have been done on metal-insulator transitions at high pressure, and are briefly described

Solvation of the electron in alcohols studied using the Argonne picosecond pulse radiolysis system

International Nuclear Information System (INIS)

Jonah, C.D.; Kenney-Wallace, G.A.

1979-01-01

With a stroboscopic pulse radiolysis system, it is possible to measure the reactions of solvated electrons and dry electrons and the solvation time of electrons in alcohols from 20 psec to 350 psec. The solvation in alcohol and alcohol-alkane solutions is a complex process which depends on the microscopic structure of the fluid, so that the studies of solvation in alcohols as a function of temperature or as a function of the concentration of the alcohols must take into account the structure of the fluid being studied. The relaxation processes may not be dominant at low temperature. However, in room temperature alcohols, pre-existing traps are the dominant means of electron trapping. The extrapolation to water may be reasonable since water and alcohols both give similar final species. To obtain such idea of the solvation process in alcohols, the change of the absorption of electrons at 500 nm was measured. At very low concentration of alcohols in alkanes, electrons form a complex with a cluster of alcohol molecules, and the most probable size of this cluster is two alcohols (C 4 , C 10 ). The species formed is not solvated electrons, since the characteristic spectrum of solvated electrons is absent, and the conductivity of the species is far above that of solvated electrons. (Yamashita, S.)

ELECTRONIC RETAILING IN MACEDONIA-CASE STUDY OF OHRID REGION

Directory of Open Access Journals (Sweden)

MARGARITA JANESKA

2017-04-01

Full Text Available With electronic retailing that offers the possibility of direct sales, is no longer need expensive business premises, or paying high rents, or employing a number of vendors. There is also the possibility of selling to final consumers in any geographical region in different countries of the world by establishing instant communication, through presenting an interactive multimedia catalog that can offer numerous information то the customers. However, on the other hand, sales through the Internet can appear certain problems. Many potential buyers in the world still do not use the Internet, others don't have fast connections, others do not speak good English, also it requires the existence of trust between both parties, buyer and seller, as well as security in the execution of transactions. The aim of this paper is to treat electronic retailing in Macedonia which is becoming more popular as worldwide, especially in developed parts of the world like the US and Europe. Macedonian companies are increasingly applying electronic method of sale and communication with customers. The number of Internet users and on-line purchase is rapidly expanding what undoubtedly indicates that there is potential for advancement in this field. Also in this paper will be presented a case study where will be analyzed the current state for development of electronic retailing in Macedonia, especially region of Ohrid.

Study of Electron Transport and Amplification in Diamond

Energy Technology Data Exchange (ETDEWEB)

Ben-Zvi, Ilan [Stony Brook Univ., NY (United States); Muller, Erik [Stony Brook Univ., NY (United States)

2015-01-05

The development of the Diamond Amplified Photocathode (DAP) has produced significant results under our previous HEP funded efforts both on the fabrication of working devices and the understanding of the underlying physics governing its performance. The results presented here substantiate the use of diamond as both a secondary electron amplifier for high-brightness, high-average-current electron sources and as a photon and particle detector in harsh radiation environments. Very high average current densities (>10A/cm2) have been transported through diamond material. The transport has been measured as a function of incident photon energy and found to be in good agreement with theoretical models. Measurements of the charge transport for photon energies near the carbon K-edge (290 eV for sp3 bonded carbon) have provided insight into carrier loss due to diffusion; modeling of this aspect of charge transport is underway. The response of diamond to nanosecond x-ray pulses has been measured; in this regime the charge transport is as expected. Electron emission from hydrogenated diamond has been measured using both electron and x-ray generated carriers; a gain of 178 has been observed for electron-generated carriers. The energy spectrum of the emitted electrons has been measured, providing insight into the electron affinity and ultimately the thermal emittance. The origin of charge trapping in diamond has been investigated for both bulk and surface trapping

A comparative bioavailability study of two formulations of pregabalin in healthy Chilean volunteers.

