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Sample records for absorption window drug

  1. Statistical Design of Experiments on Fabrication of Bilayer Tablet of Narrow Absorption Window Drug: Development and In vitro characterisation.

    PubMed

    Jivani, R R; Patel, C N; Jivani, N P

    2012-07-01

    The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm(2), respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet.

  2. Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification.

    PubMed

    Cvijić, Sandra; Parojčić, Jelena; Langguth, Peter

    2014-09-30

    Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.

  3. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

    PubMed Central

    Pathak, Kamla

    2014-01-01

    Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain. PMID:25478230

  4. Low-Absorption Laser Windows

    DTIC Science & Technology

    1976-04-01

    Halides 20 AB^rWACT (Continue on reverse side II necessary mnd Identity by block number) This semiannual report summarizes work by NRL under ARPA...20375, under ARPA Order 3006. The program was coordinated by Dr, P. H. Klein of NRL, and monitored by Dr. C. M. Stickley and CAPT II. Winsor of ARPA...of lowloss laser- window materials. This work, under ARPA Order 3066, is a direct outgrowth of that begun under ARPA Order 2031. (The two

  5. Water vapor absorption in the atmospheric window at 239 GHz

    NASA Technical Reports Server (NTRS)

    Bauer, A.; Godon, M.; Carlier, J.; Ma, Q.

    1995-01-01

    Absolute absorption rates of pure water vapor and mixtures of water vapor and nitrogen have been measured in the atmospheric window at 239 GHz. The dependence on pressure as well as temperature has been obtained. The experimental data are compared with several theoretical or empirical models, and satisfactory agreement is obtained with the models involving a continuum; in the case of pure water vapor, the continuum contribution based upon recent theoretical developments gives good results. The temperature dependence is stronger than that proposed in a commonly used atmospheric transmission model.

  6. Phosphine absorption in the 5-micron window of Jupiter

    NASA Technical Reports Server (NTRS)

    Beer, R.; Taylor, F. W.

    1979-01-01

    Since the original suggestion by Gillett et al. (1969) it has generally been assumed that the region of partial transparency near 5 micron in Jupiter's atmosphere (the 5-micron window) is bounded by the nu sub 4 NH3 at 6.1 micron and the nu sub 3 CH4 band at 3.3 micron. New measurements of Jupiter and of laboratory phosphine (PH3) samples show that PH3 is a significant contributor to the continuum opacity in the window and in fact defines its short-wavelength limit. This has important implications for the use of 5-micron observations as a means to probe the deep atmospheric structure of Jupiter. The abundance of PH3 which results from a comparison of Jovian and laboratory spectra is about 3 to 5 cm-am. This is five to eight times less than that found by Larson et al. (1977) in the same spectral region, but is in good agreement with the result of Tokunaga et al. (1979) from 10-micron observations.

  7. Water vapour foreign-continuum absorption in near-infrared windows from laboratory measurements.

    PubMed

    Ptashnik, Igor V; McPheat, Robert A; Shine, Keith P; Smith, Kevin M; Williams, R Gary

    2012-06-13

    For a long time, it has been believed that atmospheric absorption of radiation within wavelength regions of relatively high infrared transmittance (so-called 'windows') was dominated by the water vapour self-continuum, that is, spectrally smooth absorption caused by H(2)O--H(2)O pair interaction. Absorption due to the foreign continuum (i.e. caused mostly by H(2)O--N(2) bimolecular absorption in the Earth's atmosphere) was considered to be negligible in the windows. We report new retrievals of the water vapour foreign continuum from high-resolution laboratory measurements at temperatures between 350 and 430 K in four near-infrared windows between 1.1 and 5 μm (9000-2000 cm(-1)). Our results indicate that the foreign continuum in these windows has a very weak temperature dependence and is typically between one and two orders of magnitude stronger than that given in representations of the continuum currently used in many climate and weather prediction models. This indicates that absorption owing to the foreign continuum may be comparable to the self-continuum under atmospheric conditions in the investigated windows. The calculated global-average clear-sky atmospheric absorption of solar radiation is increased by approximately 0.46 W m(-2) (or 0.6% of the total clear-sky absorption) by using these new measurements when compared with calculations applying the widely used MTCKD (Mlawer-Tobin-Clough-Kneizys-Davies) foreign-continuum model.

  8. Intracochlear drug injections through the round window membrane: Measures to improve drug retention

    PubMed Central

    Plontke, Stefan K.; Hartsock, Jared J.; Gill, Ruth M.; Salt, Alec N.

    2016-01-01

    The goal of this study was to develop appropriate methodology to apply drugs quantitatively to perilymph of the ear. Intratympanic applications of drugs to the inner ear often result in variable drug levels in perilymph and can only be used for molecules that readily permeate the round window (RW) membrane. Direct intracochlear and intralabyrinthine application procedures for drugs, genes or cell-based therapies by-pass the tight boundaries at the round window, oval window, otic capsule and the blood-labyrinth barrier. However, perforations can release inner ear pressure, allowing cerebrospinal fluid to enter through the cochlear aqueduct, displacing the injected drug solution into the middle ear. Two markers, fluorescein or fluorescein isothiocyanate (FITC)-labeled dextran, were used to quantify how much of an injected substance was retained in cochlear perilymph following an intracochlear injection. We evaluated whether procedures to mitigate fluid leaks improved marker retention in perilymph. Almost all procedures to reduce volume efflux, including the use of gel for internal sealing and glue for external sealing of the injection site, resulted in improved retention of the marker in perilymph. Adhesive on the RW membrane effectively prevented leaks but also influenced fluid exchange between CSF and perilymph. We conclude that drugs can be delivered to the ear in a consistent, quantitative manner using intracochlear injections if care is taken to control the fluid leaks that result from cochlear perforation. PMID:26905306

  9. In vivo gastrointestinal drug-release monitoring through second near-infrared window fluorescent bioimaging with orally delivered microcarriers

    NASA Astrophysics Data System (ADS)

    Wang, Rui; Zhou, Lei; Wang, Wenxing; Li, Xiaomin; Zhang, Fan

    2017-03-01

    Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance. Here, we report a novel microcarrier that can retain drugs and withstand the harsh conditions of gastrointestinal tract. Significantly, we can track the microcarrier fate and semi-quantitatively monitor the content of drug released in vivo in real time by measuring the fluorescence signals in the second near-infrared window of lanthanide-based downconversion nanoparticles with an absorption competition-induced emission bioimaging system. The microcarriers show a prolonged residence time of up to 72 h in the gastrointestinal tract, releasing up to 62% of their content. Moreover, minimal deposition of the microcarriers is found in non-target organs, such as the liver, spleen and kidney. These findings provide novel insights for the development of therapeutic and bioimaging strategies of orally administered drugs.

  10. Systematic investigation of time windows for adverse event data mining for recently approved drugs.

    PubMed

    Hochberg, Alan M; Hauben, Manfred; Pearson, Ronald K; O'Hara, Donald J; Reisinger, Stephanie J

    2009-06-01

    The optimum timing of drug safety data mining for a new drug is uncertain. The objective of this study was to compare cumulative data mining versus mining with sliding time windows. Adverse Event Reporting System data (2001-2005) were studied for 27 drugs. A literature database was used to evaluate signals of disproportionate reporting (SDRs) from an urn model data-mining algorithm. Data mining was applied cumulatively and with sliding time windows from 1 to 4 years in width. Time from SDR generation to the appearance of a publication describing the corresponding adverse event was calculated. Cumulative data mining and 1- to 2-year sliding windows produced the most SDRs for recently approved drugs. In the first postmarketing year, data mining produced SDRs an average of 800 days in advance of publications regarding the corresponding drug-event combination. However, this timing advantage reduced to zero by year 4. The optimum window width for sliding windows should increase with time on the market. Data mining may be most useful for early signal detection during the first 3 years of a drug's postmarketing life. Beyond that, it may be most useful for supporting or weakening hypotheses.

  11. Genetically modified mouse models for oral drug absorption and disposition.

    PubMed

    Tang, Seng Chuan; Hendrikx, Jeroen J M A; Beijnen, Jos H; Schinkel, Alfred H

    2013-12-01

    Intestinal absorption is an essential step in the therapeutic use of most orally administered drugs and often mediated by enterocyte transmembrane transporters. Here we discuss several of these drug transport systems and knockout mouse models to study them. These studies showed that Multidrug resistance-associated protein 2 (Mrp2) can limit intestinal drug absorption. Organic cation transporter n1 (Octn1) and Octn2 might also facilitate intestinal drug absorption, although direct in vivo evidence is lacking. On the other hand, intestinal uptake of drugs is facilitated by the Equilibrative nucleoside transporter 1 (Ent1), Mrp3 and possibly Mrp4. No significant role in intestinal absorption for Oct1 and Oct2 or for Organic anion-transporting polypeptides (Oatp) 1a and 1b was found so far.

  12. The water vapour self- and water-nitrogen continuum absorption in the 1000 and 2500 cm(-1) atmospheric windows.

    PubMed

    Baranov, Yu I; Lafferty, W J

    2012-06-13

    The pure water vapour and water-nitrogen continuum absorption in the 1000 and 2500 cm(-1) atmospheric windows has been studied using a 2 m base-length White-type multi-pass cell coupled with a BOMEM DA3-002 Fourier transform infrared spectrometer. The measurements were carried out at the National Institute of Standards and Technology (NIST, Gaithersburg, MD) over the course of several years (2004, 2006-2007, 2009). New data on the H(2)O:N(2) continuum in the 1000 cm(-1) window are presented and summarized along with the other experimental results and the continuum model. The experimental data reported on the water vapour continuum in these atmospheric windows basically agree with the most reliable laboratory data from the other sources. The MT_CKD (Mlawer-Tobin-Clough-Kneizys-Davies) continuum model significantly departs from the experimental data in both windows. The deviation observed includes the continuum magnitude, spectral behaviour and temperature dependence. In the 2500 cm(-1) region, the model does not allow for the nitrogen fundamental collision-induced absorption (CIA) band intensity enhancement caused by H(2)O:N(2) collisions and underestimates the actual absorption by over two orders of magnitude. The water vapour continuum interpretation as a typical CIA spectrum is reviewed and discussed.

  13. An interesting relationship between drug absorption and melting point.

    PubMed

    Chu, Katherine A; Yalkowsky, Samuel H

    2009-05-21

    The ability to predict the extent of passive intestinal drug absorption is very important for efficient lead candidate selection and development. Physicochemical-based absorption predictive models previously developed use solubility, partition coefficient and pK(a) as drug input parameters for intestinal absorption. Alternatively, this study looks at the relationship between melting point and passive transport for poorly soluble drugs. It is based entirely on the expression derived from the General Solubility Equation (GSE) that relates melting point to the product of intrinsic solubility and partition coefficient. Given that the melting point of a compound is one of the first and more reliable physical properties measured, it can be advantageously used as a guide in early drug discovery and development. This paper elucidates the interesting relationship between the melting point and dose to the fraction absorbed of poorly soluble drugs, i.e., class II and IV compounds in the Biopharmaceutics Classification System. The newly defined melting point based absorption potential (MPbAP) parameter is successful at distinguishing 90% of the 91 drugs considered being well absorbed (FA>0.5) or poorly absorbed. In general, lower melting compounds are more likely to be well absorbed than higher melting compounds for any given dose. The fraction absorbed for drugs with high melting temperatures is limited by the dose to a greater degree than it is for low melting compounds.

  14. Intracochlear Drug Delivery through the Oval Window in Fresh Cadaveric Human Temporal Bones

    PubMed Central

    Kang, Woo Seok; Nguyen, Kim; McKenna, Charles E.; Sewell, William F.; McKenna, Michael J.; Jung, David H.

    2015-01-01

    Hypothesis Drug delivered to the oval window can diffuse to the apex of the human cochlea. Background We have previously demonstrated that zoledronate, a nitrogen-containing bisphosphonate, can arrest the sensorineural hearing loss in cochlear otosclerosis. We have also shown that, in animals, delivery of bisphosphonate into the cochlea can dramatically increase delivery efficiency. Intracochlear drug delivery has the potential to increase local concentration of drug while decreasing the risk of systemic toxicity. In the present study, a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) was introduced into the human cochlea through the oval window and its distribution within the temporal bone was quantified. Methods In three fresh human temporal bones, we introduced 6-FAM-ZOL via the oval window. We compared these specimens to control specimens treated with artificial perilymph alone. Specimens were then processed, embedded into methyl methacrylate, and ground to the mid-modiolar axis. We quantified the fluorescence in confocal images. Results We found 6-FAM-ZOL to be distributed up to the apical cochlear turn. In specimens treated with 6-FAM-ZOL, we identified a strong baso-apical gradient of fluorescent signal along the lateral cochlear wall and the modiolus both in the scala vestibuli and in the scala tympani. Conclusions Bisphosphonate introduced via the oval window in the human cochlea can be delivered up to the apical cochlear turn. Inter-scalar communication is likely to play an important role in determining patterns of drug delivery in the inner ear. PMID:26859540

  15. Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum.

    PubMed

    Kishimoto, Hisanao; Miyazaki, Kaori; Takizawa, Yusuke; Shirasaka, Yoshiyuki; Inoue, Katsuhisa

    2016-02-01

    Nitric oxide (NO), an endogenous gas that plays a versatile role in the physiological system, has the ability to increase the intestinal absorption of water-soluble compounds through the paracellular route. However, it remains unclear whether NO can enhance the absorption of hydrophobic drugs through the transcellular route. In this study, we examined the absorption-enhancing effect of NO on intestinal permeability of hydrophobic drugs in rat intestine. The pretreatment of rat gastrointestinal sacs with NOC7, a NO-releasing reagent, significantly increased the permeation of griseofulvin from mucosa to serosa in the sacs prepared from the duodenum, but not in those prepared from the other regions such as jejunum, ileum, and colon. The absorption-enhancing effect of NOC7 on the duodenal permeation varied depending on the hydrophobicity of the drugs used. Furthermore, NOC7 treatment was found to be apparently ineffective on the griseofulvin permeation in the duodenum pretreated with dithiothreitol (DTT) that was used as a mucus remover, even though the permeation was increased by pretreatment with DTT alone. These results suggest that NO increases the absorption of hydrophobic drugs through the transcellular route in the duodenum by modulating the mucus layer function.

  16. In vivo gastrointestinal drug-release monitoring through second near-infrared window fluorescent bioimaging with orally delivered microcarriers

    PubMed Central

    Wang, Rui; Zhou, Lei; Wang, Wenxing; Li, Xiaomin; Zhang, Fan

    2017-01-01

    Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance. Here, we report a novel microcarrier that can retain drugs and withstand the harsh conditions of gastrointestinal tract. Significantly, we can track the microcarrier fate and semi-quantitatively monitor the content of drug released in vivo in real time by measuring the fluorescence signals in the second near-infrared window of lanthanide-based downconversion nanoparticles with an absorption competition-induced emission bioimaging system. The microcarriers show a prolonged residence time of up to 72 h in the gastrointestinal tract, releasing up to 62% of their content. Moreover, minimal deposition of the microcarriers is found in non-target organs, such as the liver, spleen and kidney. These findings provide novel insights for the development of therapeutic and bioimaging strategies of orally administered drugs. PMID:28281530

  17. Influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions.

    PubMed

    Shen, Cheng-Ying; Li, Rui-Sheng; Shen, Bao-de; Shen, Gang; Wang, Li-Qiang; Zheng, Juan; Li, Xiao-Rong; Min, Hong-Yan; Han, Jin; Yuan, Hai-Long

    2015-01-01

    The purpose of this paper was to study the influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions. Four drug nanosuspensions were produced by high-pressure homogenization technique, which were the same in stabilizer and similar in particle size. Differential scanning calorimetry and powder X-ray diffraction analysis showed that the crystalline state of the nanocrystals did not change. In vitro permeation study demonstrated that the drug nanosuspensions have a higher rate of permeation that ranged from 1.69- to 3.74-fold compared to drug microsuspensions. Correlation analysis between drug physicochemical properties and Jss revealed that log P and pKa were factors that influenced the in vitro transdermal absorption of hydrophobic drug nanosuspensions, and drugs with a log P value around 3 and a higher pKa value (when pKa < pH+2) would gain higher Jss in this paper.

  18. Fundamental understanding of drug absorption from a parenteral oil depot.

    PubMed

    Kalicharan, Raween W; Schot, Peter; Vromans, Herman

    2016-02-15

    Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter.

  19. Drug-induced mitochondrial neuropathy in children: a conceptual framework for critical windows of development.

    PubMed

    Wallace, Kendall B

    2014-09-01

    Mitochondrial disease arises from genetic or nongenetic events that interfere either directly or indirectly with the bioenergetic function of the mitochondrion and manifest clinically in some form of metabolic disorder. In primary mitochondrial disease, the critical molecular target is one or more of the individual subunits of the respiratory complexes or their assembly and incorporation into the inner mitochondrial membrane, whereas with secondary mitochondrial disease the bioenergetic deficits are secondary to effects on targets other than the electron transport chain and oxidative phosphorylation. Primary genetic events include mutations to or altered expression of proteins targeted to the mitochondrial compartment, whether they are encoded by the nuclear or mitochondrial genome. In this review, we emphasize the occurrence of nongenetic mitochondrial disease resulting from therapeutic drug administration, review the broad scope of drugs implicated in affecting specific primary mitochondrial targets, and describe evidence demonstrating critical windows of risk for the developing neonate to drug-induced mitochondrial disease and neuropathy.

  20. Time-resolved x-ray absorption spectroscopy with a water window high-harmonic source

    NASA Astrophysics Data System (ADS)

    Pertot, Yoann; Schmidt, Cédric; Matthews, Mary; Chauvet, Adrien; Huppert, Martin; Svoboda, Vit; von Conta, Aaron; Tehlar, Andres; Baykusheva, Denitsa; Wolf, Jean-Pierre; Wörner, Hans Jakob

    2017-01-01

    Time-resolved x-ray absorption spectroscopy (TR-XAS) has so far practically been limited to large-scale facilities, to subpicosecond temporal resolution, and to the condensed phase. We report the realization of TR-XAS with a temporal resolution in the low femtosecond range by developing a tabletop high-harmonic source reaching up to 350 electron volts, thus partially covering the spectral region of 280 to 530 electron volts, where water is transmissive. We used this source to follow previously unexamined light-induced chemical reactions in the lowest electronic states of isolated CF4+ and SF6+ molecules in the gas phase. By probing element-specific core-to-valence transitions at the carbon K-edge or the sulfur L-edges, we characterized their reaction paths and observed the effect of symmetry breaking through the splitting of absorption bands and Rydberg-valence mixing induced by the geometry changes.

  1. Permeability of the Round Window Membrane is Influenced by the Composition of Applied Drug Solutions and by Common Surgical Procedures

    PubMed Central

    Mikulec, Anthony A.; Hartsock, Jared J.; Salt, Alec N.

