Home About us Contact
|
Home About us Contact | ||
|
|
||
Increased Throughput (increased + throughput)
Selected AbstractsRapid throughput screening of apparent KSP values for weakly basic drugs using 96-well formatJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2008Jeremy Guo Abstract A rapid-throughput screening assay was developed to estimate the salt solubility parameter, KSP, with a minimal quantity of drug. This assay allows for early evaluation of salt limited solubility with a large number of counter-ions and biologically promising drug leads. Drugs dissolved (typically 10 mM) in DMSO are robotically distributed to a 96-well plate. DMSO is evaporated, and drugs are equilibrated with various acids at different concentrations (typically <1 M) to yield final total drug concentrations around 2.5 mM. The plate is checked for precipitation. Filtrates from only those precipitated wells were subjected to rapid gradient HPLC analysis. An iterative procedure is employed to calculate all species concentrations based on mass and charge balance equations. The apparent KSP values assuming 1:1 stoichiometry are determined from counter-ion and ionized drug activities. A correlation coefficient >0.975 for eight drugs totaling 16 salts is reported. Intra-day and inter-day reproducibility was <10%. Conventional apparent KSP measurements were translated to 96-well format for increased throughput and minimal drug consumption (typically 10 mg) to evaluate at least eight different counter-ions. Although the current protocol estimates KSP from 10,3 to 10,7 M, the dynamic range of the assay could be expanded by adjusting drug and counter-ion concentrations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2079,2090, 2008 [source] Thin film solar modules: the low cost, high throughput and versatile alternative to Si wafersPROGRESS IN PHOTOVOLTAICS: RESEARCH & APPLICATIONS, Issue 5 2006S. Hegedus Abstract Thin film solar cells (TFSC) have passed adolescence and are ready to make a substantial contribution to the world's electricity generation. They can have advantages over c-Si solar modules in ease of large area, lower cost manufacturing and in several types of applications. Factors which limit TFSC module performance relative to champion cell performance are discussed along with the importance of increased throughput and yield. The consensus of several studies is that all TFSC can achieve costs below 1,$/W if manufactured at sufficiently large scale >100,MW using parallel lines of cloned equipment with high material utilization and spray-on encapsulants. There is significant new commercial interest in TFSC from small investors and large corporations, validating the thin film approach. Unique characteristics are discussed which give TFSC an advantage over c-Si in two specific markets: small rural solar home systems and building integrated photovoltaic installations. TFSC have outperformed c-Si in annual energy production (kWhrs/kW), have demonstrated outdoor durability comparable to c-Si and are being used in MW scale installations worldwide. The merits of the thin film approach cannot be judged on the basis of efficiency alone but must also account for module performance and potential for low cost. TFSC advocates should promote their unique virtues compared to c-Si: lower cost, higher kWhr/kW output, higher battery charging current, attractive visual appearance, flexible substrates, long-term stability comparable to c-Si, and multiple pathways for deposition with room for innovation and evolutionary improvement. There is a huge market for TFSC even at today's efficiency if costs can be reduced. A brief window of opportunity exists for TFSC over the next few years due the Si shortage. The demonstrated capabilities and advantages of TFSC must be proclaimed more persistently to funding decision-makers and customers without minimizing the remaining challenges. Copyright © 2006 John Wiley & Sons, Ltd. [source] Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discoveryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2001Walter A. Korfmacher This report addresses the continuing need for increased throughput in the evaluation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK) parameters by describing an alternative procedure for increasing the throughput of the in vivo screening of NCEs in the oral rat PK model. The new approach is called ,cassette-accelerated rapid rat screen' (CARRS). In this assay, NCEs are dosed individually (n,=,2 rats/compound) in batches of six compounds per set. The assay makes use of a semi-automated protein precipitation procedure for sample preparation in a 96-well plate format. The liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) assay is also streamlined by analyzing the samples as ,cassettes of six'. Using this new approach, a threefold increase in throughput was achieved over the previously reported ,rapid rat screen'. Copyright © 2001 John Wiley & Sons, Ltd. [source] Validation of a differential in situ perfusion method with mesenteric blood sampling in rats for intestinal drug interaction profilingBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5-6 2010Joachim Brouwers Abstract The present study explored the feasibility of a differential setup for the in situ perfusion technique with mesenteric cannulation in rats to assess drug interactions at the level of intestinal absorption. In contrast to the classic, parallel in situ perfusion setup, the differential approach aims to identify intestinal drug interactions in individual animals by exposing the perfused segment to a sequence of multiple conditions. First, the setup was validated by assessing the interaction between the P-glycoprotein (P-gp) inhibitor verapamil and the transport probes atenolol (paracellular transport), propranolol (transcellular) and talinolol (P-gp mediated efflux). While transport of atenolol and propranolol remained constant for the total perfusion time (2,h), a verapamil-induced increase in talinolol transport was observed within individual rats (between 3.2- and 5.2-fold). In comparison with the parallel setup, the differential in situ perfusion approach enhances the power to detect drug interactions with compounds that exhibit strong subject-dependent permeability. This was demonstrated by identifying an interaction between amprenavir and ketoconazole (P-gp and CYP3A inhibitor) in five out of seven rats (permeability increase between 1.9- and 4.2-fold), despite high inter-individual differences in intrinsic permeability for amprenavir. In combination with an increased throughput (up to 300%) and a reduced animal use (up to 50%), the enhanced power of the differential approach improves the utility of the biorelevant in situ perfusion technique with mesenteric blood sampling to elucidate the intestinal interaction profile of drugs and drug candidates. Copyright © 2010 John Wiley & Sons, Ltd. [source] The benefit of geriatric intervention in surgery,increased throughput does not necessarily need more bedsCOLORECTAL DISEASE, Issue 6 2000R. B. Dunn Objective Three years ago a consultant geriatrician began regular visits to the coloproctology and general surgery wards of an acute Trust every weekday, to assist staff with the medical management, rehabilitation and discharge planning of patients aged 65 years and above. The length of stay of these patients in the first 10 months of the appointment was compared with younger concurrent controls and with historical controls in the preceding 10 months. Results The mean length of stay for the 4146 patients aged 16 years and above in a 10-month intervention period was 1.3 days shorter (95% confidence interval (CI) 0.86,1.74 days) than for the 4002 patients in the 10-month control period. This pattern was consistent across all ages and types of surgery, including major colorectal resection. Conclusion There was an important benefit to the availability of coloproctology and general surgical beds in this acute Trust. More efficient rehabilitation of elderly patients reduces ,bed blockage' post-operatively, and allows more effective use of available resources. Co-ordination of the geriatric service with the specialized stoma support service allows earlier discharge of the elderly, and their relocation to appropriate premises where long-term changes in bowel habit and problems with stoma care can be managed away from the acute surgical unit. [source] | |||||||||||||