Science.gov (United States)

Quiñones, Luis; Sasso, Jaime; Tamayo, Evelyn; Catalán, Johanna; González, Juan Paplo; Escala, Mario; Varela, Nelson; León, Jorge; Cáceres, Dante Daniel; Saavedra, Iván

2010-07-01

The aim of this study was to compare the pharmacokinetic parameters between two brands of pregabalin in healthy Chilean volunteers. A randomized, single-dose, two-period, two-sequence, crossover study design with a 2-week washout period was conducted in healthy Chilean males. Plasma samples were collected over a 12-hour period after administration of 150 mg pregabalin in each period. A validated ultra-performance liquid chromatography with positive ionization mass spectrometric detection method was used to analyze pregabalin concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products was determined when the ratio for the 90% confidence intervals (CIs) of the difference in the means of the log-transformed area under the curve (AUC)(0-t), AUC(0-∞), and maximum concentration (C(max)) of the two products were within 0.80 and 1.25. The study was carried out on 22 healthy Chilean volunteers. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the test formulation (Pregobin™) of pregabalin were 2.10 (0.56) μg/ml, 10.35 (2.00) μgxh/ml and 13.92 (2.74) μgxh/ml, respectively. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the reference formulation (Lyrica™) of pregabalin were 2.15 (0.52) μg/ml, 10.31 (1.85) μgxh/ml and 13.78 (2.25) μgxh/ml, respectively. The parametric 90% CIs for C(max), AUC(0-t), and AUC(0-∞) were 0.97-1.13, 1.01-1.04, and 0.98-1.02, respectively. These results suggest that both products are bioequivalent and can be used as interchangeable options in the clinical setting.

Study of the mass of the electron neutrino in Japan

Energy Technology Data Exchange (ETDEWEB)

Yasumi, Shinjiro; Maezawa, Hideki [eds.

1996-02-01

This report describes a study of the mass of the electron neutrino using electron capture in {sup 163}Ho in Japan for the period from 1981 to 1994. This monograph has two purposes, one is to supplement the papers on the mass of the electron neutrino already published by us and another is to make a record on some details of our experiments for future. Electron capture in a nucleus takes place in a rather small space inside an atom, where atomic physics, nuclear physics and particle physics work closely together. Therefore, this study needed an intimate collaboration of atomic physicists, nuclear physicists and particle physicists. In addition, it was necessary for this study to use various fine techniques, including metallurgy, production of {sup 163}Ho activity, micro-analysis by wet chemistry, isotope-dilution mass spectrometry, undulator radiation source technology, the soft X-ray monochromator technology, a counting technique for very intense soft X-rays and so on. As a result, our collaboration consisted of many researchers from various fields as follows; M. Ando, H. Arai, M. Fujioka, N. Hashimoto, H. Ikeda, Y. Inagaki, K. Ishii, K. Itoh, G. Izawa, O. Kawakami, S. Kishimoto, H. Kitamura, H. Maezawa, M. Maruyama, A. Masuda, K. Masumoto, A. Mikuni, T. Mizogawa, T. Mukoyama, F. Ochiai, T. Ohta, T. Omori, G. Rajasekaran, K. Sera, K. Shima, T. Shinozuka, P.M. Stefan, I. Sugai, H. Taketani, M. Yagi, and S. Yasumi. Without such an excellent collaboration, this study would not have been completed. We would like to express our sincere gratitude to Professor T. Sasaki for supporting this study and recommending the undulator beam line of 2.5 GeV Photon Factory Storage Ring as a light source to be used in the experiment. We also would like to thank Dr. A. Yagishita and Dr. Y. Kitajima who are responsible for the BL-2 beamline. Finally we are grateful to Ms. M. Noji for her patient typewriting of manuscripts written by hand. (author).

Study of the mass of the electron neutrino in Japan

International Nuclear Information System (INIS)

Yasumi, Shinjiro; Maezawa, Hideki

1996-02-01

This report describes a study of the mass of the electron neutrino using electron capture in 163 Ho in Japan for the period from 1981 to 1994. This monograph has two purposes, one is to supplement the papers on the mass of the electron neutrino already published by us and another is to make a record on some details of our experiments for future. Electron capture in a nucleus takes place in a rather small space inside an atom, where atomic physics, nuclear physics and particle physics work closely together. Therefore, this study needed an intimate collaboration of atomic physicists, nuclear physicists and particle physicists. In addition, it was necessary for this study to use various fine techniques, including metallurgy, production of 163 Ho activity, micro-analysis by wet chemistry, isotope-dilution mass spectrometry, undulator radiation source technology, the soft X-ray monochromator technology, a counting technique for very intense soft X-rays and so on. As a result, our collaboration consisted of many researchers from various fields as follows; M. Ando, H. Arai, M. Fujioka, N. Hashimoto, H. Ikeda, Y. Inagaki, K. Ishii, K. Itoh, G. Izawa, O. Kawakami, S. Kishimoto, H. Kitamura, H. Maezawa, M. Maruyama, A. Masuda, K. Masumoto, A. Mikuni, T. Mizogawa, T. Mukoyama, F. Ochiai, T. Ohta, T. Omori, G. Rajasekaran, K. Sera, K. Shima, T. Shinozuka, P.M. Stefan, I. Sugai, H. Taketani, M. Yagi, and S. Yasumi. Without such an excellent collaboration, this study would not have been completed. We would like to express our sincere gratitude to Professor T. Sasaki for supporting this study and recommending the undulator beam line of 2.5 GeV Photon Factory Storage Ring as a light source to be used in the experiment. We also would like to thank Dr. A. Yagishita and Dr. Y. Kitajima who are responsible for the BL-2 beamline. Finally we are grateful to Ms. M. Noji for her patient typewriting of manuscripts written by hand. (author)