    2008-01-01

    Introduction Intratympanic drug delivery has become widely used in the clinic but little is known about how clinically-utilized drug preparations affect round window membrane permeability or how much drug is actually delivered to the cochlea. This study evaluated the effect of clinically relevant carrier solutions and of suction near the round window membrane (RWM) on the permeability properties of the RWM. Methods RWM permeability was assessed by perfusion of the marker TMPA into the round window niche while monitoring entry into perilymph using TMPA-selective electrodes sealed into scala tympani. Results High osmolarity solution increased RWM permeability by a factor of 2 to 3, benzyl alcohol (a preservative used in some drug formulations) increased permeability by a factor of 3 to 5, and suctioning near the RWM increased permeability by a factor of 10 to 15. Conclusions Variations in available drug formulations can potentially alter RWM permeability properties and affect the amount of drug delivered to the inner ear. Drug solution osmolarity, benzyl alcohol content and possible drying of the round window membrane during suctioning the middle ear can all have a substantial influence of the perilymph levels of drug achieved. PMID:18758387

  2. Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

    PubMed

    Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2011-01-05

    Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

  3. Modular Simulation of Absorption Systems User's Guide (Windows Version 5.0)

    SciTech Connect

    Grossman, G

    2000-09-25

    ABSIM (an acronym for ABsorption SIMulation) is a user-oriented computer code designed for the simulation of absorption systems at steady state, in both flexible and modular form. ABSIM makes it possible to investigate various cycle configurations with different working fluids, to calculate their operating parameters, to predict their performance and to compare them with each other on a uniform basis. A graphical user interface enables the user to draw the cycle diagram on the computer screen, enter data interactively, run the program and view the results either in the form of a table or superimposed on the cycle diagram. Special utilities enable the user to plot the results and produce a pressure-temperature-concentration (P-T-X) diagram of the cycle. Most absorption systems consist of a number of standard components or units (e.g., absorber, condenser) that may be combined in different forms to produce various cycles. Recognizing this, ABSIM has been structured around unit subroutines, each of which contains the governing equations for the particular unit. These subroutines are activated by a main program that interprets the input for the cycle, calls the units, and links them to each other in an order corresponding to the user's specification to form the complete system. Each unit subroutine, when activated, addresses a property database for the thermodynamic properties of the working fluids. The equations generated by the code are listed and solved simultaneously by a mathematical solver routine. The code requires relatively simple inputs, consisting of the minimum information needed to define an absorption system properly. After drawing the cycle in terms of the units recognizable by the code and showing their interconnections, the user must specify the size of each exchange unit in terms of its heat and mass transfer characteristics, the working fluid(s) at each state point; and the given operating conditions, such as temperatures, flowrates, and the like

  4. A window into the intoxicated mind? Speech as an index of psychoactive drug effects.

    PubMed

    Bedi, Gillinder; Cecchi, Guillermo A; Slezak, Diego F; Carrillo, Facundo; Sigman, Mariano; de Wit, Harriet

    2014-09-01

    Abused drugs can profoundly alter mental states in ways that may motivate drug use. These effects are usually assessed with self-report, an approach that is vulnerable to biases. Analyzing speech during intoxication may present a more direct, objective measure, offering a unique 'window' into the mind. Here, we employed computational analyses of speech semantic and topological structure after ±3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') and methamphetamine in 13 ecstasy users. In 4 sessions, participants completed a 10-min speech task after MDMA (0.75 and 1.5 mg/kg), methamphetamine (20 mg), or placebo. Latent Semantic Analyses identified the semantic proximity between speech content and concepts relevant to drug effects. Graph-based analyses identified topological speech characteristics. Group-level drug effects on semantic distances and topology were assessed. Machine-learning analyses (with leave-one-out cross-validation) assessed whether speech characteristics could predict drug condition in the individual subject. Speech after MDMA (1.5 mg/kg) had greater semantic proximity than placebo to the concepts friend, support, intimacy, and rapport. Speech on MDMA (0.75 mg/kg) had greater proximity to empathy than placebo. Conversely, speech on methamphetamine was further from compassion than placebo. Classifiers discriminated between MDMA (1.5 mg/kg) and placebo with 88% accuracy, and MDMA (1.5 mg/kg) and methamphetamine with 84% accuracy. For the two MDMA doses, the classifier performed at chance. These data suggest that automated semantic speech analyses can capture subtle alterations in mental state, accurately discriminating between drugs. The findings also illustrate the potential for automated speech-based approaches to characterize clinically relevant alterations to mental state, including those occurring in psychiatric illness.

  5. On the Use of Difference Bands for Modeling SF_6 Absorption in the 10μm Atmospheric Window

    NASA Astrophysics Data System (ADS)

    Faye, Mbaye; Manceron, Laurent; Roy, P.; Boudon, Vincent; Loete, Michel

    2016-06-01

    To model correctly the SF_6 atmospheric absorption requires the knowledge of the spectroscopic parameters of all states involved in the numerous hot bands in the 10,5μm atmospheric transparency window. However, due to their overlapping, a direct analysis of the hot bands near the 10,5μm absorption of SF_6 in the atmospheric window is not possible. It is necessary to use another strategy, gathering information in the far and mid infrared regions on initial and final states to compute the relevant total absorption. In this talk, we present new results from the analysis of spectra recorded at the AILES beamline at the SOLEIL Synchrotron facility. For these measurements, we used a IFS125HR interferometer combined with the synchrotron radiation in the 100-3200 wn range, coupled to a cryogenic multiple pass cell. The optical path length was varied from 45 to 141m with measuring temperatures between 223 and 153+/-5 K. The new information obtained on νb{2}+νb{4}-νb{5}, 2νb{5}-νb{6} and νb{3}+νb{6}-νb{4} allowed to derive improved parameters for νb{5}, 2νb{5} and νb{3}+νb{6}. In turn, they are used to model the more important νb{3}+νb{5}-νb{5} and νb{3}+νb{6}-νb{6} hot band contributions. By including these new parameters in the XTDS model, we substantially improved the SF_6 parameters used to model the atmosphere. F. Kwabia Tchana, F. Willaert, X. Landsheere, J. M. Flaud, L. Lago, M. Chapuis, P. Roy, L. Manceron. A new, low temperature long-pass cell for mid-IR to THz Spectroscopy and Synchrotron Radiation Use. Rev. Sci. Inst. 84, 093101, (2013) C. Wenger, V. Boudon, M. Rotger, M. Sanzharov, and J.-P. Champion,"XTDS and SPVIEW: Graphical tools for Analysis and Simulation of High Resolution Molecular Spectra", J. Mol. Spectrosc. 251, 102 (2008)

  6. Measurement of absorption spectrum of deuterium oxide (D{sub 2}O) and its application to signal enhancement in multiphoton microscopy at the 1700-nm window

    SciTech Connect

    Wang, Yuxin; Wen, Wenhui; Wang, Kai; Wang, Ke; Zhai, Peng; Qiu, Ping

    2016-01-11

    1700-nm window has been demonstrated to be a promising excitation window for deep-tissue multiphoton microscopy (MPM). Long working-distance water immersion objective lenses are typically used for deep-tissue imaging. However, absorption due to immersion water at 1700 nm is still high and leads to dramatic decrease in signals. In this paper, we demonstrate measurement of absorption spectrum of deuterium oxide (D{sub 2}O) from 1200 nm to 2600 nm, covering the three low water-absorption windows potentially applicable for deep-tissue imaging (1300 nm, 1700 nm, and 2200 nm). We apply this measured result to signal enhancement in MPM at the 1700-nm window. Compared with water immersion, D{sub 2}O immersion enhances signal levels in second-harmonic generation imaging, 3-photon fluorescence imaging, and third-harmonic generation imaging by 8.1, 24.8, and 24.7 times with 1662-nm excitation, in good agreement with theoretical calculation based on our absorption measurement. This suggests D{sub 2}O a promising immersion medium for deep-tissue imaging.

  7. Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation.

    PubMed

    Yeap, Yan Yan; Trevaskis, Natalie L; Quach, Tim; Tso, Patrick; Charman, William N; Porter, Christopher J H

    2013-05-06

    The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by coadministration with lipids in food or lipid-based oral formulations. Coadministration with lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phases remain poorly understood. Classically, drug absorption is believed to be a product of the drug concentration in free solution and the apparent permeability across the absorptive membrane. Solubilization in colloidal phases such as mixed micelles increases dissolution rate and total solubilized drug concentrations, but does not directly enhance (and may reduce) the free drug concentration. In the absence of changes to cellular permeability (which is often high for lipophilic, PWSD), significant changes to membrane flux are therefore unexpected. Realizing that increases in effective dissolution rate may be a significant driver of increases in drug absorption for PWSD, we explore here two alternate mechanisms by which membrane flux might also be enhanced: (1) collisional drug absorption where drug is directly transferred from lipid colloidal phases to the absorptive membrane, and (2) supersaturation-enhanced drug absorption where bile mediated dilution of lipid colloidal phases leads to a transient increase in supersaturation, thermodynamic activity and absorption. In the current study, collisional uptake mechanisms did not play a significant role in the absorption of a model PWSD, cinnarizine, from lipid colloidal phases. In contrast, bile-mediated dilution of model intestinal mixed micelles and vesicles led to drug supersaturation. For colloids that were principally micellar, supersaturation was maintained for a period sufficient to promote absorption. In contrast, for primarily vesicular systems, supersaturation resulted in rapid drug precipitation and no increase in drug absorption. This work suggests that ongoing

  8. A time-resolved single-pass technique for measuring optical absorption coefficients of window materials under 100 GPa shock pressures.

    PubMed

    Li, Jun; Zhou, Xianming; Li, Jiabo

    2008-12-01

    An experimental method was developed to perform time-resolved, single-pass optical absorption measurements and to determine absorption coefficients of window materials under strong shock compression up to approximately 200 GPa. Experimental details are described of (i) a configuration to generate an in situ dynamic, bright, optical source and (ii) a sample assembly with a lithium fluoride plate to essentially eliminate heat transfer from the hot radiator into the specimen and to maintain a constant optical source within the duration of the experiment. Examples of measurements of optical absorption coefficients of several initially transparent single crystal materials at high shock pressures are presented.

  9. Food, gastrointestinal pH, and models of oral drug absorption.

    PubMed

    Abuhelwa, Ahmad Y; Williams, Desmond B; Upton, Richard N; Foster, David J R

    2017-03-01

    This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated "mechanism-based" models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability.

  10. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    PubMed

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium.

  11. Targeting Receptors, Transporters and Site of Absorption to Improve Oral Drug Delivery

    PubMed Central

    Hamman, J.H.; Demana, P.H.; Olivier, E.I.

    2007-01-01

    Although the oral route of drug administration is the most acceptable way of self-medication with a high degree of patient compliance, the intestinal absorption of many drugs is severely hampered by different biological barriers. These barriers comprise of biochemical and physical components. The biochemical barrier includes enzymatic degradation in the gastrointestinal lumen, brush border and in the cytoplasm of the epithelial cells as well as efflux transporters that pump drug molecules from inside the epithelial cell back to the gastrointestinal lumen. The physical barrier consists of the epithelial cell membranes, tight junctions and mucus layer. Different strategies have been applied to improve the absorption of drugs after oral administration, which range from chemical modification of drug molecules and formulation technologies to the targeting of receptors, transporters and specialized cells such as the gut-associated lymphoid tissues. This review focuses specifically on the targeting of receptor-mediated endocytosis, transporters and the absorption-site as methods of optimizing intestinal drug absorption. Intestinal epithelial cells express several nutrient transporters that can be targeted by modifying the drug molecule in such a way that it is recognized as a substrate. Receptor-mediated endocytosis is a transport mechanism that can be targeted for instance by linking a receptor substrate to the drug molecule of interest. Many formulation strategies exist for enhancing drug absorption of which one is to deliver drugs at a specific site in the gastrointestinal tract where optimum drug absorption takes place. PMID:21901064

  12. The CO2 absorption spectrum in the 2.3 μm transparency window by high sensitivity CRDS: (I) Rovibrational lines

    NASA Astrophysics Data System (ADS)

    Vasilchenko, S.; Konefal, M.; Mondelain, D.; Kassi, S.; Čermák, P.; Tashkun, S. A.; Perevalov, V. I.; Campargue, A.

    2016-11-01

    The absorption of carbon dioxide is very weak near 2.3 μm which makes this transparency window of particular interest for the study of Venus' lower atmosphere. As a consequence of the weakness of the transitions located in this region, previous experimental data are very scarce and spectroscopic databases provide calculated line lists which should be tested and validated by experiment. In this work, we use the Cavity Ring Down Spectroscopy (CRDS) technique for a high sensitivity characterization of the CO2 absorption spectrum in two spectral intervals of the 2.3 μm window: 4248-4257 and 4295-4380 cm-1 which were accessed using a Distributed Feed Back (DFB) diode laser and a Vertical External Cavity Surface Emitting Laser (VECSEL) as light sources, respectively. The achieved sensitivity (noise equivalent absorption, αmin, on the order of 5×10-10 cm-1) allowed detecting numerous new transitions with intensity values down to 5×10-30 cm/molecule. The rovibrational assignments were performed by comparison with available theoretical line lists in particular those obtained at IAO Tomsk using the global effective operator approach. Hot bands of the main isotopologue and 16O12C18O bands were found to be missing in the HITRAN database while they contribute importantly to the absorption in the region. Additional CRDS spectra of a CO2 sample highly enriched in 18O were recorded in order to improve the spectroscopy of this isotopologue. As a result about 700 lines of 16O12C18O, 16O12C17O, 17O12C18O, 12C18O2 and 13C18O2 were newly measured. The status of the different databases (HITRAN, CDSD, variational calculations) in the important 2.3 μm transparency window is discussed. Possible improvements to correct evidenced deficiencies are suggested.

  13. In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: application of the mechanistic absorption model GI-Sim.

    PubMed

    Sjögren, Erik; Westergren, Jan; Grant, Iain; Hanisch, Gunilla; Lindfors, Lennart; Lennernäs, Hans; Abrahamsson, Bertil; Tannergren, Christer

    2013-07-16

    Oral drug delivery is the predominant administration route for a major part of the pharmaceutical products used worldwide. Further understanding and improvement of gastrointestinal drug absorption predictions is currently a highly prioritized area of research within the pharmaceutical industry. The fraction absorbed (fabs) of an oral dose after administration of a solid dosage form is a key parameter in the estimation of the in vivo performance of an orally administrated drug formulation. This study discloses an evaluation of the predictive performance of the mechanistic physiologically based absorption model GI-Sim. GI-Sim deploys a compartmental gastrointestinal absorption and transit model as well as algorithms describing permeability, dissolution rate, salt effects, partitioning into micelles, particle and micelle drifting in the aqueous boundary layer, particle growth and amorphous or crystalline precipitation. Twelve APIs with reported or expected absorption limitations in humans, due to permeability, dissolution and/or solubility, were investigated. Predictions of the intestinal absorption for different doses and formulations were performed based on physicochemical and biopharmaceutical properties, such as solubility in buffer and simulated intestinal fluid, molecular weight, pK(a), diffusivity and molecule density, measured or estimated human effective permeability and particle size distribution. The performance of GI-Sim was evaluated by comparing predicted plasma concentration-time profiles along with oral pharmacokinetic parameters originating from clinical studies in healthy individuals. The capability of GI-Sim to correctly predict impact of dose and particle size as well as the in vivo performance of nanoformulations was also investigated. The overall predictive performance of GI-Sim was good as >95% of the predicted pharmacokinetic parameters (C(max) and AUC) were within a 2-fold deviation from the clinical observations and the predicted plasma AUC

  14. Small molecule absorption by PDMS in the context of drug response bioassays.

    PubMed

    van Meer, B J; de Vries, H; Firth, K S A; van Weerd, J; Tertoolen, L G J; Karperien, H B J; Jonkheijm, P; Denning, C; IJzerman, A P; Mummery, C L

    2017-01-08

    The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like "Organs-on-Chip", designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS.

  15. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs

    PubMed Central

    Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

    2016-01-01

    With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs. PMID:27455239

  16. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs.

    PubMed

    Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

    2016-07-21

    With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs.

  17. Accurate measurements and temperature dependence of the water vapor self-continuum absorption in the 2.1 μm atmospheric window.

    PubMed

    Ventrillard, I; Romanini, D; Mondelain, D; Campargue, A

    2015-10-07

    In spite of its importance for the evaluation of the Earth radiative budget, thus for climate change, very few measurements of the water vapor continuum are available in the near infrared atmospheric windows especially at temperature conditions relevant for our atmosphere. In addition, as a result of the difficulty to measure weak broadband absorption signals, the few available measurements show large disagreements. We report here accurate measurements of the water vapor self-continuum absorption in the 2.1 μm window by Optical Feedback Cavity Enhanced Absorption Spectroscopy (OF-CEAS) for two spectral points located at the low energy edge and at the center of the 2.1 μm transparency window, at 4302 and 4723 cm(-1), respectively. Self-continuum cross sections, CS, were retrieved with a few % relative uncertainty, from the quadratic dependence of the spectrum base line level measured as a function of water vapor pressure, between 0 and 16 Torr. At 296 K, the CS value at 4302 cm(-1) is found 40% higher than predicted by the MT_CKD V2.5 model, while at 4723 cm(-1), our value is 5 times larger than the MT_CKD value. On the other hand, these OF-CEAS CS values are significantly smaller than recent measurements by Fourier transform spectroscopy at room temperature. The temperature dependence of the self-continuum cross sections was also investigated for temperatures between 296 K and 323 K (23-50 °C). The derived temperature variation is found to be similar to that derived from previous Fourier transform spectrometer (FTS) measurements performed at higher temperatures, between 350 K and 472 K. The whole set of measurements spanning the 296-472 K temperature range follows a simple exponential law in 1/T with a slope close to the dissociation energy of the water dimer, D0 ≈ 1100 cm(-1).

  18. High resolution absorption cross sections in the transmission window region of the Schumann-Runge bands and Herzberg continuum of O2

    NASA Technical Reports Server (NTRS)

    Yoshino, K.; Esmond, J. R.; Cheung, A. S.-C.; Freeman, D. E.; Parkinson, W. H.

    1992-01-01

    Results are presented on measurements, conducted in the wavelength region 180-195 nm, and at different pressures of oxygen (between 2.5-760 torr) in order to separate the pressure-dependent absorption from the main cross sections, of the absorption cross sections of the Schumann-Runge bands in the window region between the rotational lines of S-R bands of O2. The present cross sections supersede the earlier published cross sections (Yoshino et al., 1983). The combined cross sections are presented graphically; they are available at wavenumber intervals of about 0.1/cm from the National Space Science Data Center. The Herzberg continuum cross sections are derived after subtracting calculated contributions from the Schumann-Runge bands. These are significantly smaller than any previous measurements.

  19. Extraction of full absorption peaks in airborne gamma-spectrometry by filtering techniques coupled with a study of the derivatives. Comparison with the window method.

    PubMed

    Guillot, L

    2001-01-01

    In this paper, an adaptation of a spectral profile analysis method, currently used in high-resolution spectrometry, to airborne gamma measurements is presented. A new algorithm has been developed for extraction of full absorption peaks by studying the variations in the spectral profile of data recorded with large-volume NaI detectors (16 l) with a short sampling time (2 s). The use of digital filters, taking into consideration the characteristics of the absorption peaks, significantly reduced the counting fluctuations, making detection possible based on study of the first and second derivatives. The absorption peaks are then obtained by modelling, followed by subtraction of the Compton continuum in the detection window. Compared to the conventional stripping ratio method, spectral profile analysis offers similar performance for the natural radioelements. The 137Cs 1SD detection limit is approximately 1200 Bq/m2 in a natural background of 200 Bq/kg 40K, 33 Bq/kg 238U and 33 Bq/kg 232Th. At low energy the very high continuum leads to detection limits similar to those obtained by the windows method, but the results obtained are more reliable. In the presence of peak overlaps, however, analysis of the spectral profile alone is not sufficient to separate the peaks, and further processing is necessary. Within the framework of environmental monitoring studies, spectral profile analysis is of great interest because it does not require any assumptions about the nature of the nuclides. The calculation of the concentrations from the results obtained is simple and reliable, since only the full absorption contributions are taken into consideration. A quantitative estimate of radioactive anomalies can thus be obtained rapidly.

  20. Transient Supersaturation Supports Drug Absorption from Lipid-Based Formulations for Short Periods of Time, but Ongoing Solubilization Is Required for Longer Absorption Periods.

    PubMed

    Crum, Matthew F; Trevaskis, Natalie L; Pouton, Colin W; Porter, Christopher J H

    2017-02-06

    The current studies sought to explore the impact of drug supersaturation and precipitation during the dispersion and digestion of lipid-based formulations (LBFs), on in vivo absorption using a coupled in vitro digestion-in vivo perfusion absorption model. Fenofibrate absorption was evaluated from a number of LBFs with different solubilization and supersaturation capacities, and conditions at the absorptive membrane manipulated by changing perfusion conditions, intestine segment lengths, and by the conduct of experiments in the presence or absence of suspended/precipitated drug. LBF dispersion and digestion resulted in varying periods of supersaturation across the different formulations. Even fleeting (5-10 min) periods of supersaturation were able to drive flux across a perfused 10 cm intestinal segment for up to 60 min, although over longer infusion periods (60-80 min) flux dropped in the absence of ongoing drug solubilization and supersaturation. In contrast, the presence or absence of precipitated/suspended drug, had little impact on drug flux. When perfused intestinal segment lengths were extended, the role of initial supersaturation was attenuated and ongoing solubilization conditions became the primary driver of absorptive flux. The data suggest that for highly permeable drugs such as fenofibrate, a short period of supersaturation at the absorptive membrane may be sufficient to drive absorptive drug flux in spite of significant drug precipitation on formulation dispersion or digestion in vitro. In contrast, where longer periods of absorption are required, for example, at higher doses, the requirement for ongoing solubilization and supersaturation becomes more apparent.

  1. Drug-drug interactions related to altered absorption and plasma protein binding: theoretical and regulatory considerations, and an industry perspective.

    PubMed

    Hochman, Jerome; Tang, Cuyue; Prueksaritanont, Thomayant

    2015-03-01

    Drug-drug interactions (DDIs) related to altered drug absorption and plasma protein binding have received much less attention from regulatory agencies relative to DDIs mediated via drug metabolizing enzymes and transporters. In this review, a number of theoretical bases and regulatory framework are presented for these DDI aspects. Also presented is an industry perspective on how to approach these issues in support of drug development. Overall, with the exception of highly permeable and highly soluble (BCS 1) drugs, DDIs related to drug-induced changes in gastrointestinal (GI) physiology can be substantial, thus warranting more attentions. For a better understanding of absorption-associated DDI potential in a clinical setting, mechanistic studies should be conducted based on holistic integration of the pharmaceutical profiles (e.g., pH-dependent solubility) and pharmacological properties (e.g., GI physiology and therapeutic margin) of drug candidates. Although majority of DDI events related to altered plasma protein binding are not expected to be of clinical significance, exceptions exist for a subset of compounds with certain pharmacokinetic and pharmacological properties. Knowledge of the identity of binding proteins and the binding extent in various clinical setting (including disease states) can be valuable in aiding clinical DDI data interpretations, and ensuring safe and effective use of new drugs.

  2. A new preclinical biomarker for risk of Torsades de Pointes: drug-induced reduction of the cardiac electromechanical window.

    PubMed

    Vargas, Hugo M

    2010-12-01

    Evaluation of new therapeutic agents for their potential to cause QT interval prolongation and drug-induced ventricular arrhythmia, like Torsades de Pointes (TdP), is a critical activity during drug development. The QT interval has been used as a surrogate biomarker to assess ventricular repolarization effects caused by drug-induced blockade of cardiac repolarizing currents, mainly IKr, but is imperfect in predicting proarrhythmia. Evidence suggests that left ventricular mechanical dysfunction may also contribute to ventricular arrhythmias; thus, electrical and mechanical alterations may have a role in drug-induced TdP. The electromechanical window (EMw) represents the time difference between the end of electrical systole (i.e. the QT interval) and the completion of ventricular relaxation (i.e. the QLVPend interval), and appears to be a new potential biomarker for TdP risk. A reduction in the EMw (to negative values) has now been shown to be associated with the onset of TdP in an anaesthetized dog model of long QT1 syndrome. Therefore, the EMw represents a novel indicator of TdP risk that may add predictive value beyond assay of drug-induced QT interval prolongation.

  3. [Improvement of intestinal absorption of poorly absorbable drugs by various sugar esters].

    PubMed

    Yamamoto, Akira; Katsumi, Hidemasa; Kusamori, Kosuke; Sakane, Toshiyasu

    2014-01-01

    Effects of sucrose fatty acid esters (sugar esters) on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption of CF from the rat small intestine was significantly enhanced in the presence of various sugar esters and a maximal absorption enhancing effect was observed in the presence of 0.5%(w/v) S-1670. The absorption enhancing effect of S-1670 in the small intestine decreased as the molecular weights of drugs increased. Moreover, we evaluated the intestinal membrane damage with or without various sugar esters. These sugar esters (0.5%(w/v)) did not increase the activities of lactate dehydrogenase (LDH), suggesting that these sugar esters did not cause serious membrane damage to the intestinal epithelium. Furthermore, these sugar esters increased membrane fluidity of lipid layers of the intestinal brush border membranes and decreased the transepithelial electrical resistance (TEER) of Caco-2 cells. Therefore, these findings suggested that these sugar esters might improve the intestinal absorption of poorly absorbable drugs via a transcellular and a paracellular pathways.

  4. The CO2 absorption spectrum in the 2.3 μm transparency window by high sensitivity CRDS: (II) Self-absorption continuum

    NASA Astrophysics Data System (ADS)

    Mondelain, D.; Vasilchenko, S.; Čermák, P.; Kassi, S.; Campargue, A.

    2017-01-01

    The CO2 absorption continuum near 2.3 μm is determined for a series of sub atmospheric pressures (250-750 Torr) by high sensitivity Cavity Ring Down Spectroscopy. An experimental procedure consisting in injecting successively a gas flow of CO2 and synthetic air, keeping constant the gas pressure in the CRDS cell, has been developed. This procedure insures a high stability of the spectra baseline by avoiding changes of the optical alignment due to pressure changes. The CO2 continuum was obtained as the difference between the CO2 absorption coefficient and a local lines simulation using a Voigt profile truncated at ±25 cm-1. Following the results of the preceding analysis of the CO2 rovibrational lines (Vasilchenko S et al. J Quant Spectrosc Radiat Transfer 10.1016/j.jqsrt.2016.07.002, a CO2 line list with intensities obtained by variational calculations and empirical line positions was preferred to the HITRAN line list. A quadratic pressure dependence of the absorption continuum is observed, with an average binary absorption coefficient increasing from 2 to 4×10-8 cm-1 amagat-2 between 4320 and 4380 cm-1. The obtained continuum is found in good agreement with a previous measurement using much higher densities (20 amagat) and a low resolution grating spectrograph and is consistent with values currently used in the analysis of Venus spectra.

  5. Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.

    PubMed

    Tanaka, Akiko; Furubayashi, Tomoyuki; Enomura, Yuki; Hori, Tomoki; Shimomura, Rina; Maeda, Chiaki; Kimura, Shunsuke; Inoue, Daisuke; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2017-01-01

    The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

  6. Fractional kinetics in drug absorption and disposition processes.

    PubMed

    Dokoumetzidis, Aristides; Macheras, Panos

    2009-04-01

    We explore the use of fractional order differential equations for the analysis of datasets of various drug processes that present anomalous kinetics, i.e. kinetics that are non-exponential and are typically described by power-laws. A fractional differential equation corresponds to a differential equation with a derivative of fractional order. The fractional equivalents of the "zero-" and "first-order" processes are derived. The fractional zero-order process is a power-law while the fractional first-order process is a Mittag-Leffler function. The latter behaves as a stretched exponential for early times and as a power-law for later times. Applications of these two basic results for drug dissolution/release and drug disposition are presented. The fractional model of dissolution is fitted successfully to datasets taken from literature of in vivo dissolution curves. Also, the proposed pharmacokinetic model is fitted to a dataset which exhibits power-law terminal phase. The Mittag-Leffler function describes well the data for small and large time scales and presents an advantage over empirical power-laws which go to infinity as time approaches zero. The proposed approach is compared conceptually with fractal kinetics, an alternative approach to describe datasets with non exponential kinetics. Fractional kinetics offers an elegant description of anomalous kinetics, with a valid scientific basis, since it has already been applied in problems of diffusion in other fields, and describes well the data.

  7. Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs Cimetidine and Acyclovir.

    PubMed

    Vaithianathan, Soundarya; Haidar, Sam H; Zhang, Xinyuan; Jiang, Wenlei; Avon, Christopher; Dowling, Thomas C; Shao, Changxing; Kane, Maureen; Hoag, Stephen W; Flasar, Mark H; Ting, Tricia Y; Polli, James E

    2016-02-01

    The objective was to assess the impact of larger than conventional amounts of 14 commonly used excipients on Biopharmaceutics Classification System (BCS) class 3 drug absorption in humans. Cimetidine and acyclovir were used as model class 3 drugs across three separate four-way crossover bioequivalence (BE) studies (n = 24 each) in healthy human volunteers, denoted as study 1A, 1B, and 2. In study 1A and 1B, three capsule formulations of each drug were manufactured, collectively involving 14 common excipients. Capsule formulations that incorporated hydroxypropyl methylcellulose (HPMC) or magnesium stearate exhibited lower absorption. The cimetidine commercial solution contained sorbitol and also resulted in lower absorption. Hence, in study 2, two capsule formulations with lower amounts of HPMC and magnesium stearate, the sorbitol-containing commercial solution, and a sorbitol-free solution were assessed for BE. Overall, 12 common excipients were found in large amounts to not impact BCS class 3 drug absorption in humans, such that these excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather simply be not more than the quantities studied here. Meanwhile, for each HPMC and microcrystalline cellulose, BCS class 3 biowaivers require these two excipients to be qualitatively the same and quantitatively very similar to the reference.

  8. Accurate measurements and temperature dependence of the water vapor self-continuum absorption in the 2.1 μm atmospheric window

    SciTech Connect

    Ventrillard, I.; Romanini, D.; Mondelain, D.; Campargue, A.

    2015-10-07

    In spite of its importance for the evaluation of the Earth radiative budget, thus for climate change, very few measurements of the water vapor continuum are available in the near infrared atmospheric windows especially at temperature conditions relevant for our atmosphere. In addition, as a result of the difficulty to measure weak broadband absorption signals, the few available measurements show large disagreements. We report here accurate measurements of the water vapor self-continuum absorption in the 2.1 μm window by Optical Feedback Cavity Enhanced Absorption Spectroscopy (OF-CEAS) for two spectral points located at the low energy edge and at the center of the 2.1 μm transparency window, at 4302 and 4723 cm{sup −1}, respectively. Self-continuum cross sections, C{sub S}, were retrieved with a few % relative uncertainty, from the quadratic dependence of the spectrum base line level measured as a function of water vapor pressure, between 0 and 16 Torr. At 296 K, the C{sub S} value at 4302 cm{sup −1} is found 40% higher than predicted by the MT-CKD V2.5 model, while at 4723 cm{sup −1}, our value is 5 times larger than the MT-CKD value. On the other hand, these OF-CEAS C{sub S} values are significantly smaller than recent measurements by Fourier transform spectroscopy at room temperature. The temperature dependence of the self-continuum cross sections was also investigated for temperatures between 296 K and 323 K (23-50 °C). The derived temperature variation is found to be similar to that derived from previous Fourier transform spectrometer (FTS) measurements performed at higher temperatures, between 350 K and 472 K. The whole set of measurements spanning the 296-472 K temperature range follows a simple exponential law in 1/T with a slope close to the dissociation energy of the water dimer, D{sub 0} ≈ 1100 cm{sup −1}.

  9. Enhancing drugs absorption through third-degree burn wound eschar.

    PubMed

    Manafi, Ali; Hashemlou, Azadeh; Momeni, Parisa; Moghimi, Hamid R

    2008-08-01

    Antimicrobial therapy remains the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic levels in wound. On the other hand, some topically applied antimicrobials cannot penetrate eschar well enough. Therefore, an attempt has been made here to increase permeation of topically applied drugs through eschar using the so-called skin penetration enhancers. To perform this investigation, effects of different potential penetration enhancers on permeation of chlorhexidine, silver sulfadiazine and nitroglycerin through human third-degree burn eschar was evaluated. Results showed that water, glycerin, saline, sodium lauryl sulphate (SDS) and ethanol tend to reduce permeation of chlorhexidine through burn eschar. But, water, glycerin, hexane:ethanol and ethyl acetate:ethanol were able to increase permeation of silver sulfadiazine significantly by about 1.2-1.8 times, while saline, SDS and dimethyl sulfoxide were not able to change its permeation. Glycine showed 2.7 times enhancement toward permeation of nitroglycerin, followed by water, hexane:ethanol mixture, saline and SDS with enhancement ratios of 1.8-2.3. Urea, ethanol and citral were not able to increase permeation of nitroglycerin through eschar. This study shows that permeation of drugs through burn eschar can be improved by penetration enhancement including hydration; the effect depends on the nature of the penetrant.

  10. Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption

    NASA Astrophysics Data System (ADS)

    Verma, Rajeshwar P.; Hansch, Corwin; Selassie, Cynthia D.

    2007-01-01

    Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials. The present study provides comparative QSAR analysis on PAMPA/modified PAMPA for high throughput profiling of drugs with respect to Caco-2 cells and human intestinal absorption.

  11. Ophthalmic drug delivery utilizing two-photon absorption: a novel approach to treat posterior capsule opacification

    NASA Astrophysics Data System (ADS)

    Kim, H.-C.; Träger, J.; Zorn, M.; Haberkorn, N.; Hampp, N.

    2007-07-01

    Intraocular lens (IOL) implantation is the standard technique to treat cataract. Despite recent progress in surgical procedures, posterior capsule opacification is one of the sill remaining postoperative complications of cataract surgery. We present a novel strategy to reduce the incidence of posterior capsule opacification. A drug delivery polymer suitable for manufacturing intraocular lenses has been developed which enables repeated drug release in a non-invasive and controlled manner. The therapeutic molecules are attached through a UV light sensitive linkage to the polymer backbone which is mainly responsible for the optical properties of the intraocular lenses. However, UV light can not trigger the release of drug from the polymer due to the high absorption of the cornea. We developed linkers which enable drug release by two-photon absorption induced cleavage of the linker structure. Since the two-photon absorption requires high photon densities, this does not occur in ambient light conditions in daily life, but is easily triggered by focused laser beams from a pulsed laser. In this proof-of-principle study we have employed a cyclobutane type linker and investigated the properties of the therapeutic system with the approved drugs 5-fluorouracil and chlorambucil. The controlled drug delivery was successfully demonstrated in vitro and additional cell tests confirmed that the device itself shows no cytotoxicity until photochemical activation. This presented concept can provide a powerful method in ophthalmic drug delivery.

  12. Estimation of drug absorption in antibiotic soaked bone grafts

    PubMed Central

    Shah, Manish Ramesh; Patel, Rukesh R; Solanki, Randhirsinh V; Gupta, Shailendra H

    2016-01-01

    Introduction: There is paucity of literature about antibiotic uptake in bone grafts soaked in antibiotic solutions at room temperature in the operation theatre. We hypothesized that if bone grafts are dipped in different strengths of antibiotic solutions for sufficient period, their utilization at the target site helps in localized release of antibiotics in adequate inhibitory concentration to achieve the bacterial regression. The purpose of the study was to find out: (1) Optimum duration, strength, and volume of antibiotic solution required for dipping bone grafts at room temperature prior to the use. (2) What could be the clinical implications of the results obtained? Materials and Methods: Bone shavings from total knee replacements were processed, frozen and transported to bio-analytical laboratory. The bone fragments were then impregnated with different volume and different strength of gentamicin and vancomycin over different time periods. The soaked bone samples underwent further processing for analysis on liquid chromatography tandem mass spectrometry (LC-MS/MS) system. Results: After series of bio-analytical estimation for the soaked drug concentration among bone fragments; the optimal estimation was found with 0.2 mL of 2% strength of gentamicin and vancomycin, the optimal time was found with soakage up to 30 min. These estimated values of soaked antibiotics were five 5 times higher than required minimal inhibitory concentration (MIC) values for bacterial regression. Conclusion: Use of antibiotic soaked bone allografts at target sites as potential drug carrier can be a hassle- free yet cost- effective and safe process for achieving maximum bacterial regression. PMID:27904224

  13. Concomitant intake of alcohol may increase the absorption of poorly soluble drugs.

    PubMed

    Fagerberg, Jonas H; Sjögren, Erik; Bergström, Christel A S

    2015-01-25

    Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug

  14. Synergistic thermoradiotherapy based on PEGylated Cu3BiS3 ternary semiconductor nanorods with strong absorption in the second near-infrared window.

    PubMed

    Li, Ang; Li, Xiang; Yu, Xujiang; Li, Wei; Zhao, Ruyi; An, Xiao; Cui, Daxiang; Chen, Xiaoyuan; Li, Wanwan

    2017-01-01

    In this work, we report a successful synthesis of copper bismuth sulfide nanorods (NRs) with broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, which can be used as a 1064 nm-laser-driven photothermal agent with the photothermal conversion efficiency of 40.7%, noticeably higher than most of the reported PTT agents working in NIR-II window. The as-prepared PEGylated Cu3BiS3 NRs were used as photoacoustic imaging (PAI) and CT imaging agents due to their strong NIR absorption and large X-ray attenuation coefficient of bismuth. We are the first to demonstrate that a small quantity of PEGylated Cu3BiS3 NRs in tumors can concentrate radiation energy and trigger mild PTT under NIR-II irradiation and thus, these particles could be used as a novel, synergistic thermoradiotheraputic agent that enhances the efficacy of radiotherapy.

  15. Elicitation, a new window into plant chemodiversity and phytochemical drug discovery.

    PubMed

    Poulev, Alexander; O'Neal, Joseph M; Logendra, Sithes; Pouleva, Reneta B; Timeva, Vesa; Garvey, Alison S; Gleba, Doloressa; Jenkins, Ivan S; Halpern, Barbara T; Kneer, Ralf; Cragg, Gordon M; Raskin, Ilya

    2003-06-05

    Plant extracts collected from the wild are important sources for drug discovery. However, these extracts suffer from a lack of reproducible bioactivity and chemical composition caused by the highly inducible, variable, and transitory nature of plant secondary metabolism. Here, we demonstrate that exposing roots of hydroponically grown plants to chemical elicitors selectively and reproducibly induced the production of bioactive compounds, dramatically increased the hit rate, and more than doubled the number of plant species showing in vitro activity against bacteria, fungi, or cancer. Elicitation performed under controlled conditions dramatically improves reliability and efficiency of plant extracts in drug discovery while preserving wild species and their habitats.

  16. The assessment of human regional drug absorption of free acid and sodium salt forms of acipimox, in healthy volunteers, to direct modified release formulation strategy.

    PubMed

    Menon, Rajeev; Cefali, Eugenio; Wilding, Ian; Wray, Heather; Connor, Alyson

    2009-12-01

    Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non-randomized, three-way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediate release capsules, and was not influenced by the form of the drug administered. Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively. Following administration to the colon, the extent of absorption was further reduced. The data indicate that bioavailability from the DSB was limited by the solubility of the drug coupled with an absorption window, whilst absorption from the colon was limited by permeability. The study provided detailed information to support and guide the formulation strategy for a MR form of acipimox, which may improve the treatment of adult patients with type II diabetes and dyslipidemia.

  17. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    NASA Astrophysics Data System (ADS)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  18. Presurgical window of opportunity trial design as a platform for testing anticancer drugs: Pros, cons and a focus on breast cancer.

    PubMed

    Maugeri-Saccà, Marcello; Barba, Maddalena; Vici, Patrizia; Pizzuti, Laura; Sergi, Domenico; Catenaro, Teresa; Di Lauro, Luigi; Mottolese, Marcella; Santini, Daniele; Milella, Michele; De Maria, Ruggero

    2016-10-01

    The high attrition rate is a major issue in anticancer drug development. Among the alternative trial designs, presurgical window of opportunity trials envision a short course treatment in the time window between diagnostic biopsy and surgery in a moderately-sized patient population. This approach allows testing therapeutics when pre- and post-treatment tumor tissues are available for comprehensive molecular analyses. The emerging evidence may help define the ability of a given agent to modulate its target(s) and help obtain a broader picture of the molecular changes operated by the treatment. The resulting gain may outweigh the potential harms for patients in the early disease setting. Window of opportunity trials have been extensively applied to breast cancer. Overall, a wider use of these trial designs might lead to the identification of potential responders, ineffective drugs or combinations, and ultimately contribute to enhance the efficiency of the clinical developmental process.

  19. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    PubMed

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  20. Drug marker absorption in relation to pellet size, gastric motility and viscous meals in humans

    NASA Technical Reports Server (NTRS)

    Rhie, J. K.; Hayashi, Y.; Welage, L. S.; Frens, J.; Wald, R. J.; Barnett, J. L.; Amidon, G. E.; Putcha, L.; Amidon, G. L.

    1998-01-01

    PURPOSE: The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. METHODS: Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p < 0.01). CONCLUSIONS: The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

  1. Water vapor absorption into amorphous hydrophobic drug/poly(vinylpyrrolidone) dispersions.

    PubMed

    Crowley, Kieran J; Zografi, George

    2002-10-01

    Water vapor absorption isotherms were measured for three amorphous hydrophobic drug/poly(vinylpyrrolidone) (PVP) dispersions in the concentration range 10-90% w/w PVP. Experimental isotherms were compared to predicted isotherms calculated using each individual component isotherm multiplied by its weight fraction. Indomethacin (IMC)/PVP, ursodeoxycholic acid (UDCA)/PVP and indapamide (IDP)/PVP amorphous dispersions all exhibited experimental isotherms reduced relative to predicted isotherms indicating that dispersion formation altered the water vapor absorption properties of the individual components. For all three drug/PVP systems, deviation from predicted water uptake was greatest close to the 1:1 drug:PVP monomer composition, indicating that intermolecular interaction in amorphous dispersions affects the water uptake properties of the individual components. Using dry glass transition temperature (T(g)) data, the extent of drug/PVP interaction was shown to be greatest in the IDP/PVP system, which could explain why the largest reduction in water vapor absorption was found in this system. The plasticizing effect of absorbed water varied according to dry dispersion PVP content in all systems and the resulting nonideal changes in free volume, calculated using the Vrentas model, were greatest close to the 1:1 drug:PVP monomer composition. A three-component Flory-Huggins model successfully predicted isotherms for IMC/PVP compositions from 60 to 90% w/w PVP and identified an IMC-PVP interaction parameter chi in the range 1.27-1.49, values that suggest poor homogeneity of mixing in the dry system. These data indicate that amorphous dispersion formation causes both chemical and physical changes in the individual amorphous components that can have a significant effect on their water vapor absorption properties.

  2. Investigation of new acyloxy derivatives of cholic acid and their esters as drug absorption modifiers.

    PubMed

    Mrózek, Lech; Dvořáková, Lenka; Mandelová, Zuzana; Rárová, Lucie; Řezáčová, Anna; Plaček, Lukáš; Opatřilová, Radka; Dohnal, Jiří; Paleta, Oldřich; Král, Vladimír; Drašar, Pavel; Jampílek, Josef

    2011-01-01

    Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. Intestinal absorption promoters/enhancers are used as excipients in oral formulations of poorly oral-bioavailable drugs. Series of fourteen acyloxy derivatives of 5β-cholic acid as potential drug absorption modifiers was generated by multistep synthesis. The synthesis of all newly prepared compounds is presented here. Structure confirmation of all generated compounds was accomplished by (1)H NMR, (13)C NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R(M)) was determined. The hydrophobicity (logP) and solubility (logS) of the studied compounds were also calculated using two commercially available programs. All the target compounds were tested for their in vitro transdermal penetration activity and as potential intestinal absorption enhancers. The anti-proliferative activity of all the final compounds was also assessed against the human cancer cell lines: T-lymphoblastic leukemia cell line and the breast adenocarcinoma cell line. Their cytotoxicity was also evaluated against the normal human skin fibroblast cells. Two compounds showed anti-proliferative effect on cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC(50)>37 μM), indicating they would have low cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effects are discussed in this article.