Electronic Document Management: A Human Resource Management Case Study

Directory of Open Access Journals (Sweden)

Thomas Groenewald

2004-11-01

Full Text Available This case study serve as exemplar regarding what can go wrong with the implementation of an electronic document management system. Knowledge agility and knowledge as capital, is outlined against the backdrop of the information society and knowledge economy. The importance of electronic document management and control is sketched thereafter. The literature review is concluded with the impact of human resource management on knowledge agility, which includes references to the learning organisation and complexity theory. The intervention methodology, comprising three phases, follows next. The results of the three phases are presented thereafter. Partial success has been achieved with improving the human efficacy of electronic document management, however the client opted to discontinue the system in use. Opsomming Die gevalle studie dien as voorbeeld van wat kan verkeerd loop met die implementering van ’n elektroniese dokumentbestuur sisteem. Teen die agtergrond van die inligtingsgemeenskap en kennishuishouding word kennissoepelheid en kennis as kapitaal bespreek. Die literatuurstudie word afgesluit met die inpak van menslikehulpbronbestuur op kennissoepelheid, wat ook die verwysings na die leerorganisasie en kompleksietydsteorie insluit. Die metodologie van die intervensie, wat uit drie fases bestaan, volg daarna. Die resultate van die drie fases word vervolgens aangebied. Slegs gedeelte welslae is behaal met die verbetering van die menslike doeltreffendheid ten opsigte van elektroniese dokumentbestuur. Die klient besluit egter om nie voort te gaan om die huidige sisteem te gebruik nie.

Study of the fast electron distribution function in lower hybrid and electron cyclotron current driven plasmas in the WT-3 tokamak

International Nuclear Information System (INIS)

Ogura, K.; Tanaka, H.; Ide, S.

1991-01-01

The distribution function f(p-vector) of fast electrons produced by lower hybrid current drive (LHCD) is investigated in the WT-3 tokamak, using a combination of measurements of the hard X-ray (HXR) angular distribution with respect to the toroidal magnetic field and observations of the HXR radial profile. The data obtained indicate the formation of a plateau-like region in f(p-vector) which corresponds to a region of resonant interaction between the lower hybrid (LH) wave and the electrons. The energy of the fast electrons in the peripheral plasma region is observed to be higher than that in the central plasma region under operational conditions with a high plasma current (I p ≥ 80 kA). At low current (I p < or approx. 50 kA), however, the energy of fast electrons is constant along the plasma radius. In the current ramp-up phase, fast electrons are generated in the directions normal to and opposite to the LH wave propagation. The latter case is ascribed to a negatively biased toroidal electric field induced by the current ramp-up. To study the characteristic change of f(p-vector) for various current drive mechanisms, HXR measurements are performed in electron cyclotron current driven (ECCD) plasma and in Ohmic heating (OH) plasma. In ECCD plasma, the perpendicular energy of fast electrons increases, which indicates that fast electrons are accelerated perpendicularly by electron cyclotron heating. In both LHCD and ECCD plasmas, fast electrons flow in the direction opposite to the wave propagation, while no such fast electrons are formed in OH plasma. (author). 33 refs, 16 figs, 1 tab

Study on Effects of Electron Donors on Phosphine Production from Anaerobic Activated Sludge

Directory of Open Access Journals (Sweden)

Jianping Cao

2017-07-01

Full Text Available The effects of different types and concentrations of electron donors (glucose, starch, methanol and sodium acetate on the formation of phosphine from anaerobic activated sludge that has been domesticated for a prolonged period were studied in small batch experiments. The results show that types and concentrations of electron donor have significant effects on the production of phosphine from anaerobic activated sludge. Among them, glucose was the most favourable electron donor, whereas sodium acetate was the least favourable electron donor for the removal of phosphorus and the production of phosphine. Higher concentrations of electron donors were more favourable for the reduction of phosphate into phosphine, and supplying more than nine times the amount of electron donor as theoretically required for the reduction of phosphate into phosphine was favourable for the production of phosphine.