  3. Probabilistic modeling of percutaneous absorption for risk-based exposure assessments and transdermal drug delivery.

    SciTech Connect

    Ho, Clifford Kuofei

    2004-06-01

    Chemical transport through human skin can play a significant role in human exposure to toxic chemicals in the workplace, as well as to chemical/biological warfare agents in the battlefield. The viability of transdermal drug delivery also relies on chemical transport processes through the skin. Models of percutaneous absorption are needed for risk-based exposure assessments and drug-delivery analyses, but previous mechanistic models have been largely deterministic. A probabilistic, transient, three-phase model of percutaneous absorption of chemicals has been developed to assess the relative importance of uncertain parameters and processes that may be important to risk-based assessments. Penetration routes through the skin that were modeled include the following: (1) intercellular diffusion through the multiphase stratum corneum; (2) aqueous-phase diffusion through sweat ducts; and (3) oil-phase diffusion through hair follicles. Uncertainty distributions were developed for the model parameters, and a Monte Carlo analysis was performed to simulate probability distributions of mass fluxes through each of the routes. Sensitivity analyses using stepwise linear regression were also performed to identify model parameters that were most important to the simulated mass fluxes at different times. This probabilistic analysis of percutaneous absorption (PAPA) method has been developed to improve risk-based exposure assessments and transdermal drug-delivery analyses, where parameters and processes can be highly uncertain.

  4. Rationale for ibuprofen co-administration with antacids: potential interaction mechanisms affecting drug absorption.

    PubMed

    Parojcić, Jelena; Corrigan, Owen I

    2008-06-01

    Ibuprofen is a widely used NSAID which is often co-administered with antacids because of its gastro-irritant effects. Literature data suggest that antacid interactions may increase or decrease the drug's absorption rate and onset of action and that the interaction may be formulation specific. In the present study, literature data on ibuprofen absorption were evaluated in order to gain insight into the nature of the in vivo effect. Solubility determinations in reactive media containing magnesium or aluminium and dissolution studies in the presence of antacid suspension were performed in an attempt to simulate in vitro the effects observed in vivo. The results obtained indicate that magnesium hydroxide enhances ibuprofen solubility, dissolution and bioavailability, while aluminium hydroxide has a retarding effect. Solubility studies indicated formation of a soluble solid ibuprofen phase in the presence of Mg2+, in contrast, an insoluble ibuprofen salt was formed with Al3+. The introduction of magnesium based antacid suspension into the dissolution media resulted in a formulation specific increase in drug dissolution rate with the most pronounced effect observed for the slowest release tablet formulation. The results obtained indicate the potential for in vitro studies to predict physicochemical interactions that are likely to influence drug absorption rate in vivo.

  5. Ultrasound-aided microbubbles facilitate the delivery of drugs to the inner ear via the round window membrane.

    PubMed

    Shih, Cheng-Ping; Chen, Hsin-Chien; Chen, Hang-Kang; Chiang, Min-Chang; Sytwu, Huey-Kang; Lin, Yi-Chun; Li, Shiue-Li; Shih, Yu-Fan; Liao, Ai-Ho; Wang, Chih-Hung

    2013-04-28

    The round window membrane (RWM) acts as a barrier between the middle ear and cochlea and can serve as a crucial route for therapeutic medications entering the inner ear via middle ear applications. In this study, we targeted the practical application of microbubbles (MBs) ultrasound on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear. Using biotin-fluorescein isothiocyanate conjugates (biotin-FITC) as delivery agents and guinea pig animal models, we showed that MB ultrasound exposure can improve the inner ear system use of biotin-FITC delivery via the RWM by approximately 3.5 to 38 times that of solely soaking biotin-FITC around the RWM for spontaneous diffusion. We also showed that there was significant enhancement of hair cell uptake of gentamicin in animals whose tympanic bullas were soaked with MB-mixed gentamicin-Texas Red or gentamicin and exposed to ultrasound. Furthermore, increased permeability of the RWM from acoustic cavitation of MBs could also be visualized immediately following ultrasound exposure by using Alexa Fluor 488-conjugated phalloidin as a tracer. Most importantly, such applications had no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds assessed by auditory brainstem responses. We herein provide a basis for MB ultrasound-mediated techniques with therapeutic medication delivery to the inner ear for future application in humans.

  6. Two-photon absorption-induced drug delivery from polymers for medical applications

    NASA Astrophysics Data System (ADS)

    Kim, Hee-Cheol; Kreiling, Stefan; Haertner, Sebastian; Hesse, Lutz; Greiner, Andreas; Hampp, Norbert A.

    2004-06-01

    Novel polymeric materials carrying a drug depot have been developed which are suitable for fabrication of photochemically modulated drug delivery devices. In order to avoid uncontrolled drug release the drug is covalently attached to the polymer backbone using a photo-active linker. Controlled drug release from the polymer can be accomplished either via single-photon excitation or by two-photon absorption (TPA). In particular the second possibility is of interest for applications where exposure to day light or UV light may not be omitted. One example are polymeric intraocular lenses (IOL), which are implanted instead of the opaque natural lens during cataract surgery. Secondary cataract formation is quite often observed after implantation of polymeric IOLs. In this study the well known cell toxic agent 5-fluorouracil (5FU) attached to a methylmethacrylate-based polymer was investigated as an IOL which can upon photochemical excitation release 5FU in order to treat or to prevent secondary cataract formation. The photochemical cleavage of the linker molecule was analyzed with single- and two-photon excitation. UV/VIS spectroscopy and HPLC analysis confirmed the release of 5FU form the polymer backbone. The diffusion of the drug precursor out from the polymer as well as the hydrolysis of the drug precursor which leads to 5FU formation were investigated in vitro.

  7. The absorption spectrum of water vapor in the 2.2 μm transparency window: High sensitivity measurements and spectroscopic database

    NASA Astrophysics Data System (ADS)

    Campargue, A.; Mikhailenko, S. N.; Vasilchenko, S.; Reynaud, C.; Béguier, S.; Čermák, P.; Mondelain, D.; Kassi, S.; Romanini, D.

    2017-03-01

    The weak absorption spectrum of water vapor in the important 2.2 μm transparency window is investigated with very high sensitivity. Overall, about 400 absorption lines were measured by Cavity Ring Down Spectroscopy (CRDS) and Optical-Feedback-Cavity Enhanced Laser Spectroscopy (OF-CEAS) in five spectral intervals: 4248.2-4257.3, 4298.4-4302.6, 4336.8.5-4367.5, 4422.4-4441.2 and 4514.6-4533.7 cm-1. The achieved sensitivity of the recordings (noise equivalent absorption, αmin, on the order of 2×10-10 cm-1) allowed detecting transitions with intensity values down to 1×10-28 cm/molecule, more than one order of magnitude better than previous studies by Fourier Transform spectroscopy. The rovibrational assignment was performed on the basis of variational calculations and of previously determined empirical energy values. Most of the newly assigned lines correspond to transitions of the ν1, ν3 and 3ν2 bands of H217O in natural isotopic abundance. Fourteen energy levels of H217O, H218O and HD18O are newly determined. An accurate and complete spectroscopic database is constructed for natural water in the 4190-4550 cm-1 region (2.39-2.20 μm). The list includes about 4500 transitions with intensity greater than 1×10-29 cm/molecule, for the six most abundant isotopologues in natural isotopic abundance. Line positions were obtained by difference of empirical energy values determined from literature data and complemented with the present CRDS results. The list is made mostly complete by including weak transitions not yet detected, with positions calculated from empirical levels and variational intensities. The variational intensities computed by a collaboration between the University College London and the Institute of Applied Physics in Nizhny Novgorod are found to improve significantly previous results by Schwenke and Partridge. Examples of comparison of the constructed line list to CRDS spectra and to simulations based on the HITRAN2012 list illustrate the advantages

  8. Lipid-based formulations and drug supersaturation: harnessing the unique benefits of the lipid digestion/absorption pathway.

    PubMed

    Williams, Hywel D; Trevaskis, Natalie L; Yeap, Yan Yan; Anby, Mette U; Pouton, Colin W; Porter, Christopher J H

    2013-12-01

    Drugs with low aqueous solubility commonly show low and erratic absorption after oral administration. Myriad approaches have therefore been developed to promote drug solubilization in the gastrointestinal (GI) fluids. Here, we offer insight into the unique manner by which lipid-based formulations (LBFs) may enhance the absorption of poorly water-soluble drugs via co-stimulation of solubilization and supersaturation. Supersaturation provides an opportunity to generate drug concentrations in the GI tract that are in excess of the equilibrium crystalline solubility and therefore higher than that achievable with traditional formulations. Incorporation of LBF into lipid digestion and absorption pathways provides multiple drivers of supersaturation generation and the potential to enhance thermodynamic activity and absorption. These drivers include 1) formulation dispersion, 2) lipid digestion, 3) interaction with bile and 4) lipid absorption. However, high supersaturation ratios may also stimulate drug precipitation and reduce exposure where re-dissolution limits absorption. The most effective formulations are likely to be those that generate moderate supersaturation and do so close to the site of absorption. LBFs are particularly well suited to these criteria since solubilization protects against high supersaturation ratios, and supersaturation initiation typically occurs in the small intestine, at the absorptive membrane.

  9. Assessment of absorption potential of poorly water-soluble drugs by using the dissolution/permeation system.

    PubMed

    Kataoka, Makoto; Yano, Koji; Hamatsu, Yoriko; Masaoka, Yoshie; Sakuma, Shinji; Yamashita, Shinji

    2013-11-01

    This study aims to assess the absorption potential of oral absorption of poorly water-soluble drugs by using the dissolution/permeation system (D/P system). The D/P system can be used to perform analysis of drug permeation under dissolution process and can predict the fraction of absorbed dose in humans. When celecoxib at 1/100 of a clinical dose was applied to the D/P system, percentage of dose dissolved and permeated significantly decreased with an increase in the applied amount, resulting in the oral absorption being predicted to be 22-55%. Whereas similar dissolution and permeation profiles of montelukast sodium were observed, estimated absorption (69-85%) was slightly affected. Zafirlukast absorption (33-36%) was not significantly affected by the dose, although zafirlukast did not show complete dissolution. The relationship between clinical dose and predicted oral absorption of drugs corresponded well to clinical observations. The limiting step of the oral absorption of celecoxib and montelukast sodium was solubility, while that of zafirlukast was dissolution rate. However, due to high permeability of montelukast, oral absorption was not affected by dose. Therefore, the D/P system is a useful tool to assess the absorption potential of poorly water-soluble drugs for oral use.

  10. Excipient effects on gastrointestinal transit and drug absorption in beagle dogs.

    PubMed

    Schulze, Julia D R; Peters, Erin E; Vickers, Ann W; Staton, J Scott; Coffin, Mark D; Parsons, Gary E; Basit, Abdul W

    2005-08-26

    Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.

  11. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review

    PubMed Central

    Batchelor, Hannah K.

    2015-01-01

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food–drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food–drug interactions within paediatric populations. PMID:27417362

  12. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review.

    PubMed

    Batchelor, Hannah K

    2015-06-09

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food-drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food-drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food-drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food-drug interactions within paediatric populations.

  13. High-performance dispersive Raman and absorption spectroscopy as tools for drug identification

    NASA Astrophysics Data System (ADS)

    Pawluczyk, Olga; Andrey, Sam; Nogas, Paul; Roy, Andrew; Pawluczyk, Romuald

    2009-02-01

    Due to increasing availability of pharmaceuticals from many sources, a need is growing to quickly and efficiently analyze substances in terms of the consistency and accuracy of their chemical composition. Differences in chemical composition occur at very low concentrations, so that highly sensitive analytical methods become crucial. Recent progress in dispersive spectroscopy with the use of 2-dimensional detector arrays, permits for signal integration along a long (up to 12 mm long) entrance slit of a spectrometer, thereby increasing signal to noise ratio and improving the ability to detect small concentration changes. This is achieved with a non-scanning, non-destructive system. Two different methods using P&P Optica high performance spectrometers were used. High performance optical dispersion Raman and high performance optical absorption spectroscopy were employed to differentiate various acetaminophen-containing drugs, such as Tylenol and other generic brands, which differ in their ingredients. A 785 nm excitation wavelength was used in Raman measurements and strong Raman signals were observed in the spectral range 300-1800 cm-1. Measurements with the absorption spectrometer were performed in the wavelength range 620-1020 nm. Both Raman and absorption techniques used transmission light spectrometers with volume phase holographic gratings and provided sufficient spectral differences, often structural, allowing for drug differentiation.

  14. Optimization of the Caco-2 permeability assay to screen drug compounds for intestinal absorption and efflux.

    PubMed

    Press, Barry

    2011-01-01

    In vitro permeability assays are a valuable tool for scientists during lead compound optimization. As a majority of discovery projects are focused on the development of orally bioavailable drugs, correlation of in vitro permeability data to in vivo absorption results is critical for understanding the structural-physicochemical relationship (SPR) of drugs exhibiting low levels of absorption. For more than a decade, the Caco-2 screening assay has remained a popular, in vitro system to test compounds for both intestinal permeability and efflux liability. Despite advances in artificial membrane technology and in silico modeling systems, drug compounds still benefit from testing in cell-based epithelial monolayer assays for lead optimization. This chapter provides technical information for performing and optimizing the Caco-2 assay. In addition, techniques are discussed for dealing with some of the most pressing issues surrounding in vitro permeability assays (i.e., low aqueous solubility of test compounds and low postassay recovery). Insights are offered to help researchers avoid common pitfalls in the interpretation of in vitro permeability data, which can often lead to the perception of misleading results for correlation to in vivo data.

  15. Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system

    PubMed Central

    Lee, Dae Ro; Ho, Myoung Jin; Jung, Hyuck Jun; Cho, Ha Ra; Park, Jun Seo; Yoon, Suk-Hyun; Choi, Yong Seok; Choi, Young Wook; Oh, Chung-Hun; Kang, Myung Joo

    2016-01-01

    A new Soluplus (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supersaturable system (S-SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those of conventional SEDDS formulas containing four times greater content of vehicle components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded microemulsion <70 nm in size when in contact with aqueous medium. In an in vitro dissolution test in a nonsink condition, the amphiphilic polymer noticeably retarded drug precipitation and maintained >80% of accumulated dissolution rate for 24 hours, analogous to that from conventional SEDDS. Moreover, pharmacokinetic parameters of the maximum blood concentration and area under the curve from S-SEDDS formula in rats were not statistically different (P>0.05) than those of conventional SEDDS. The results suggest that the Soluplus-based supersaturable system can be an alternative to achieve a comparable in vitro dissolution profile and in vivo oral absorption with conventional SEDDS, with minimal use of vehicle ingredients. PMID:27051286

  16. Amorphous Solid Dispersions or Prodrugs: Complementary Strategies to Increase Drug Absorption.

    PubMed

    Rumondor, Alfred C F; Dhareshwar, Sundeep S; Kesisoglou, Filippos

    2016-09-01

    Maximizing oral bioavailability of drug candidates represents a challenge in the pharmaceutical industry. In recent years, there has been an increase in the use of amorphous solid dispersions (ASDs) to address this issue, where a growing number of solid dispersion formulations have been introduced to the market. However, an increase in solubility or dissolution rate through ASD does not always result in sufficient improvement of oral absorption because solubility limitations may still exist at high doses. Chemical modification in the form of a prodrug may offer an alternative approach for these cases. Although prodrugs have been primarily used to improve membrane permeability, examples are available in which prodrugs have been used to increase drug solubility beyond what can be achieved via formulation approaches. In this mini review, the role of ASDs and prodrugs as 2 complementary approaches in improving oral bioavailability of drug candidates is discussed. We discuss the fundamental principles of absorption and bioavailability, and review available literature on both solid dispersions and prodrugs, providing a summary of their use and examples of successful applications, and cover some of the biopharmaceutics evaluation aspects for these approaches.

  17. New propanoyloxy derivatives of 5β-cholan-24-oic acid as drug absorption modifiers.

    PubMed

    Coufalová, Lenka; Mrózek, Lech; Rárová, Lucie; Plaček, Lukáš; Opatřilová, Radka; Dohnal, Jiří; Král'ová, Katarína; Paleta, Oldřich; Král, Vladimír; Drašar, Pavel; Jampílek, Josef

    2013-05-01

    A series of final twelve propanoyloxy derivatives of 5β-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by 1H NMR, 13C NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (RM) was determined. The hydrophobicity (log P), solubility (log S), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukemia cell line and breast adenocarcinoma cell line. One compound showed selective cytotoxicity against human skin fibroblast cells and another compound possessed the highest cytotoxicity against all the tested cell lines. Only one compound expressed anti-proliferative effect on leukemia cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50>37 μM), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effect are discussed in this article.

  18. New polyfluorothiopropanoyloxy derivatives of 5β-cholan-24-oic acid designed as drug absorption modifiers.

    PubMed

    Mrózek, Lech; Coufalová, Lenka; Rárová, Lucie; Plaček, Lukáš; Opatřilová, Radka; Dohnal, Jiří; Kráľová, Katarína; Paleta, Oldřich; Král, Vladimír; Drašar, Pavel; Jampílek, Josef

    2013-09-01

    A series of final six propanoyloxy derivatives of 5β-cholan-24-oic acid (tridecafluoroctylsulfanyl- and tridecafluoroctylsulfinylethoxycarbonylpropanoyloxy derivatives) as potential drug absorption promoters (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by (1)H NMR, (13)C NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (RM) was determined. The hydrophobicity (log P), solubility (logS), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukaemia cell line and breast adenocarcinoma cell line. One compound showed high selective cytotoxicity against human skin fibroblast cells and another compound possessed high cytotoxicity against breast adenocarcinoma cell line and skin fibroblast cells. Only one compound expressed anti-proliferative effect on leukaemia and breast adenocarcinoma cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50>37μM), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and penetration enhancement effect are discussed in this article.

  19. Influence of pH on Drug Absorption from the Gastrointestinal Tract: A Simple Chemical Model

    NASA Astrophysics Data System (ADS)

    Hickman, Raymond J. S.; Neill, Jane

    1997-07-01

    A simple model of the gastrointestinal tract is obtained by placing ethyl acetate in contact with water at pH 2 and pH 8 in separate test tubes. The ethyl acetate corresponds to the lipid material lining the tract while the water corresponds to the aqueous contents of the stomach (pH 2) and intestine (pH 8). The compounds aspirin, paracetamol and 3-aminophenol are used as exemplars of acidic, neutral and basic drugs respectively to illustrate the influence which pH has on the distribution of each class of drug between the aqueous and organic phases of the model. The relative concentration of drug in the ethyl acetate is judged by applying microlitre-sized samples of ethyl acetate to a layer of fluorescent silica which, after evaporation of the ethyl acetate, is viewed under an ultraviolet lamp. Each of the three drugs, if present in the ethyl acetate, becomes visible as a dark spot on the silica layer. The observations made in the model system correspond well to the patterns of drug absorption from the gastrointestinal tract described in pharmacology texts and these observations are convincingly explained in terms of simple acid-base chemistry.

  20. Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery.

    PubMed

    Förster, Matthias; Bolzinger, Marie-Alexandrine; Fessi, Hatem; Briançon, Stephanie

    2009-01-01

    Percutaneous penetration/permeation is a useful tool for obtaining qualitative and/or quantitative information on the amount of a drug, a cosmetic substance, or any chemical that may enter a skin compartment or the systemic circulation of the human body for pharmaceutical or cosmetic purposes, or for toxicological studies. In the latter case, the extent entering can then be taken into consideration in order to calculate the margin of safety using the NOAEL (No Observed Adverse Effect Level) of an appropriate repeated dose toxicity study with the respective substance. This paper is a short overview of various aspects of skin penetration/permeation of drugs or cosmetic agents. The literature reports numerous studies on skin structure and skin properties influencing drug/cosmetic agent permeation profiles and kinetic parameters. The extensive research concerning the skin structure for determining the key parameters of the penetration/permeation process is therefore described first. Mathematical models of the skin absorption process for a drug are then discussed. Finally new developments in pharmaceutical and cosmetic fields to enhance drug permeation or to modify the stratum corneum structure are considered.

  1. Determination of toxic metals in some herbal drugs through atomic absorption spectroscopy.

    PubMed

    Hina, Bushra; Rizwani, Ghazala Hafeez; Naseem, Shahid

    2011-07-01

    This study presents a picture of occurrence of heavy metals (Pb, Cd, Cu, Cr, Co, Fe, Ni, Zn) in some selected valuable herbal drugs (G. glabra, O. bracteatum, V. odorata , F. vulgare, C. cyminum, C. sativum, and Z. officinalis) purchased from three different zones (southern, eastern, and western) of Karachi city using atomic absorption spectrophotometer. Heavy metal concentrations in these drugs were found in the range of: 3.26-30.46 for Pb, 1.6-4.91 for Cd, 0.65-120.21 for Cu, 83.74-433.76 for Zn, 1.61-186.75 for Cr, 0.48-76.97 for Ni, 5.54-77.97 for Co and 65.68-1652.89 µg/g for Fe. Percentage of heavy metals that were found beyond the permissible limits were: 71.4% for Pb, 28.51% for Cd, 14.2% for Cu, and 9.5 % for Cr. Significant difference was noticed for each heavy metal among herbal drugs as well as their zones of collection using two way ANOVA followed by least significant (LSD) test at p<0.05.Purpose of this research is to detect each type of heavy metal contaminant of herbal drugs by environmental pollution, as well as to highlight the health risks associated with the use of such herbal drugs that contain high levels of toxic heavy metals.

  2. Site of drug absorption after oral administration: assessment of membrane permeability and luminal concentration of drugs in each segment of gastrointestinal tract.

    PubMed

    Masaoka, Yoshie; Tanaka, Yusuke; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji

    2006-11-01

    This study was conducted to assess the site of drug absorption in the gastrointestinal (GI) tract after oral administration. Drug permeability to different regions of rat intestine, jejunum, ileum and colon, was measured by in situ single-pass perfusion method. It was revealed that the epithelial surface area should not be a determinant of the regional difference in the intestinal permeability of highly permeable drugs. Effects of the mucus layer at the surface of the epithelium and the fluidity of the epithelial cell membrane on the drug permeability were investigated. These factors are demonstrated to contribute to the regional differences in intestinal drug permeability. The luminal drug concentration in each segment of the GI tract after oral administration was measured directly in fasted rats. Water ingested orally was absorbed quickly in the jejunum and the luminal fluid volume was diminished in the middle to lower part of the small intestine. According to the absorption of water luminal concentration of atenolol, a drug with low permeability, was elevated and exceeded the initial dose concentration. In contrast, the concentration of highly permeable drugs, antipyrine and metoprolol, decreased quickly in the upper part of the intestine and a significant amount of drugs was not detected in the lower jejunum and the ileum. From the time-profiles of luminal drug concentration, fraction of dose absorbed from each segment of the GI tract was calculated. Both antipyrine and metoprolol were found to be absorbed quickly at the upper part of the small intestine. In addition, the possible contribution of gastric absorption was demonstrated for these drugs. The pattern of site-dependent absorption of atenolol showed the higher absorbability in the middle and lower portion of the jejunum. These informations on site-dependent absorption of drugs are considered to be important for effective oral delivery systems.

  3. The rule of unity for human intestinal absorption 2: application to pharmaceutical drugs that are marketed as salts.

    PubMed

    Patel, Raj B; Admire, Brittany; Yalkowsky, Samuel H

    2015-01-01

    The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA <0.5) and those that are well absorbed (FA ≥ 0.5). Inspection of the data as well as a receiver operative characteristic (ROC) plot shows that a single critical MAP value can be used for predicting efficient human absorption of drugs. This forms the basis of a simple rule of unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

  4. Window insulator

    SciTech Connect

    Nesbitt, W. A.

    1985-10-01

    An insulator for mounting to a window. A pair of plastic layers including a plurality of partitions positioned therebetween form air pockets between the layers. A plurality of suction cups and suction grooves arranged in rows on one outer surface of the sheet removably secure the sheet to a window. The sheet includes a circumferentially extending recessed portion receiving the window frame.

  5. Synchrotron radiation and long path cryogenic cells: New tools and results for modelling SF6 absorption in the 10μm atmospheric window

    NASA Astrophysics Data System (ADS)

    Faye, Mbaye; Boudon, Vincent; Loete, Michel; Roy, Pascale; Manceron, Laurent

    2015-04-01

    Sulfur hexa?uoride (SF6) is a heavy and stable molecule used in many sectors, such as the electrical industry, but also as a gas tracer to model air masse motions in the Earth atmosphere. This anthropogenic species is also an atmospheric pollutant owing to its greenhouse effect capability. Although its six fundamental modes have been largely studied up to now, it is not the case for the numerous hot bands that represent the most important part of the SF6 spectrum at room temperature. So, to model correctly the SF6 atmospheric absorption requires the knowledge of the spectroscopic parameters of all states involved in these hot bands. Nevertheless, due to their overlapping, a direct analysis of the hot bands near the 10,5μm absorption of SF6 in the atmospheric window is not possible. It is necessary to use another strategy, gathering information in the far and mid infrared regions on initial and final states to recompute the relevant total absorption. Here, we present new results of an analysis of spectra recorded at the AILES beam line at the SOLEIL Synchrotron facility. For these measurements, we used a IFS125HR interferometer in the 100 - 3200 cm-1 range, coupled to a cryogenic multiple pass cell [1]. The optical path length was adjusted to 93m; the SF6 sample was cooled down to 153 K. We could record 17 rovibrational bands of SF6 in this region with a resolution of 0.0025 cm-1. These results allowed us to perform the detailed analysis of several bands. Adding to previous knowledge on ν3, ν2, 2ν3 and new results on 3ν3, 2ν1 + ν3, ν1 + ν3, ν2 + ν3, ν3 - ν2 , ν3 - ν1 , we developed a global fit of the ν1, ν2, ν3 parameters, thus permitting the modelling of the ν3 + ν1 - ν1, ν3 + ν2 - ν2 hot bands. New information has also been obtained on ν6 and ν3 + ν5 and another strategy will be detailed to model the more important ν3 + ν5 - ν5 and ν3 + ν6 - ν6 hot band contributions. Including these new parameters in the XTDS model [2], we

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

    PubMed

    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 < 0.149 × 10(-4) cm/s) showed 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

  7. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.

    PubMed

    Yan, Chengyun; Gu, Jiwei; Lv, Yuguang; Shi, Weiguo; Jing, Hongying

    2017-03-16

    In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1-1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1-0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.

  8. Determination of platinum originated from antitumoral drugs in human urine by atomic absorption spectrometric methods.

    PubMed

    da Costa, Anilton Coelho; Vieira, Mariana Antunes; Luna, Aderval Severino; de Campos, Reinaldo Calixto

    2010-10-15

    Cisplatin and carboplatin are the most common platinum-based drugs used in cancer treatment. Pharmacokinetic investigations, the evaluation of the body burden during the treatment, as well as baseline levels of platinum in humans have attracted great interest. Thus, accurate analytical methods for fast and easy Pt monitoring in clinical samples become necessary. In the present study atomic absorption spectrometric methods for the determination of platinum in the forms of cisplatin and carboplatin in human urine were investigated. Platinum, in these different forms, could be determined in urine, after simple sample dilution. Regarding electrothermal atomic absorption spectrometry, the optimum parameters were defined by a central composite design optimization. Multiplicative matrix effects were overcome by using a mixture of HCl and NaCl as modifier. The limit of detection (LOD) was 0.004 mgL(-1) of platinum in the original sample. For the analysis of more concentrated samples, high resolution continuous source flame atomic absorption spectrometry was also investigated. Flame conditions were optimized by a multivariate D-optimal design, using as response the sum of the analyte addition calibration slopes and their standard deviations. Matrix matched external calibration with PtCl(2) calibration solutions, was possible, and the LOD was 0.06 mgL(-1) in the original sample. The results obtained by the proposed procedures were also in good agreement with those obtained by an independent comparative procedure.

  9. The effects of microRNA on the absorption, distribution, metabolism and excretion of drugs

    PubMed Central

    He, Y; Chevillet, J R; Liu, G; Kim, T K; Wang, K

    2015-01-01

    The importance of genetic factors (e.g. sequence variation) in the absorption, distribution, metabolism, excretion (ADME) and overall efficacy of therapeutic agents is well established. Our ability to identify, interpret and utilize these factors is the subject of much clinical investigation and therapeutic development. However, drug ADME and efficacy are also heavily influenced by epigenetic factors such as DNA/histone methylation and non-coding RNAs [especially microRNAs (miRNAs)]. Results from studies using tools, such as in silico miRNA target prediction, in vitro functional assays, nucleic acid profiling/sequencing and high-throughput proteomics, are rapidly expanding our knowledge of these factors and their effects on drug metabolism. Although these studies reveal a complex regulation of drug ADME, an increased understanding of the molecular interplay between the genome, epigenome and transcriptome has the potential to provide practically useful strategies to facilitate drug development, optimize therapeutic efficacy, circumvent adverse effects, yield novel diagnostics and ultimately become an integral component of personalized medicine. PMID:25296724

  10. Quantitation of a novel metalloporphyrin drug in plasma by atomic absorption spectroscopy.

    PubMed

    Hoffman, K L; Feng, M R; Rossi, D T

    1999-03-01

    A bioanalytical method to quantify cobalt mesoporphyrin (CoMP), a novel therapeutic agent, in plasma has been developed and validated. The approach involves atomic absorption spectroscopy to determine total cobalt in a sample and a back-calculation of the amount of compound present. Endogenous plasma cobalt concentrations were small ( <0.2 ng/ml(-1) Co in rat plasma) in comparison to the quantitation limit (4.5 ng/ml(-1) Co). The inter-day imprecision of the method was 10.0% relative standard deviation (RSD) and the inter-day bias was +/- 8.0% relative error (RE) over a standard curve range of 4.5- 45.0 ng/ml(-1) Co. Because it quantifies total cobalt, the method cannot differentiate between parent drug and metabolites, but negligible metabolism allows reliable estimates of the actual parent drug concentration. A correlation study between the atomic absorption method and 14C-radiometry demonstrated excellent agreement (r = 0.9868, slope = 1.041 +/- 0.028, intercept = 223.7 +/- 190.0) and further substantiated the accuracy of the methods. Methodology was successfully applied to a pharmacokinetic study of CoMP in rat, with pharmacokinetic parameter estimation. The elimination half-lives, after intra-muscular and subcutaneous administration, were 7.7 and 8.8 days, respectively.

  11. Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism.

    PubMed

    Sugano, Kiyohiko

    2010-10-04

    The aqueous boundary layer (ABL) affects various aspects of oral absorption of a drug, from dissolution of the drug to the apparent K(m) value of intestinal wall metabolism and carrier mediated transport. However, the importance of ABL has often been entirely ignored in oral absorption investigation. In this minireview, the effect of ABL on oral absorption of a drug is discussed in an easy-to-understand manner. This review starts with an introduction of the boundary layer theory with many illustrations (and links to public web movies visualizing the ABL), and then discusses some specific cases of interest in pharmaceutical science, such as dissolution of floating drug particles in the USP paddle apparatus. The effect of the boundary layer on the membrane permeation is also discussed from the viewpoint of structure permeability relationship, carrier mediated transport/metabolism and estimation of the fraction of a dose absorbed for poor solubility compounds.

  12. Effect of abdominal surgery on the intestinal absorption of lipophilic drugs: possible role of the lymphatic transport.

    PubMed

    Gershkovich, Pavel; Itin, Constantin; Yacovan, Avihai; Amselem, Shimon; Hoffman, Amnon

    2009-06-01

    Although abdominal surgery is a routine procedure in clinical practice and in preclinical investigation, little is known regarding its effect on the intestinal absorption of drugs. The aim of this study was to investigate the effect of abdominal surgery on the intestinal absorption of highly lipophilic compounds with different absorption mechanisms following oral administration. The 2 compounds that were tested were biopharmaceutical classification system (BCS) class 2 model lipophilic cannabinoid derivatives, dexanabinol and PRS-211,220. Although dexanabinol is mostly absorbed via passive diffusion to the portal blood, PRS-211,220 is absorbed mostly via lymphatic transport. In this work, we compared the absorption of these compounds after abdominal surgery in rat with the absorption data obtained from naïve animals. The outcomes of this investigation showed that the abdominal surgery mostly affected the absorption process on the preenterocyte level, as indicated by the 2-fold increase in the extent of intestinal absorption of dexanabinol, which is a compound with a low degree of intestinal lymphatic transport. However, the lymphatic transport was not affected by the surgical procedure as evident by the absence of change in the extent of absorption of PRS-211,220, which is transported to the systemic circulation mainly by intestinal lymphatics. In conclusion, abdominal surgery can significantly affect the intestinal absorption of lipophilic drugs; however, intestinal lymphatic transport seems to be less affected by the abdominal surgery.

  13. Novel slow- and fast-type drug release round-window microimplants for local drug application to the cochlea: an experimental study in guinea pigs.

    PubMed

    Arnold, Wolfgang; Senn, Pascal; Hennig, Michael; Michaelis, Christiane; Deingruber, Kerstin; Scheler, Renate; Steinhoff, Hans-Joachim; Riphagen, Frits; Lamm, Kerstin

    2005-01-01

    Novel drug release microimplants (0.8 x 1.14 mm; custom-made by Leiras, now Schering OY, Finland) of slow- and fast-release types containing either 0.9 mg beclomethasone or no drug at all were placed unilaterally onto the round-window membrane (RWM) of 45 guinea pigs for a maximum duration of 28 days. The following parameters were tested on days 1, 14 and 28 after implantation: threshold levels of beclomethasone in the perilymph of the scala tympani, auditory brain stem responses (ABR thresholds and ABR threshold shifts), RWM morphology and hair cell loss (cytocochleograms). None of the animals in the non-implanted control group (n = 5) or placebo implant group (n = 15), but all animals in the slow-release-type implant group (n = 15) and fast-release-type implant group (n = 15) revealed the presence of beclomethasone on day 1 (34.9 and 64.3 pg/microl, respectively), day 14 (43.8 and 46.9 pg/microl, respectively) and day 28 after implantation (4.7 and 60.5 pg/microl, respectively). Histology of the RWMs appeared normal, and cytocochleograms revealed no inner hair cell loss and outer hair cell loss within normal ranges (from 0.5 +/- 0.4 to 0.8 +/- 0.2% per cochlea) in both ears in all experimental groups at any time during examination (days 1, 14 and 28). Initial values of ABR thresholds at 3, 6, 9 and 12 kHz did not differ significantly in any of the experimental groups. In non-implanted controls, no significant differences of ABR thresholds were observed in all frequencies tested in either ear on days 1, 14 and 28 compared to initial values, and ABR threshold shifts ranged from -3 +/- 5 dB (min.) to +5 +/- 7 dB (max.). On day 28 after implantation, there were no significant differences of ABR threshold shifts between this and the implant groups, except for 6 kHz of the slow-release device. Therefore, the placebo implants, the slow-release and the fast-release beclomethasone implants appear suitable for further experiments.

  14. Distinguishing between the Permeability Relationships with Absorption and Metabolism To Improve BCS and BDDCS Predictions in Early Drug Discovery

    PubMed Central

    2015-01-01

    The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug–drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption. PMID:24628254

  15. Design considerations to minimize the impact of drug absorption in polymer-based organ-on-a-chip platforms.

    PubMed

    Shirure, V S; George, S C

    2017-02-14

    Biocompatible polymers, such as polydimethylsiloxane (PDMS), are the materials of choice for creating organ-on-a-chip microfluidic platforms. Desirable qualities include ease of fabrication, optical clarity, and hydrophobicity, the latter of which facilitates oxygen transport to encased cells. An emerging and important application of organ-on-a-chip technology is drug discovery; however, a potential issue for polymer-based microfluidic devices has been highlighted by recent studies with PDMS, which have demonstrated absorption (and thus loss) of hydrophobic drugs into PDMS under certain experimental conditions. Absorption of drug in the polymer can also lead to undesirable transfer of drug between adjacent microfluidic lines. Given the benefits of polymers, it is essential to develop a comprehensive understanding of drug absorption. In this study, we considered convection, dissolution, and diffusion of a drug within a polymer-based microfluidic device to characterize the dynamics of drug loss in a quantitative manner. We solved Fick's 2nd law of diffusion (unsteady diffusion-convection) by finite element analysis in COMSOL®, and experimentally validated the numerical model for loss of three hydrophobic molecules (rhodamine B, cyanine NHS ester, and paclitaxel) in PDMS. Drug loss, as well as the unintended mixing of drugs by adjacent microfluidic channels, depends strongly on platform design parameters, experimental conditions, and the physico-chemical properties of the drug, and can be captured in a simple quantitate relationship that employs four scalable dimensionless numbers. This simple quantitative framework can be used in the design of a wide range of polymer-based microfluidic devices to minimize the impact of drug absorption.

  16. Determination of some antihistaminic drugs by atomic absorption spectrometry and colorimetric methods.

    PubMed

    El-Kousy, N; Bebawy, L I

    1999-08-01

    Atomic absorption spectrometry (AAS) and colourimetric methods have been developed for the determination of pizotifen (I), ketotifen (II) and loratadine (III). The first method depends on the reaction of the three drugs (I); (II) and (III) with cobalt thiocyanate reagent at pH 2 to give ternary complexes. These complexes are readily extracted with organic solvent and estimated by indirect atomic absorption method via the determination of the cobalt content in the formed complex after extraction in 0.1 M hydrochloric acid. It was found that the three drugs can be determined in the concentration ranges from 10 to 74, 12 to 95 and 10 to 93 microg ml(-1) with mean percentage recovery of 99.71+/-0.87, 99.70+/-0.79 and 99.62+/-0.75%, respectively. The second method is based on the formation of orange red ion pairs as a result of the reaction between (I); (II) and (III) and molybdenum thiocyanate with maximum absorption at 469.5 nm in dichloromethane. Appropriate conditions were established for the colour reaction. Under the proposed conditions linearity was obeyed in the concentration ranges 3.5-25, 5-37.5 and 2.5-22.5 microg ml(-1) with mean percentage recovery of 99.60+/-0.41, 100.11+/-0.43 and 99.31+/-0.47% for (I): (II) and (III), respectively. The third method depends on the formation of radical ion using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). The colour formed was measured at 588 nm for the three drugs (I); (II) and (III), respectively. The method is valid in concentration range 10-80 microg ml(-1) with mean percentage recovery 99.75+/-0.44, 99.94+/-0.72 and 99.17+/-0.36% for (I); (II) and (III), respectively. The proposed methods were applied to the analysis of pharmaceutical preparations. The results obtained were statistically analysed and compared with those obtained by applying the official and reference methods.

  17. A drug-in-adhesive matrix based on thermoplastic elastomer: evaluation of percutaneous absorption, adhesion, and skin irritation.

    PubMed

    Wang, ChengXiao; Liu, Ran; Tang, XiuZhen; Han, Wei

    2012-12-01

    A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene-isoprene-styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.

  18. [Inhibitory effect of nasal mucus on the absorption of drugs through respiratory epithelium].

    PubMed

    Hayashi, H

    1990-01-01

    The absorption of Dibekacin (DKB) through rabbit's tracheal mucosa with and without nasal mucus were examined in vitro. The modified double chamber method was used for the purpose of this study. DKB solution (20 mg/ml) and Hanks' balanced salt solution were put into the donor compartment (DC) and the receiver compartment (RC), respectively. A plate with a hole and the tracheal mucosa were inserted between the compartments in the order of DC, dialytic membrane, the plate, the rabbit tracheal mucosa and RC. The hole of the plate was filled with nasal mucus or Hanks' solution. The latter was used as the control. The chamber was incubated in a humidified atmosphere of 5% CO2 in air for 3 hours at 37 degrees C. The absorption rate (AR) was obtained by dividing the concentration of DKB in RC by that in DC. The nasal mucus from patients with chronic sinusitis significantly decreased the AR of DKB compared with that in the control (P less than 0.05). The AR significantly decreased with increments in the thickness of nasal mucus by chronic sinusitis. This decreased AR was improved by the addition of N-Acetyl-L-cysteine (NAC) to DKB solution in DC. NAC can cleave disulfied bonds of mucus glycoprotein and this results in the decrease of viscoelasticity of nasal mucus. The results indicate that nasal mucus by chronic sinusitis intercept the absorption of drugs through respiratory epithelium in vitro. One of the mechanisms of the intercepter may be due to the high molecular-reticular structure of nasal mucus.

  19. Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo.