First-principles study of electron transport through monatomic Al and Na wires

DEFF Research Database (Denmark)

Kobayashi, Nobuhiko; Brandbyge, Mads; Tsukada, Masaru

2000-01-01

We present first-principles calculations of electron transport, in particular, the conduction channels of monatomic Al and Na atom wires bridged between metallic jellium electrodes. The electronic structures are calculated by the first-principles recursion-transfer matrix method, and the conduction...... channels are investigated using the eigenchannel decomposition (ECD) of the conductance, the local density of states (LDOS), and the current density. The ECD is different from the conventional decomposition of atomic orbitals, and the study of decomposed electronic structures is shown to be effective...

[Scanning electron microscope study of chemically disinfected endodontic files].

Science.gov (United States)

Navarro, G; Mateos, M; Navarro, J L; Canalda, C

1991-01-01

Forty stainless steel endodontic files were observed at scanning electron microscopy after being subjected to ten disinfection cycles of 10 minutes each one, immersed in different chemical disinfectants. Corrosion was not observed on the surface of the files in circumstances that this study was made.

Study of loading by beam of dual-resonator structure of linear electron accelerator

International Nuclear Information System (INIS)

Milovanov, O.S.; Smirnov, I.A.

1988-01-01

Loading by the beam of the accelerating structure of an Argus dual-resonator linear electron accelerator with a kinetic energy of ∼ 1 MeV and a pulsed beam current of up to 0.5 A is studied experimentally. It is shown that the conditions for stable single-frequency operation of the magnetron are disrupted and the acceleration process is cut off at certain electron-beam currents. Experimental curves of the maximum beam current and maximum electron efficiency of the Argus linear electron accelerator as functions of rf power are given

Theoretical Studies of the Electronic Structure of the Compounds of the Actinide Elements

International Nuclear Information System (INIS)

Kaltsoyannis, Nikolas; Hay, P.J.; Li, Jun; Blaudeau, Jean-Philippe; Bursten, Bruce E.

2006-01-01

In this chapter, we will present an overview of the theoretical and computational developments that have increased our understanding of the electronic structure of actinide-containing molecules and ions. The application of modern electronic structure methodologies to actinide systems remains one of the great challenges in quantum chemistry; indeed, as will be discussed below, there is no other portion of the periodic table that leads to the confluence of complexity with respect to the calculation of ground- and excited-state energies, bonding descriptions, and molecular properties. But there is also no place in the periodic table in which effective computational modeling of electronic structure can be more useful. The difficulties in creating, isolating, and handling many of the actinide elements provide an opportunity for computational chemistry to be an unusually important partner in developing the chemistry of these elements. The importance of actinide electronic structure begins with the earliest studies of uranium chemistry and predates the discovery of quantum mechanics. The fluorescence of uranyl compounds was observed as early as 1833, a presage of the development of actinometry as a tool for measuring photochemical quantum yields. Interest in nuclear fuels has stimulated tremendous interest in understanding the properties, including electronic properties, of small actinide-containing molecules and ions, especially the oxides and halides of uranium and plutonium. The synthesis of uranocene in 1968 led to the flurry of activity in the organometallic chemistry of the actinides that continues today. Actinide organometallics (or organoactinides) are nearly always molecular systems and are often volatile, which makes them amenable to an arsenal of experimental probes of molecular and electronic structure (Marks and Fischer, 1979). Theoretical and computational studies of the electronic structure of actinide systems have developed in concert with the experimental

Electronic properties of diphenyl-s-tetrazine and some related oligomers. An spectroscopic and theoretical study

Energy Technology Data Exchange (ETDEWEB)

Moral, Monica; Garcia, Gregorio [Departamento de Quimica Fisica y Analitica, Facultad de Ciencias Experimentales, Universidad de Jaen, Campus las Lagunillas, E23071 Jaen (Spain); Penas, Antonio [Departamento de Quimica Inorganica y Organica, Facultad de Ciencias Experimentales, Universidad de Jaen, Campus las Lagunillas, E23071 Jaen (Spain); Garzon, Andres; Granadino-Roldan, Jose M. [Departamento de Quimica Fisica y Analitica, Facultad de Ciencias Experimentales, Universidad de Jaen, Campus las Lagunillas, E23071 Jaen (Spain); Melguizo, Manuel [Departamento de Quimica Inorganica y Organica, Facultad de Ciencias Experimentales, Universidad de Jaen, Campus las Lagunillas, E23071 Jaen (Spain); Fernandez-Gomez, Manuel, E-mail: mfg@ujaen.es [Departamento de Quimica Fisica y Analitica, Facultad de Ciencias Experimentales, Universidad de Jaen, Campus las Lagunillas, E23071 Jaen (Spain)