    PubMed

    Linn, Michael; Collnot, Eva-Maria; Djuric, Dejan; Hempel, Katja; Fabian, Eric; Kolter, Karl; Lehr, Claus-Michael

    2012-02-14

    As many new active pharmaceutical ingredients are poorly water soluble, solubility enhancers are one possibility to overcome the hurdles of drug dissolution and absorption in oral drug delivery. In the present work a novel solubility enhancing excipient (Soluplus®) was tested for its capability to improve intestinal drug absorption. BCS class II compounds danazol, fenofibrate and itraconazole were tested both in vivo in beagle dogs and in vitro in transport experiments across Caco-2 cell monolayers. Each drug was applied as pure crystalline substance, in a physical mixture with Soluplus®, and as solid solution of the drug in the excipient. In the animal studies a many fold increase in plasma AUC was observed for the solid solutions of drug in Soluplus® compared to the respective pure drug. An effect of Soluplus® in a physical mixture with the drug could be detected for fenofibrate. In vitro transport studies confirm the strong effect of Soluplus® on the absorption behavior of the three tested drugs. Furthermore, the increase of drug flux across Caco-2 monolayer is correlating to the increase in plasma AUC and C(max)in vivo. For these poorly soluble substances Soluplus® has a strong potential to improve oral bioavailability. The applicability of Caco-2 monolayers as tool for predicting the in vivo transport behavior of the model drugs in combination with a solubility enhancing excipient was shown. Also the improvement of a solid dispersion compared to physical mixtures of the drugs and the excipient was correctly reflected by Caco-2 experiments. In the case of fenofibrate the possible improvement by a physical mixture was demonstrated, underscoring the value of the used tool as alternative to animal studies.

  20. Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug.

    PubMed

    Kossena, Greg A; Charman, William N; Boyd, Ben J; Porter, Christopher J H

    2005-03-01

    The influence of different model intestinal phases (modelled on those likely to be produced in vivo after the digestion of commonly used formulation lipids) on the absorption profile of cinnarizine has been studied. Combinations of C8, C12, or C18:1 fatty acid and monoglyceride and simulated endogenous intestinal fluid were formulated to provide examples of liquid (L1), lamellar (L(alpha)), and cubic (C) liquid crystalline phases. Phases containing cinnarizine were dosed intraduodenally and absorption was assessed in an anesthetized rat model. Bile duct ligation was performed to inhibit the effects of digestion/dilution on the phase structure. Absorption from the L(alpha) phases (C8 and C12 lipids) was statistically higher (p < 0.05) than a cinnarizine suspension: however, a statistically significant difference was not observed from the L1 and C phases. The rigid C18:1 C phase showed evidence of providing for sustained drug absorption. Experiments in bile intact rats with the C8 L(alpha) and C18:1 C phase highlighted that the absorption-modifying properties of these phases were influenced by dilution in the endogenous bile milieu, with absorption from L(alpha) phase reducing (possibly through precipitation of solubilized drug) and increasing in the case of the C18:1 C phase, possibly through the coexistence of L1 and C upon dilution permitting more efficient transfer of solubilized drug.

  1. Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption.

    PubMed

    Jakubiak, Paulina; Wagner, Björn; Grimm, Hans Peter; Petrig-Schaffland, Jeannine; Schuler, Franz; Alvarez-Sánchez, Rubén

    2016-02-01

    Drug absorption is a complex process involving dissolution and precipitation, along with other kinetic processes. The purpose of this work was to (1) establish an in vitro methodology to study dissolution and precipitation in early stages of drug development where low compound consumption and high throughput are necessary, (2) develop a mathematical model for a mechanistic explanation of generated in vitro dissolution and precipitation data, and (3) extrapolate in vitro data to in vivo situations using physiologically based models to predict oral drug absorption. Small-scale pH-shift studies were performed in biorelevant media to monitor the precipitation of a set of poorly soluble weak bases. After developing a dissolution-precipitation model from this data, it was integrated into a simplified, physiologically based absorption model to predict clinical pharmacokinetic profiles. The model helped explain the consequences of supersaturation behavior of compounds. The predicted human pharmacokinetic profiles closely aligned with the observed clinical data. In summary, we describe a novel approach combining experimental dissolution/precipitation methodology with a mechanistic model for the prediction of human drug absorption kinetics. The approach unifies the dissolution and precipitation theories and enables accurate predictions of in vivo oral absorption by means of physiologically based modeling.

  2. CAVE WINDOW

    DOEpatents

    Levenson, M.

    1960-10-25

    A cave window is described. It is constructed of thick glass panes arranged so that interior panes have smaller windowpane areas and exterior panes have larger areas. Exterior panes on the radiation exposure side are remotely replaceable when darkened excessively. Metal shutters minimize exposure time to extend window life.

  3. In vitro-in vivo correlation of the effect of supersaturation on the intestinal absorption of BCS Class 2 drugs.

    PubMed

    Higashino, Haruki; Hasegawa, Tsubasa; Yamamoto, Mari; Matsui, Rie; Masaoka, Yoshie; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji

    2014-03-03

    The aim of this study was to establish an in vitro method for evaluating the effect of supersaturation on oral absorption of poorly water-soluble drugs in vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model drugs. Supersaturation of each drug was induced by diluting its stock solution by fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then dissolution and precipitation profile of the drug was observed in vitro. The crystalline form of the precipitate was checked by differential scanning calorimetry (DSC). For comparison, control suspension was prepared by suspending a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal absorption of the drug was observed in rats by determined the plasma concentration after intraduodenal administration of drug suspensions. For all drugs, suspensions prepared by solvent-shift method showed significantly higher dissolved concentration in vitro than that prepared by powder-suspending method, clearly indicated the induction of supersaturation. DSC analysis revealed that crystalline form of the precipitate profoundly affects the extent and the duration of supersaturation. A rat in vivo study confirmed that the supersaturation of these drugs increased the fraction absorbed from the intestine, which corresponded well to the in vitro dissolution and precipitation profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption study was performed in rats pretreated with 1-aminobenzotriazole, a potent inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the high luminal concentration of ketoconazole caused by supersaturation saturated the metabolic enzymes and further increased the systemic exposure of the absorbed drug. The additional effects of supersaturation on the absorption of ketoconazole are consistent with previous studies in humans under differing gastric pH conditions. In conclusion, effects of supersaturation on

  4. Effect on the Gastrointestinal Absorption of Drugs from Different Classes in the Biopharmaceutics Classification System, When Treating with Liraglutide.

    PubMed

    Malm-Erjefält, Monika; Ekblom, Marianne; Vouis, Jan; Zdravkovic, Milan; Lennernäs, Hans

    2015-11-02

    Like other GLP-1 receptor agonists used for treatment of type 2 diabetes, liraglutide delays gastric emptying. In this clinical absorption study, the primary objective was to investigate the effect of liraglutide (at steady state) on the rate and/or extent of gastrointestinal (GI) absorption of concomitantly orally taken drugs from three classes of the Biopharmaceutics Classification System (BCS). To provide a general prediction on liraglutide drug-drug absorption interaction, single-dose pharmacokinetics of drugs representing BCS classes II (low solubility-high permeability; atorvastatin 40 mg and griseofulvin 500 mg), III (high solubility-low permeability; lisinopril 20 mg), and IV (low solubility-low permeability; digoxin 1 mg) were studied in healthy subjects at steady state of liraglutide 1.8 mg, or placebo, in a two-period crossover design. With liraglutide, the oral drugs atorvastatin, lisinopril, and digoxin showed delayed tmax (by ≤2 h) and did not meet the criterion for bioequivalence for Cmax (reduced Cmax by 27-38%); griseofulvin had similar tmax and 37% increased Cmax. Although the prespecified bioequivalence criterion was not met by all drugs, the overall plasma exposure (AUC) of griseofulvin, atorvastatin, lisinopril, and digoxin only exhibited minor changes and was not considered to be of clinical relevance.

  5. Window generator

    NASA Astrophysics Data System (ADS)

    Johnson, William K.; May, Roger A.

    1989-03-01

    The present invention relates generally to video target recognition systems and more specifically to a window generator which receives a field of video data and applies an identification code to rectangular subregions to identify distinct target areas within a given background area. The present invention comprises a window generator which provides a 6 bit target identification number for up to 63 target areas and one background area in a frame of serially scanned data. The window generator receives a field of video data from an image data source. This video data consists of digitized frames of serially scanned data similar to a conventional television screen image, which is divided horizontally in pixels, and vertically in lines. The window generator permits any given frame to be subdivided into specific rectangular subregions, which may be located anywhere on the video picture. By allowing statistics to be collected on the individual subregions (or target areas) the window generator permits local processing of video data within the specified target areas as opposed to processing of video data over the entire video field. One embodiment of the window generator is composed of: a microprocessor, a random access memory (RAM), a comparator, a line memory, two counters, an OR gate, a frame initialization circuit, and a buffer. These elements function as described below.

  6. [Inhaled treatments: Choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract].

    PubMed

    Benattia, A; Cavaillon, P; Gachelin, E; Devillier, P; Vecellio, L; Williams, G; Dubus, J-C

    2015-10-01

    Inhaled drugs are now routinely prescribed in daily medical practice. Recent topics about these treatments have been developed during the fourth annual meeting of the Groupe de travail aérosolthérapie (GAT) of the French-speaking respiratory society (Société de pneumologie de langue française). This article focuses mainly upon the choice of devices, systemic absorption of inhaled drugs and bitter taste receptors in the respiratory tract, a potential new target for drug development.

  7. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

    PubMed Central

    Zhang, Xingwang; Chen, Guijiang; Zhang, Tianpeng; Ma, Zhiguo; Wu, Baojian

    2014-01-01

    Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN), a Biopharmaceutics Classification System (BCS) II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs) were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®), respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs. PMID:25473287

  8. In vitro skin absorption and drug release - a comparison of six commercial prednicarbate preparations for topical use.

    PubMed

    Lombardi Borgia, S; Schlupp, P; Mehnert, W; Schäfer-Korting, M

    2008-02-01

    Reconstructed human epidermis is a useful tool for in vitro skin absorption studies of chemical compounds. If this may hold true also for topical dermatics, we investigated the glucocorticoid prednicarbate applied by two sets (innovator and generic) of cream, ointment and fatty ointment using the commercially available EpiDerm model. Moreover, stability and local tolerability of the preparations as well as drug release were studied, to estimate an influence on prednicarbate absorption and metabolism. While release ranked in the order creamdrugs subject to skin metabolism, cutaneous uptake is not to be derived from drug release studies, yet has to be studied experimentally with viable skin or reconstructed human epidermis.

  9. Gastroretentive inorganic-organic hybrids to improve class IV drug absorption.

    PubMed

    Perioli, Luana; Pagano, Cinzia

    2014-12-30

    Therapeutic efficacy of some orally administered molecules is often conditioned by their solubility in physiological fluids as well as their absorption. The last aspect becomes more limitative and conditioning drug plasmatic profiles when the active ingredient is preferentially absorbed in a specific region of the gastrointestinal tract. A case is represented by furosemide (FURO) preferentially absorbed in the stomach, site in which, because of its acidic nature, is poorly soluble. To solve this problem new oral solid formulations have been developed. The inorganic-organic hybrid MgAl-HTlc-FURO has been formulated in tablet in which floating and mucoadhesion properties have been combined. Swellable (Methocel K4, Methocel K15, Methocel K100 M, hydroxypropyl methyl cellulose) or swellable/erodible polymers (Methocel E50 LV, Methocel K100 LV), used to obtain the floating, were combined to Carbopol(®) (971P or 974P) to confer mucoadhesion capacity. Prepared tablets were deeply characterized in terms of hydration capacity, erosion %, buoyancy lag time/floating time and mucoadhesion. The most suitable tablets selected from these preliminary tests, submitted to in vitro release studies, showed a sustained release of FURO. This is useful to maintain the therapeutic concentrations for a long time, in comparison to conventional dosage forms, thanking to the enhancement of formulation residence time in the stomach.

  10. Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate.

    PubMed

    Kesisoglou, Filippos; Xia, Binfeng; Agrawal, Nancy G B

    2015-11-01

    In vitro-in vivo correlations (IVIVC) are predictive mathematical models describing the relationship between dissolution and plasma concentration for a given drug compound. The traditional deconvolution/convolution-based approach is the most common methodology to establish a level A IVIVC that provides point to point relationship between the in vitro dissolution and the in vivo input rate. The increasing application of absorption physiologically based pharmacokinetic model (PBPK) has provided an alternative IVIVC approach. The current work established and compared two IVIVC models, via the traditional deconvolution/convolution method and via absorption PBPK modeling, for two types of modified release (MR) formulations (matrix and multi-particulate tablets) of MK-0941, a BCS III drug development candidate. Three batches with distinct release rates were studied for each formulation technology. A two-stage linear regression model was used for the deconvolution/convolution approach while optimization of the absorption scaling factors (a model parameter that relates permeability and input rate) in Gastroplus(TM) Advanced Compartmental Absorption and Transit model was used for the absorption PBPK approach. For both types of IVIVC models established, and for either the matrix or the multiparticulate formulations, the average absolute prediction errors for AUC and C max were below 10% and 15%, respectively. Both the traditional deconvolution/convolution-based and the absorption/PBPK-based level A IVIVC model adequately described the compound pharmacokinetics to guide future formulation development. This case study highlights the potential utility of absorption PBPK model to complement the traditional IVIVC approaches for MR products.

  11. The role of clinical pharmacists in educating nurses to reduce drug-food interactions (absorption phase) in hospitalized patients.

    PubMed

    Abbasi Nazari, Mohammad; Salamzadeh, Jamshid; Hajebi, Giti; Gilbert, Benjamin

    2011-01-01

    Drug-food interactions can increase or decrease drug effects, resulting in therapeutic failure or toxicity. Activities that reduce these interactions play an important role for clinical pharmacists. This study was planned and performed in order to determine the role of clinical pharmacist in the prevention of absorption drug-food interactions through educating the nurses in a teaching hospital affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran. The rate of interactions was determined using direct observation methods before and after the nurse training courses in four wards including gastrointestinal-liver, endocrine, vascular surgery and nephrology. Training courses consisted of the nurse attendance lecture delivered by a clinical pharmacist which included receiving information pamphlets. Total incorrect drug administration fell down from 44.6% to 31.5%. The analysis showed that the rate of absorption drug-food interactions significantly decreased after the nurse training courses (p < 0.001). Clinical pharmacist can play an important role in nurse training as an effective method to reduce drug-food interactions in hospitals.

  12. Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption.

    PubMed

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Al-Suwayeh, Saleh A; Li, Yi-Ching; Fang, Jia-You

    2012-06-01

    While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 μm, 2.5 J/cm²) to approach the epidermis (25 μm, 6.25 J/cm²) and upper dermis (40 μm, 10 J/cm²). Reepithelialization evaluated by transepidermal water loss was complete within 2-4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4-6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109-188 ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2-3-fold. The experimental results indicated that clinicians should be cautious when determining the

  13. Rapid screening and identification of illicit drugs by IR absorption spectroscopy and gas chromatography

    NASA Astrophysics Data System (ADS)

    Mengali, Sandro; Liberatore, Nicola; Luciani, Domenico; Viola, Roberto; Cardinali, Gian Carlo; Elmi, Ivan; Poggi, Antonella; Zampolli, Stefano; Biavardi, Elisa; Dalcanale, Enrico; Bonadio, Federica; Delemont, Olivier; Esseiva, Pierre; Romolo, Francesco S.

    2013-01-01

    Analytical instruments based on InfraRed Absorption Spectroscopy (IRAS) and Gas Chromatography (GC) are today available only as bench-top instrumentation for forensic labs and bulk analysis. Within the 'DIRAC' project funded by the European Commission, we are developing an advanced portable sensor, that combines miniaturized GC as its key chemical separation tool, and IRAS in a Hollow Fiber (HF) as its key analytical tool, to detect and recognize illicit drugs and key precursors, as bulk and as traces. The HF-IRAS module essentially consists of a broadly tunable External Cavity (EC) Quantum Cascade Laser (QCL), thermo-electrically cooled MCT detectors, and an infrared hollow fiber at controlled temperature. The hollow fiber works as a miniaturized gas cell, that can be connected to the output of the GC column with minimal dead volumes. Indeed, the module has been coupled to GC columns of different internal diameter and stationary phase, and with a Vapour Phase Pre-concentrator (VPC) that selectively traps target chemicals from the air. The presentation will report the results of tests made with amphetamines and precursors, as pure substances, mixtures, and solutions. It will show that the sensor is capable of analyzing all the chemicals of interest, with limits of detection ranging from a few nanograms to about 100-200 ng. Furthermore, it is suitable to deal with vapours directly trapped from the headspace of a vessel, and with salts treated in a basic solution. When coupled to FAST GC columns, the module can analyze multi-components mixes in less than 5 minutes.

  14. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms.

    PubMed

    Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro; Kato, Takashi; Kushida, Ikuo

    2012-01-01

    In order to better understand the oral absorption behavior of poorly water-soluble drugs, their supersaturation-nucleation behavior was characterized in fasted state simulated intestinal fluid. The induction time (t(ind)) for nucleation was measured for four model drugs: itraconazole, erlotinib, troglitazone, and PLX4032. Supersaturated solutions were prepared by solvent shift method, and nucleation initiation was monitored by ultraviolet detection. The relationship between t(ind) and degree of supersaturation was analyzed in terms of classical nucleation theory. The defined supersaturation stability proved to be compound specific. Clinical data on oral absorption were investigated for drugs in thermodynamically high-energy forms such as amorphous forms and salts and was compared with in vitro supersaturation-nucleation characteristics. Solubility-limited maximum absorbable dose was proportionate to intestinal effective drug concentrations, which are related to supersaturation stability and thermodynamic solubility. Supersaturation stability was shown to be an important factor in determining the effect of high-energy forms. The characterization of supersaturation-nucleation behavior by the presented method is, therefore, valuable for assessing the potential absorbability of poorly water-soluble drugs.

  15. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat.

    PubMed

    Lehr, C M; Bouwstra, J A; Kok, W; De Boer, A G; Tukker, J J; Verhoef, J C; Breimer, D D; Junginger, H E

    1992-05-01

    The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.

  16. Water-vapor foreign-continuum absorption in the 8-12 and 3-5 μm atmospheric windows

    NASA Astrophysics Data System (ADS)

    Klimeshina, T. E.; Rodimova, O. B.

    2015-08-01

    The frequency and temperature dependence of the water vapor-nitrogen continuum in the 8-12 and 3-5 μm spectral regions obtained experimentally by CAVIAR and NIST is described with the use of the line contour constructed on the basis of asymptotic line shape theory. The parameters of the theory found from fitting the calculated values of the absorption coefficient to the pertinent experimental data enter into the expression for the classical potential describing the center-of-mass motion of interacting molecules and into the expression for the quantum potential of two interacting molecules. The frequency behavior of the line wing contours appears to depend on the band the lines of which make a major contribution to the absorption in a given spectral interval. The absorption coefficients in the wings of the band in question calculated with the line contours obtained for other bands are outside of experimental errors. The distinction in the line wing behavior may be explained by the difference in the quantum energies of molecules interacting in different vibrational states.

  17. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

    PubMed

    Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2014-11-15

    The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery.

  18. Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

    PubMed

    Cai, Zheng; Huang, Juan; Luo, Hui; Lei, Xiaolu; Yang, Zhaoxiang; Mai, Yang; Liu, Zhongqiu

    2013-07-01

    Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.

  19. Profiling and trend analysis of food effects on oral drug absorption considering micelle interaction and solubilization by bile micelles.

    PubMed

    Kawai, Yukinori; Fujii, Yoshimine; Tabata, Fumiko; Ito, Junko; Metsugi, Yukiko; Kameda, Atsuko; Akimoto, Katsuya; Takahashi, Masayuki

    2011-01-01

    Correlation analysis between food effects on oral drug absorption (food effect) and physicochemical properties is important for efficient drug discovery and contributes to drug design. This study focused on micelle binding and solubilization considering bile micelles in the intestinal fluid. Profiling using about 40 launched drugs demonstrated that those in a high solubilization area (area 1) tended to have a positive food effect, and that drugs exhibiting negative/no food effect tended to coexist in a no/low solubilization area (area 2). In area 1, the solubilization effect by bile micelles was demonstrated quantitatively as an important factor that indicates a positive food effect. In area 2, the relative and quantitative relationships among the membrane permeation rate, dissolution rate, micelle binding and food effect could be clarified by simulation. The improvement of membrane permeability and the suppression of micelle binding are considered to be required to avoid a negative food effect. In conclusion, important factors contributing to the food effect were clarified relatively and quantitatively. Data generated from this profiling may be beneficial to find a solution for negative food effects. Furthermore, this risk assessment of food effects is considered to be a useful tool in rational drug design for drug discovery.

  20. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox).

    PubMed

    Szakács, Gergely; Váradi, András; Ozvegy-Laczka, Csilla; Sarkadi, Balázs

    2008-05-01

    ATP binding cassette (ABC) drug transporters play an important role in cancer drug resistance, protection against xenobiotics, and in general in the passage of drugs through cellular and tissue barriers. This review explores how human ABC transporters modulate the pharmacological effects of various drugs, and how this predictable ADME-TOX modulation can be used during the process of drug discovery and development. We provide a description of the relevant human ABC drug transporters and review the models and assay systems that can be applied for the analysis of their expected drug interactions. The use of the in vitro, in vivo, in silico models, their combination, and the emerging clinical information are evaluated with respect to their potential application in early drug screening.

  1. A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

    PubMed Central

    Remko, Milan; Remková, Anna; Broer, Ria

    2016-01-01

    Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values). The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Å2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA) values, exhibit the largest absorption. A high value of polar surface area (PSA) of cangrelor (255 Å2) results in substantial worsening of the absorption in comparison with thienopyridine drugs. PMID:27007371

  2. BERKELEY LAB WINDOW

    SciTech Connect

    Curcija, Dragan Charlie; Zhu, Ling; Czarnecki, Stephen; Mitchell, Robin D.; Kohler, Christian; Vidanovic, Simon V.; Huizenga, Charlie

    2015-03-06

    WINDOW features include: - Microsoft Windows TM interface - algorithms for the calculation of total fenestration product U-values and Solar Heat Gain Coefficient consistent with ASHRAE SPC 142, ISO 15099, and the National Fenestration Rating Council - a Condensation Resistance Index in accordance with the NFRC 500 Standard - and integrated database of properties - imports data from other LBNL window analysis software: - Import THERM file into the Frame Library - Import records from IGDB and OPtics5 into the Glass Library for the optical properties of coated and uncoated glazings, laminates, and applied films. Program Capabilities WINDOW 7.2 offers the following features: The ability to analyze products made from any combination of glazing layers, gas layers, frames, spacers, and dividers under any environmental conditions and at any tilt; The ability to model complex glazing systems such as venetian blinds and roller shades. Directly accessible libraries of window system components, (glazing systems, glazing layers, gas fills, frame and divider elements), and environmental conditions; The choice of working in English (IP), or Systeme International (SI) units; The ability to specify the dimensions and thermal properties of each frame element (header, sills, jamb, mullion) in a window; A multi-band (wavelength-by-wavelength) spectral model; A Glass Library which can access spectral data files for many common glazing materials from the Optics5database; A night-sky radiative model; A link with the DOE-2.1E and Energy Plus building energy analysis program. Performance Indices and Other Results For a user-defined fenestration system and user-defined environmental conditions, WINDOW calculates: The U-value, solar heat gain coefficient, shading coefficient, and visible transmittance for the complete window system; The U-value, solar heat gain coefficient, shading coefficient, and visible transmittance for the glazing system (center-of-glass values); The U-values of the

  3. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS).

    PubMed

    Lee, Dong Hoon; Yeom, Dong Woo; Song, Ye Seul; Cho, Ha Ra; Choi, Yong Seok; Kang, Myung Joo; Choi, Young Wook

    2015-01-15

    A novel supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to improve the oral absorption of dutasteride (DTS), a 5α-reductase inhibitor that is poorly water-soluble. A supersaturable system was prepared by employing Soluplus(®) (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) as a precipitation inhibitor with a conventional SEDDS vehicle consisted of Capryol™ 90, Cremophor(®) EL and Transcutol(®) HP (DTS:SEDDS vehicle:Soluplus(®)=1.0:67.6:10.0 w/v/w). In an in vitro dissolution test in a non-sink condition, the drug dissolution rate from SEDDS was rapidly increased to 72% for an initial period of 5min, but underwent rapid drug precipitation within 2h, decreasing the amount of drug dissolved to one-seventh of its original amount. On the other hand, S-SEDDS resulted in a slower crystallization of DTS by virtue of a precipitation inhibitor, maintaining a 3 times greater dissolution rate after 2h compared to SEDDS. In an in vivo pharmacokinetic study in rats, the S-SEDDS formulation exhibited 3.9-fold greater area-under-curve value than that of the drug suspension and 1.3-fold greater than that of SEDDS. The maximum plasma concentration of S-SEDDS was 5.6- and 2.0-fold higher compared to drug suspension and SEDDS, respectively. The results of this study suggest that the novel supersaturable system may be a promising tool for improving the physicochemical property and oral absorption of the 5α-reductase inhibitor.

  4. Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies.

    PubMed

    Kesisoglou, Filippos; Chung, John; van Asperen, Judith; Heimbach, Tycho

    2016-09-01

    In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in-human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post-FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions.

  5. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo.

    PubMed Central

    Nøhr, Martha Kampp; Thale, Zia I; Brodin, Birger; Hansen, Steen H; Holm, René; Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin in Caco-2 cells. Oral coadministration of vigabatrin and infant formula significantly reduced Cmax and prolonged tmax of vigabatrin absorption. Ligands for the proton-coupled amino acid transporter PAT1, sarcosine, and proline/l-tryptophan had similar effects on the pharmacokinetic profile of vigabatrin. The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems reasonable that infant formula may also directly affect the intestinal absorption rate of vigabatrin possibly via PAT1. PMID:25505585

  6. Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

    PubMed

    Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji

    2016-04-01

    The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of

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

    PubMed Central

    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

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

    PubMed

    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.

  9. Site-specific drug delivery to the middle-to-lower region of the small intestine reduces food-drug interactions that are responsible for low drug absorption in the fed state.

    PubMed

    Tanno, Fumié K; Sakuma, Shinji; Masaoka, Yoshie; Kataoka, Makoto; Kozaki, Toshio; Kamaguchi, Ryosei; Ikeda, Yutaka; Kokubo, Hiroyasu; Yamashita, Shinji

    2008-12-01

    Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effects). We designed enteric-coated tablets that start to disintegrate when they reach the middle-to-lower region of the small intestine, and examined whether they could reduce negative food effects in dogs. Tablets containing trientine as a model drug were coated with hypromellose acetate succinate (HPMCAS) with various values of succinoyl group content. The time lag of drug dissolution from these enteric-coated tablets in simulated intestinal fluid of pH 6.8 increased as the succinoyl group content was decreased. The AUC of trientine after oral administration of its aqueous solution to fed dogs was one-eighth of that in fasted dogs. The low drug absorption in fed dogs was improved when trientine was administered as enteric-coated tablets. The average ratio of AUC in the fed state to that in the fasted state increased with decreasing succinoyl group content of HPMCAS. Negative food effects completely disappeared after oral administration of tablets coated with HPMCAS having a succinoyl group content of 6.2% or less, which probably disintegrated in the middle-to-lower small intestine. Our results indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.

  10. A heuristic model to quantify the impact of excess cyclodextrin on oral drug absorption from aqueous solution.

    PubMed

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2016-05-01

    The intestinal drug solubilising capacity (Dtot(SC)) of a drug formulated as an aqueous cyclodextrin solution is a recently proposed quantity to predict the cyclodextrin concentration needed to fully solubilise the drug in the intestinal lumen. According to this concept, the cyclodextrin concentration in the drug product must be higher than the amount needed to solubilise the compound, due to the displacement of the drug from the cyclodextrin cavity by bile salts in the intestinal lumen. On the other hand, dosing cyclodextrin at >Dtot(SC) is expected to result in decreased free intestinal drug concentrations and thus potentially a lower fraction absorbed. In this study, data from three previous in vivo studies in rats with fixed concentrations of three compounds (danazol, cinnarizine and benzo[A]pyrene) and various cyclodextrin concentrations >Dtot(SC) were analysed. The model was developed for danazol and applied to the two other compounds. Absorption, as quantified from the area under the plasma concentration-time profile, was predicted by the model to decrease at elevated concentrations of co-administered cyclodextrin in accordance with the in vivo data. In addition, at high cyclodextrin concentrations a delay in Tmax and a decrease in Cmax were predicted, again in accordance with the experimental observations. These observations were rationalised in terms of the free intestinal drug concentration by a chemical equilibrium model for Dtot(SC). This model depends on the quantity termed the dimensionless dose concentration, Dtot(∗)=Do/Pn, given as the fraction of the permeation number (Pn) and dose number (Do). The model provides the formulation scientist with a critical quality attribute for assessing the implication of having excess cyclodextrin in an oral solution.

  11. Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper.

    PubMed

    Kraynov, Eugenia; Kamath, Amrita V; Walles, Markus; Tarcsa, Edit; Deslandes, Antoine; Iyer, Ramaswamy A; Datta-Mannan, Amita; Sriraman, Priya; Bairlein, Michaela; Yang, Johnny J; Barfield, Matthew; Xiao, Guangqing; Escandon, Enrique; Wang, Weirong; Rock, Dan A; Chemuturi, Nagendra V; Moore, David J

    2016-05-01

    An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs.

  12. Windows of detection of tetrazepam in urine, oral fluid, beard, and hair, with a special focus on drug-facilitated crimes.

    PubMed

    Concheiro, Marta; Villain, Marion; Bouchet, Stéphane; Ludes, Bertrand; López-Rivadulla, Manuel; Kintz, Pascal

    2005-10-01

    Reducing the capacity of a victim to react against sexual assault, coupled with a possible abrupt unconsciousness-inducing effect and ease of administration in spiked drinks, have resulted in the use of sedative agents in cases of drug-facilitated offence. Among these compounds, tetrazepam may impair an individual rapidly. The chances of detecting this substance increase if the most sensitive methods are used and if the biologic matrix that allows the longest possible detection time is available. To document the window of detection of tetrazepam, 50 mg of the drug was administered orally to 2 volunteers, and the following samples were collected: oral fluid (n = 1) over 515 minutes, urine (n = 2) over 236-240 hours, hair (n = 2) 4 weeks after exposure, and beard (n = 1) over 34 days. Tetrazepam was analyzed by LC-MS/MS (Micromass Quattro Micro) after alkalinization and extraction by dichloromethane/diethyl ether in the presence of diazepam-d5, used as internal standard. Reversed-phase separation on an XTerra MS C18 column was achieved in 12 minutes, under gradient conditions. Pseudo-molecular ions selected were m/z 289.2 and 290.2 for tetrazepam and the internal standard (IS), respectively, and the corresponding daughter ions selected were m/z 225.2 and 253.2 for tetrazepam and m/z 154.1 and 198.3 for the IS. Urine tested positive for tetrazepam over 236-240 hours (14-13 ng/mL). Oral fluid tested positive for tetrazepam over 515 minutes (2.5 ng/mL). Tetrazepam was detected in beard over 27 days (6.5 pg/mg). A single tetrazepam dose was detected in hair 4 weeks after intake (123-175 pg/mg). Tetrazepam tested positive over the studied time intervals but would be expected to be detectable for a considerably longer time. Therefore, in cases of drug-facilitated crimes in which tetrazepam is involved, hair and beard analyses can be an important complement to urine analyses to document exposure, particularly if LC-MS/MS is used.

  13. Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

    NASA Astrophysics Data System (ADS)

    Syed, Mohammed Irfan

    was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

  14. Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs.

    PubMed

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup; Andersson, Sara B E; Artursson, Per; Beato, Stefania; Borde, Anders; Box, Karl; Brewster, Marcus; Dressman, Jennifer; Feng, Kung-I; Halbert, Gavin; Kostewicz, Edmund; McAllister, Mark; Muenster, Uwe; Thinnes, Julian; Taylor, Robert; Mullertz, Anette

    2014-06-16

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered.

  15. Colorimetric and atomic absorption spectrometric determination of mucolytic drug ambroxol through ion-pair formation with iron and thiocyanate.

    PubMed

    Levent, Abdulkadir; Sentürk, Zühre

    2010-09-01

    Colorimetric and atomic absorption spectrometric methods have been developed for the determination of mucolytic drug Ambroxol. These procedures depend upon the reaction of iron(III) metal ion with the drug in the presence of thiocyanate ion to form stable ion-pair complex which extractable chloroform. The red-coloured complex was determined either colorimetrically at 510 nm or by indirect atomic absorption spectrometry (AAS) via the determination of the iron content in the formed complex. The optimum experimental conditions for pH, concentrations of Fe(3+) and SCN(-), shaking time, phase ratio, and the number of extractions were determined. Under the proposed conditions, linearity was obeyed in the concentration ranges 4.1x10(-6) - 5.7x10(-5) M (1.7-23.6 µg mL(-1)) using both methods, with detection limits of 4.6x10(-7) M (0.19 µg mL(-1)) for colorimetry and 1.1x10(-6) M (0.46 µg mL(-1)) for AAS. The proposed methods were applied for the determination of Ambroxol in tablet dosage forms. The results obtained were statistically analyzed and compared with those obtained by applying the high-performance liquid chromatographic method with diode-array detection.

  16. Oral delivery system for two-pulse colonic release of protein drugs and protease inhibitor/absorption enhancer compounds.

    PubMed

    Del Curto, Maria Dorly; Maroni, Alessandra; Palugan, Luca; Zema, Lucia; Gazzaniga, Andrea; Sangalli, Maria Edvige

    2011-08-01

    It is well known that the intestinal stability and absorption of protein drugs are improved when enzyme inhibitors/permeation enhancers are coadministered. Recently, it was hypothesized that an increased effectiveness of these adjuvants might be achieved by timing their release prior to that of the protein, so that a more favorable environment would be established in advance. Therefore, an oral system was proposed for two-pulse colonic release of insulin and the protease inhibitor camostat mesilate/absorption enhancer sodium glycocholate. The device consisted of a drug-containing core, an inner swellable/erodible low-viscosity hydroxypropyl methylcellulose (HPMC) coating, an intermediate adjuvant layer, and an additional outer HPMC coating. HPMC coats and camostat mesilate/sodium glycocholate films with differing thicknesses were applied to immediate-release tablet cores by aqueous spray coating. The obtained units were characterized for weight, thickness, breaking force, and release performance. All systems showed satisfactory technological properties and the pursued pulsatile delivery behavior, with programmable delay phases preceding inhibitor/enhancer release and elapsing between inhibitor/enhancer and protein release, respectively. Indeed, both lag times linearly correlated with the relevant HPMC coating level. The system was thus proven suitable for yielding two-pulse release profiles, in which lag phases could be modulated to provide convenient concentration patterns for proteins and adjuvants.

  17. Assessment of In Vivo Clinical Product Performance of a Weak Basic Drug by Integration of In Vitro Dissolution Tests and Physiologically Based Absorption Modeling.

    PubMed

    Ding, Xuan; Gueorguieva, Ivelina; Wesley, James A; Burns, Lee J; Coutant, Carrie A

    2015-11-01

    Effective integration of in vitro tests and absorption modeling can greatly improve our capability in understanding, comparing, and predicting in vivo performances of clinical drug products. In this case, we used a proprietary drug candidate galunisertib to describe the procedures of designing key in vitro tests, analyzing relevant experimental and trial data, and integrating them into physiologically based absorption models to evaluate the performances of its clinical products. By simulating the preclinical study result, we estimated high in vivo permeability for the drug. Given the high sensitivity of its solubility to pH, supersaturation may play an important role in the absorption of galunisertib. Using the dynamic dissolution test, i.e., artificial stomach-duodenum (ASD) model and simulation, we concluded galunisertib in solution or tablet products could maintain supersaturation during the transit in the gastrointestinal tract (GIT). A physiologically based absorption model was established by incorporating these key inputs in the simulation of Trial 1 results of galunisertib solution. To predict the performance of three tablet products, we developed z-factor dissolution models from the multi-pH USP dissolution results and integrate them into the absorption model. The resultant biopharmaceutical models provided good prediction of the extent of absorption of all three products, but underestimated the rate of absorption of one tablet product. Leveraging the ASD result and optimization with the dissolution model, we identified the limitation of the model due to complexity of estimating the dissolution parameter z and its in vitro-in vivo correlation.

  18. A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption.

    PubMed

    Augustijns, Patrick; Wuyts, Benjamin; Hens, Bart; Annaert, Pieter; Butler, James; Brouwers, Joachim

    2014-06-16

    The purpose of this paper is to collate all recently published solubility data of orally administered drugs in human intestinal fluids (HIF) that were aspirated from the upper small intestine (duodenum and jejunum). The data set comprises in total 102 solubility values in fasted state HIF and 37 solubility values in fed state HIF, covering 59 different drugs. Despite differences in the protocol for HIF sampling and subsequent handling, this summary of HIF solubilities provides a critical reference data set to judge the value of simulated media for intestinal solubility estimation. In this regard, the review includes correlations between the reported solubilizing capacity of HIF and fasted or fed state simulated intestinal fluid (FaSSIF/FeSSIF). Correlating with HIF solubilities enables the optimal use of solubility measurements in simulated biorelevant media to obtain accurate estimates of intestinal solubility during drug development. Considering the fraction of poorly soluble new molecular entities in contemporary drug discovery, adequate prediction of intestinal solubility is critical for efficient lead optimization, early candidate profiling, and further development.

  19. Reply to "On the Effect of Common Excipients on the Oral Absorption of Class 3 Drugs".

    PubMed

    Vaithianathan, Soundarya; Haidar, Sam H; Zhang, Xinyuan; Jiang, Wenlei; Avon, Christopher; Dowling, Thomas C; Shao, Changxing; Kane, Maureen; Hoag, Stephen W; Flasar, Mark H; Ting, Tricia Y; Polli, James E

    2016-04-01

    We previously concluded that 12 common excipients need not be qualitatively the same and quantitatively very similar to reference for Biopharmaceutics Classification System-based biowaivers. This conclusion for regulatory relief is based upon a series of bioequivalence studies in humans involving cimetidine and acyclovir. Limitations were also discussed. We understand the major concern of García-Arieta et al. is that "results obtained by Vaithianathan et al. should not be extrapolated to other drugs." We understand that individuals conducting their own risk/benefit analysis may reach that conclusion, and we reply to the concerns of García-Arieta et al. We continue to conclude that the 12 common excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather, simply be not more than the quantities studied in our manuscript for cimetidine and acyclovir, and potentially other class 3 drugs with similar properties.

  20. Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles

    PubMed Central

    Lv, Liang-Zhong; Tong, Chen-Qi; Yu, Jia; Han, Min; Gao, Jian-Qing

    2013-01-01

    Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability. This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA. Transmission electron microscopy and freeze-fracture replication transmission election microscopy showed that the HSYA nanoparticles have an irregular shape and a narrow size distribution. Zonula occludens 1 protein (ZO–1) labeling showed that the nanoparticles with different dilutions produced an opening in the tight junctions of Caco-2 cells without inducing cytotoxicity to the cells. Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo. PMID:23935363

  1. Non-Destructive and Discriminating Identification of Illegal Drugs by Transient Absorption Spectroscopy in the Visible and Near-IR Wavelength Range

    NASA Astrophysics Data System (ADS)

    Sato, Chie; Furube, Akihiro; Katoh, Ryuzi; Nonaka, Hidehiko; Inoue, Hiroyuki

    2008-11-01

    We have tested the possibility of identifying illegal drugs by means of nanosecond transient absorption spectroscopy with a 10-ns UV-laser pulse for the excitation light and visible-to-near-IR light for the probe light. We measured the transient absorption spectra of acetonitrile solutions of d-methamphetamine, dl-3,4-methylenedioxymethamphetamine hydrochloride (MDMA), and dl-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine hydrochloride (MBDB), which are illegal drugs widely consumed in Japan. Transient absorption signals of these drugs were observed between 400 and 950 nm, a range in which they are transparent in the ground state. By analyzing the spectra in terms of exponential and Gaussian functions, we could identify the drugs and discriminate them from chemical substances having similar structures. We propose that transient absorption spectroscopy will be a useful, non-destructive method of inspecting for illegal drugs, especially when they are dissolved in liquids. Such a method may even be used for drugs packed in opaque materials if it is further extended to utilize intense femtosecond laser pulses.

  2. The 'Formaldehyde Window'

    NASA Astrophysics Data System (ADS)

    Lawton, A. T.

    1981-09-01

    The characteristics obtained by using the absorption line of formaldehyde as a background for a transmitted signal are examined and compared with the Water Hole concept. It is shown that much greater distance may be accessed for a given transmitter power level and that the narrow band characteristics of the formaldehyde line are ideally suited to the transmission of low frequency coded 'calling' signals. It is further shown that two unique harmonic overtones lie above and below the 4830 MHz formaldehyde line, and by using these further aids, a clear and unambiguous interstellar communication system could be established without the background maser noise that would be expected from the use of the Water Hole. It is concluded that the Formaldehyde Window is a viable alternative to the Water Hole concept, with an advantage of being an easily distinguished artifact of intelligence.

  3. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.

    PubMed

    Miyata, Masaaki; Hayashi, Kenjiro; Yamakawa, Hiroki; Yamazoe, Yasushi; Yoshinari, Kouichi

    2015-01-01

    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  4. Physicochemical characteristics and gastrointestinal absorption behaviors of S-propargyl-cysteine, a potential new drug candidate for cardiovascular protection and antitumor treatment.

    PubMed

    Ma, Guo; Zhang, Lin; Zhang, Peng; Bao, Xingfei; Zhou, Ning; Shi, Qingling; Zheng, Yuanting; Liu, Hongrui; Bu, Fengjiao; Zhang, Ying; Huang, Wenjie; Wang, Fen; Zhu, Yizhun; Cai, Weimin

    2015-04-01

    1. As a potential new drug candidate for cardiovascular protection and antitumor treatment, the physicochemical properties, gastrointestinal (GI) absorption behaviors and mechanisms of S-propargyl-cysteine (SPRC) were investigated in this study. 2. SPRC exhibited favorable solubility in aqueous media. The log P and log D values were low (≤1.93 ± 0.08). The pKa in the acidic and basic regions was 2.08 ± 0.02 and 8.72 ± 0.03, respectively. The isoelectric point was 5.40 ± 0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and metabolism in the rat GI tract. 3. SPRC displayed poor gastric absorption and favorable intestinal absorption in the rat in situ GI perfusion model. Absorption rate constants (ka), hourly absorption percentage (P) and apparent permeability coefficient (Papp) of SPRC in the small intestine were ≥0.77 ± 0.06 h(-1), 59.25 ± 4.02% and (7.99 ± 0.88) × 10(-5 )cm/s, respectively. Absorption of SPRC exhibited a certain dependence on physiological pH and absorption region. Absorption of SPRC was not inhibited by l-methionine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. 4. SPRC showed favorable oral absorption. It can be categorized as a BCS class I drug. The membrane pore transport appeared to be one of the predominant absorption modes for SPRC.