2012-10-26

Highlights: Black-Right-Pointing-Pointer We study properties of Ph{sub 2}Tz and (PhTz){sub n}Ph as candidates for organic electronics. Black-Right-Pointing-Pointer The synthesis of Ph{sub 2}Tz was performed through a modified Pinner-type reaction. Black-Right-Pointing-Pointer IR/Raman spectra allowed to conclude that Ph{sub 2}Tz is nearly planar in liquid phase. Black-Right-Pointing-Pointer Electronic structure was studied by UV-Vis/TD-DFT methods in different solvents. Black-Right-Pointing-Pointer Bandgap, E{sub LUMO}, electron mobility predict some n-type character for limit polymer. -- Abstract: This work presents a theoretical and spectroscopic study on the electronic and structural properties of the diphenyl-s-tetrazine molecule (Ph{sub 2}Tz) and some oligomeric derivatives. Ph{sub 2}Tz was synthesized through a variation of Pinner-type reaction which uses N-acetylcysteine as catalyst. Insight into the structure and electronic properties of the title compound was obtained through IR, Raman, UV-Vis spectra in different solvents, and theoretical calculations. Theoretical studies have been extended to different n-mers derivatives up to an ideal molecular wire through the oligomeric approximation, predicting this way electronic properties such as LUMO energy levels, electron affinity and reorganization energy in order to assess their possible applications in molecular electronics.

Electronic structure of a striped nickelate studied by the exact exchange for correlated electrons (EECE) approach

KAUST Repository

Schwingenschlö gl, Udo; Schuster, Cosima B.; Fré sard, Raymond

2009-01-01

Motivated by a RIXS study of Wakimoto, et al.(Phys. Rev. Lett., 102 (2009) 157001) we use density functional theory to analyze the magnetic order in the nickelate La5/3Sr1/3NiO4 and the details of its crystal and electronic structure. We compare

Application of positron annihilation induced auger electron spectroscopy to the study of surface chemistry

International Nuclear Information System (INIS)

Weiss, A.H.; Yang, G.; Nangia, A.; Kim, J.H.; Fazleev, N.G.

1996-01-01

Positron annihilation induced Auger Electron Spectroscopy (PAES), makes use a beam of low energy positrons to excite Auger transitions by annihilating core electrons. This novel mechanism provides PAES with a number of unique features which distinguishes it from other methods of surface analysis. In PAES the very large collisionally induced secondary electron background which is present under the low energy Auger peaks using conventional techniques can be eliminated by using a positron beam whose energy is below the range of Auger electron energies. In addition, PAES is more surface selective than conventional Auger Spectroscopy because the PAES signal originates almost exclusively from the topmost atomic layer due to the fact that the positrons annihilating with the core electrons are trapped in an image correlation well just outside the surface. In this paper, recent applications of Positron Annihilation Induced Auger Electron Spectroscopy (PAES) to the study of surface structure and surface chemistry will be discussed including studies of the growth, alloying and inter-diffusion of ultrathin layers of metals, metals on semiconductors, and semiconductors on semiconductors. In addition, the possibilities for future application of PAES to the study of catalysis and surface chemistry will be outlined. (author)

Color formation study of irradiated polymers by electron beam

International Nuclear Information System (INIS)

Nardi, Daniela Teves

2004-01-01

Color formation on national and commercial polymers (polymethyl methacrylate, polystyrene and polycarbonate) irradiated by electrons beam was investigated by colorimetry (CIELab), electron spectroscopy resonance (ESR), photoacoustic infrared spectroscopy (FTIR-PAS) and differential exploratory calorimetry (DSC). The heat effect on colorimetric properties was investigated after heating (110 deg C for 1 hour) of irradiated polymers at 150 kGy. The rule of oxygen in colorimetric properties of irradiated polycarbonate was investigated in the air presence and absence (p = 10 -3 mmHg). The visual aspect did not agree with colorimetric parameters only for polycarbonate. Yellow color and darkness were induced by radiation for all studied polymers varying only the intensity and behavior in function of post-irradiation time and heating. Polymethyl methacrylate and polystyrene ESR spectra showed that radicals could be responsible by yellow color centers. Wherever, in polycarbonate, color centers were not due radical species. The nature of color centers for any studied polymer was not study by FTIR-PAS because there were no changes in FTIR-PAS spectra neither in function of dose nor heating. Polycarbonate was the most radiosensible and polystyrene was the most radioresistant of all studied polymers in concern of colorimetric properties. (author)

Electronic processes in organic electronics bridging nanostructure, electronic states and device properties

CERN Document Server

Kudo, Kazuhiro; Nakayama, Takashi; Ueno, Nobuo