  5. Aminoclay-lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption.

    PubMed

    Yang, Liang; Shao, Yating; Han, Hyo-Kyung

    2016-01-01

    This study aimed to prepare the aminoclay-lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay-lipid hybrid composite (ALC). The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w), krill oil to fenofibrate of 2:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (C max) and area under the curve (AUC) of fenofibric acid (an active metabolite) in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate.

  6. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    PubMed Central

    Yang, Liang; Shao, Yating; Han, Hyo-Kyung

    2016-01-01

    This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC). The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w), krill oil to fenofibrate of 2:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax) and area under the curve (AUC) of fenofibric acid (an active metabolite) in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. PMID:27042061

  7. Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

    PubMed

    Esteves, Freddy; Moutinho, Carla; Matos, Carla

    2013-06-01

    Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

  8. [Safe improvement of drug absorption by combinatorial use of sodium laurate with amino acids: cytoprotection by amino acids and its mechanisms].

    PubMed

    Higaki, Kazutaka

    2007-04-01

    The development of combinatorial chemistry and high-throughput screening techniques has made it possible to generate many new drug candidates very rapidly, but it has also resulted in a number of poorly soluble and/or poorly absorbable candidates. A new trend in drug development based on pharmacogenomics or the development of molecular-targeted drugs is also spurring the tendency, and it does not necessarily lead to good output in terms of the development of new drugs. It is attractive to improve membrane permeability as well as solubility by using adjuvants, because this method could be applicable for various drugs. However, the practical use of absorption-enhancing adjuvants has been limited because of the potential local toxicity. Therefore suppressing the potential local toxicity would lead to the successful development of safe preparations with improved absorption using adjuvants. Our biochemical and histopathologic studies showed that several amino acids such as taurine and L-glutamine had cytoprotective activity, and it has been found that the combinatorial use of sodium laurate (C12) with these amino acids could maintain the absorption-enhancing ability of C12. A suppository preparation containing C12 and taurine remarkably improved the rectal absorption of rebamipide, classified as BCS class IV, and the preparation was safe to the rectal mucosa. For the mechanisms of cytoprotective action by these amino acids, it has been found that they suppress the intracellular calcium level, induce the expression of heat-shock protein 70, and inhibit the release of histamine and apoptosis.

  9. A new in vitro system for evaluation of passive intestinal drug absorption: establishment of a double artificial membrane permeation assay.

    PubMed

    Kataoka, Makoto; Tsuneishi, Saki; Maeda, Yukako; Masaoka, Yoshie; Sakuma, Shinji; Yamashita, Shinji

    2014-11-01

    The aim of this present study was to establish a new in vitro assay, double artificial membrane permeation assay (DAMPA), to evaluate the human intestinal permeability of drugs. A double artificial membrane with an intracellular compartment was constructed in side-by-side chambers by sandwiching a filter containing buffer solution with impregnated lipophilic filters with dodecane containing 2w/v% phosphatidylcholine. Permeation data of ionic compounds clearly indicated that not only the pH value of the apical solution but also that of the intracellular compartment affected the permeability across the double artificial membrane. DAMPA was performed with 20 compounds at physiological pH (apical; 6.5, intracellular and basal; 7.4). Paracellular and transcellular permeabilities of compounds in human epithelium were estimated based on the characteristics of the paracellular pathway using physicochemical properties of compounds with the Renkin function and the area factor i.e. the difference in the effective surface area between human epithelium and the double artificial membrane, respectively. The human intestinal permeability of each compound was predicted by the sum of estimated transcellular and paracellular permeabilities. Predicted human intestinal permeability was significantly correlated with the fraction of absorbed dose in humans, indicating that DAMPA has the potential to predict oral absorption of drugs in humans.

  10. Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

    PubMed

    Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

    2015-12-01

    This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the P(app) and K(a) of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions.

  11. Justification of Drug Product Dissolution Rate and Drug Substance Particle Size Specifications Based on Absorption PBPK Modeling for Lesinurad Immediate Release Tablets.

    PubMed

    Pepin, Xavier J H; Flanagan, Talia R; Holt, David J; Eidelman, Anna; Treacy, Don; Rowlings, Colin E

    2016-09-06

    In silico absorption modeling has been performed, to assess the impact of in vitro dissolution on in vivo performance for ZURAMPIC (lesinurad) tablets. The dissolution profiles of lesinurad tablets generated using the quality control method were used as an input to a GastroPlus model to estimate in vivo dissolution in the various parts of the GI tract and predict human exposure. A model was set up, which accounts for differences of dosage form transit, dissolution, local pH in the GI tract, and fluid volumes available for dissolution. The predictive ability of the model was demonstrated by confirming that it can reproduce the Cmax observed for independent clinical trial. The model also indicated that drug product batches that pass the proposed dissolution specification of Q = 80% in 30 min are anticipated to be bioequivalent to the clinical reference batch. To further explore the dissolution space, additional simulations were performed using a theoretical dissolution profile below the proposed specification. The GastroPlus modeling indicates that such a batch will also be bioequivalent to standard clinical batches despite having a dissolution profile, which would fail the proposed dissolution specification of Q = 80% in 30 min. This demonstrates that the proposed dissolution specification sits comfortably within a region of dissolution performance where bioequivalence is anticipated and is not near an edge of failure for dissolution, providing additional confidence to the proposed specifications. Finally, simulations were performed using a virtual drug substance batch with a particle size distribution at the limit of the proposed specification for particle size. Based on these simulations, such a batch is also anticipated to be bioequivalent to clinical reference, demonstrating that the proposed specification limits for particle size distribution would give products bioequivalent to the pivotal clinical batches.

  12. Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

    PubMed

    Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing

    2016-11-01

    The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by (1)H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p <  0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

  13. Window cleaner poisoning

    MedlinePlus

    Older types of window cleaners may contain: Ammonia Ethanol Isopropyl alcohol Methanol New types of window cleaners ... pain Vomiting Vomiting blood HEART AND BLOOD Collapse Low blood pressure that develops rapidly LUNGS AND AIRWAYS ...

  14. Batteries: Widening voltage windows

    NASA Astrophysics Data System (ADS)

    Xu, Kang; Wang, Chunsheng

    2016-10-01

    The energy output of aqueous batteries is largely limited by the narrow voltage window of their electrolytes. Now, a hydrate melt consisting of lithium salts is shown to expand such voltage windows, leading to a high-energy aqueous battery.

  15. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    NASA Astrophysics Data System (ADS)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of "fluorine as a probe in medicinal chemistry" an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells.

  16. Window Replacement Tips.

    ERIC Educational Resources Information Center

    Wiens, Janet

    2001-01-01

    Explores ways to replace facility windows more easily and efficiently by evaluating long-term needs and window options. Recommends obtaining references from window manufacturer and installer, scheduling the work during times the facility is unoccupied, and ensuring that historic and life-safety issues be considered. (GR)

  17. Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism and Excretion Studies of a BDDCS II Drug.

    PubMed

    He, Handan; Tran, Phi; Gu, Helen; Tedesco, Vivienne; Zhang, Jin; Lin, Wen; Gatlik, Ewa; Klein, Kai; Heimbach, Tycho

    2017-03-07

    The absorption, metabolism and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50 mg [14C]midostaurin dose, oral absorption was high (> 90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 h), CGP52421 (495 h), and CGP62221 (33.4 h). Through careful mass-balance study design, the recovery achieved was good (81.6%), despite the long radioactivity half-lives. Most of the radioactive dose was recovered in feces (77.6%) mainly as metabolites; as only 3.43% was unchanged, suggesting mainly hepatic metabolism. Renal elimination was minor (4%). Midostaurin metabolism pathways involved hydroxylation, O demethylation, amide hydrolysis and N demethylation. High plasma CGP52421 and CGP62221 exposures in humans, along with relatively potent cell-based IC50 for FLT3-ITD inhibition, suggested that the antileukemic activity in AML patients may also be maintained by the metabolites. Very high plasma protein binding (>99%) required equilibrium gel filtration to identify differences between humans and animals. As midostaurin, CGP52421 and CGP62221 are metabolized mainly by CYP3A4 and are inhibitors/inducers for CYP3A, potential drug-drug interactions with mainly CYP3A4 modulators/CYP3A substrates could be expected. Given its low aqueous solubility, high oral absorption and extensive metabolism (> 90%), midostaurin is a BCS/BDDCS class II drug in human, consistent with rat BDDCS in vivo data showing high absorption (>90%) and extensive metabolism (>90%).

  18. Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption.

    PubMed

    Annaert, Pieter; Brouwers, Joachim; Bijnens, Ann; Lammert, Frank; Tack, Jan; Augustijns, Patrick

    2010-01-31

    The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, while the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults.

  19. Nonlinear absorption kinetics of self-emulsifying drug delivery systems (SEDDS) containing tocotrienols as lipophilic molecules: in vivo and in vitro studies.

    PubMed

    Alqahtani, Saeed; Alayoubi, Alaadin; Nazzal, Sami; Sylvester, Paul W; Kaddoumi, Amal

    2013-07-01

    Self-emulsifying drug delivery systems (SEDDS) have been broadly used to promote the oral absorption of poorly water-soluble drugs. The purpose of the current study was to evaluate the in vivo oral bioavailability of vitamin E isoforms, δ-tocotrienol (δ-T3) and γ-tocotrienol (γ-T3) administered as SEDDS, as compared to commercially available UNIQUE E® Tocotrienols capsules. Results from studies in rats showed that low dose treatment with δ-T3 (90%) and γ-T3 (10%) formulated SEDDS showed bioavailability of 31.5% and 332%, respectively. However, bioavailability showed a progressive decrease with increased treatment dose that displayed nonlinear absorption kinetics. Additional in vitro studies examining cellular uptake studies in Caco 2 cells revealed that the SEDDS formulation increased passive permeability of δ-T3 and γ-T3 by threefold as compared to the commercial capsule formulation. These studies also showed that free surfactants decreased δ-T3 and γ-T3 absorption. Specifically, combined treatment cremophor EL or labrasol with tocotrienols caused a 60-85% reduction in the cellular uptake of δ-T3 and γ-T3 and these effects appear to result from surfactant-induced inhibition of the δ-T3 and γ-T3 transport protein Niemann-Pick C1-like 1 (NPC1L1). In summary, results showed that SEDDS formulation significantly increases the absorption and bioavailability δ-T3 and γ-T3. However, this effect is self-limiting because treatment with increasing doses of SEDDS appears to be associated with a corresponding increase in free surfactants levels that directly and negatively impact tocotrienol transport protein function and results in nonlinear absorption kinetics and a progressive decrease in δ-T3 and γ-T3 absorption and bioavailability.

  20. Conformal ALON® windows

    NASA Astrophysics Data System (ADS)

    Goldman, Lee M.; Balasubramanian, Sreeram; Smith, Mark; Nag, Nagendra; Foti, Robyn; Jha, Santosh; Sastri, Suri

    2014-05-01

    Aluminum Oxynitride (ALON® Optical Ceramic) combines broadband transparency with excellent mechanical properties. ALON's cubic structure means that it is transparent in its polycrystalline form, allowing it to be manufactured by conventional powder processing techniques. Surmet controls every aspect of the manufacturing process, beginning with synthesis of ALON® powder, continuing through forming/heat treatment of blanks, ending with optical fabrication of ALON® windows. Surmet has made significant progress in its production capability in recent years. Additional scale up of Surmet's manufacturing capability, for complex geometries, larger sizes and higher quantities, is underway. The requirements for modern aircraft are driving the need for conformal windows for future sensor systems. However, limitations on optical systems and the ability to produce windows in complex geometries currently limit the geometry of existing windows and window assemblies to faceted assemblies of flat windows. Surmet's ability to produce large curved ALON® blanks is an important step in the development of conformal windows for future aircraft applications.

  1. Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system: in vitro and in vivo studies.

    PubMed

    Lv, Liang-Zhong; Tong, Chen-Qi; Lv, Qing; Tang, Xin-Jiang; Li, Li-Ming; Fang, Qing-Xia; Yu, Jia; Han, Min; Gao, Jian-Qing

    2012-01-01

    Hydroxysafflor yellow A (HSYA), the main active ingredient of the safflower plant (Carthamus tinctorius L.), is a hydrophilic drug with low oral bioavailability. Water-in-oil-in-water (w/o/w) double emulsions may enhance the oral absorption of HSYA. In this study, we prepared a self-double-emulsifying drug delivery system (SDEDDS) to improve the absorption of HSYA. SDEDDS consists of water in oil emulsions and hydrophilic surfactants that can self-emulsify into w/o/w double emulsions in the aqueous gastrointestinal environment. Confocal laser scanning micrographs showed that spherical droplets were uniformly distributed in the dispersion medium with narrow particle size distribution and could form fine w/o/w double emulsions upon dilution in dispersion medium with gentle stirring. The dispersed oil droplets contained small dispersed aqueous droplets consistent with the characteristics of double emulsions. Furthermore, in vitro cellular experiments were performed to study the mechanism of the absorption promoting effect of SDEDDS. The accumulation of rhodamine-123 in Caco-2 cells was used to evaluate the efflux transport of p-glycoprotein inhibitor. Histopathologic studies on the rat intestine showed that SDEDDS can cause mucosal damage to a certain degree of toxicity, however this was not serious. These results suggest that SDEDDS can greatly improve the oral absorption of HSYA. Given the toxicity demonstrated to the small intestine, the formulation prescription should be improved to enhance security in the future.

  2. Impaired drug absorption due to high stomach pH: a review of strategies for mitigation of such effect to enable pharmaceutical product development.

    PubMed

    Mitra, Amitava; Kesisoglou, Filippos

    2013-11-04

    Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.

  3. Evaluation of the use of Göttingen minipigs to predict food effects on the oral absorption of drugs in humans.

    PubMed

    Christiansen, Martin Lau; Müllertz, Anette; Garmer, Mats; Kristensen, Jakob; Jacobsen, Jette; Abrahamsson, Bertil; Holm, Rene

    2015-01-01

    This study investigated the oral absorption of drugs in minipigs to predict food effects in man. The protocol was based on a previously described model in dogs and further investigated the food source (i.e., US FDA breakfast or a nutritional drink) and food quantities. Two poorly soluble compounds were investigated [pravastatin (negative food effect) and atazanavir (positive food effect)] in Göttingen minipigs after seven different food regimens. The gastric emptying rate was evaluated by coadministration of acetaminophen. In short, the results demonstrated longer gastric emptying times in minipigs when compared with humans, within a range from 2.3 to 8.4 h dependent on the food regimen. There were no significant differences in drug absorption between fed and fasted state for the two compounds. The study showed that the dog protocol could not be transferred directly to minipigs, but needs further investigation and adjustments in order to get a valid model using Göttingen minipigs for the evaluation of food effects on drug absorption in humans.

  4. Low loss nitride ceramics for terahertz windows

    NASA Astrophysics Data System (ADS)

    Naftaly, M.; Greenslade, P. J.; Miles, R. E.; Evans, D.

    2009-09-01

    Terahertz frequency transmission measurements on ceramic boron nitride and aluminium nitride are described. The absorption coefficients and refractive indices of these materials show that they have high terahertz transparency, which together with their high melting temperatures and mechanical strength makes them particularly suitable for use as THz windows in high pressure and/or high temperature applications.

  5. LC-MS/MS determination and interaction of the main components from the traditional Chinese drug pair Danshen-Sanqi based on rat intestinal absorption.

    PubMed

    Huang, Juan; Zhang, Jing; Bai, Junqi; Xu, Wen; Wu, Dinghong; Qiu, Xiaohui

    2016-12-01

    The Chinese drug pair Danshen (Salvia miltiorrhiza)-Sanqi (Panax ginseng) has been widely used for centuries treating various cardiovascular disorders, among which salvianlic acid B (SAB), ginsenoside Rg1 (GRg1 ), ginsenoside Rb1 (GRb1 ) and notoginsenoside R1 (NGR1 ) were identified as the major components. The present study focused on the interaction between these components based on investigating their intestinal absorption using the Ussing chamber technique. The concentrations of SAB, GRg1 , GRb1 and NGR1 in the intestinal perfusate were determined by LC-MS/MS method, followed by Q (accumulative quantity) and Papp (apparent permeability). The results showed that all these four main components displayed very low permeabilities, which implied their poor absorption in the rat intestine. The intestinal absorption level of SAB displayed regioselectivity: duodenum < jejunum < ileum. However, there was no significant difference in the absorption of GRg1 and GRb1 in the different segments. The Q and Papp values of the four main components were obviously increased in jejunum when co-administrating Danshen extract with Sanqi extract. In conclusion, compatibility of Danshen and Sanqi could remarkably improve the intestinal absorption level of the main components in the pair. To some extent, this might explain the nature of the compatibility mechanisms of composite formulae in TCMs.

  6. The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

    PubMed

    Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

    2017-03-03

    The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and

  7. A Quantitative Review and Meta-models of the Variability and Factors Affecting Oral Drug Absorption-Part II: Gastrointestinal Transit Time.

    PubMed

    Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

    2016-09-01

    This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) transit times of non-disintegrating single-unit ("tablet") and multiple-unit ("pellets/multi-unit tablet") solid dosage forms, characterize the effect of food on the values and variability in these parameters and present quantitative meta-models of the distributions of GI transit times in the respective GI regions to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, gastric, small intestinal and colonic transit times under fed and fasted conditions. Meta-analysis used the "metafor" package of the R language. Meta-models of GI transit were assumed to be log-normally distributed between the studied populations. Twenty-nine studies including 125 reported means and standard deviations were used in the meta-analysis. Caloric content of administered food increased variability and delayed the gastric transit of both pellets and tablets. Conversely, food caloric content reduced the variability but had no significant influence on the mean small intestinal transit time (SITT). Food had no significant effect on the transit time through the colon. The transit of pellets through the colon was significantly slower than that of single-unit tablets which is most likely related to their smaller size. GI transit times may influence the dissolution and absorption of oral drugs. The meta-models of GI transit times may be used as part of semi-physiological absorption models to characterize the influence of transit time on the dissolution, absorption and in vivo pharmacokinetic profiles of oral drugs.

  8. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing : optimization of the applied dose for postoperative care.

    PubMed

    Chen, Wei-Yu; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Hung-Hsu; Li, Yi-Ching; Fang, Jia-You

    2013-09-01

    The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

  9. Studies on effective atomic numbers for photon energy absorption and electron density of some narcotic drugs in the energy range 1 keV-20 MeV

    NASA Astrophysics Data System (ADS)

    Gounhalli, Shivraj G.; Shantappa, Anil; Hanagodimath, S. M.

    2013-04-01

    Effective atomic numbers for photon energy absorption ZPEA,eff, photon interaction ZPI,eff and for electron density Nel, have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for narcotic drugs, such as Heroin (H), Cocaine (CO), Caffeine (CA), Tetrahydrocannabinol (THC), Cannabinol (CBD), Tetrahydrocannabivarin (THCV). The ZPEA,eff, ZPI,eff and Nel values have been found to change with energy and composition of the narcotic drugs. The energy dependence ZPEA,eff, ZPI,eff and Nel is shown graphically. The maximum difference between the values of ZPEA,eff, and ZPI,eff occurs at 30 keV and the significant difference of 2 to 33% for the energy region 5-100 keV for all drugs. The reason for these differences is discussed.

  10. Interaction of Nanostructured Calcium Silicate Hydrate with Ibuprofen Drug Molecules: X-ray Absorption Near Edge Structure (XANES) Study at the Ca, Si and O K-edge

    NASA Astrophysics Data System (ADS)

    Guo, X. X.; Sham, T. K.; Zhu, Y. J.; Hu, Y. F.

    2013-04-01

    Mesoporous calcium silicate hydrate (CSH) nanostructure has been proven to be bioactive and biocompatible, and has a bright future in the application of bone treatment among other applications. X-ray absorption near edge structure (XANES) is a powerful tool for the study of the interactions of calcium silicate hydrates with drug molecules because it is element specific and it probes the unoccupied electronic states. Herein, we report the use of the calcium, silicon and oxygen K-edge XANES spectroscopy to identify how drug molecules interact with different groups in calcium silicate hydrate mesoporous nano-carriers with different morphologies. Significant changes are observed in XANES spectra after drug loading into the calcium silicate hydrate system, especially at the Si and O K-edge. The implications of these findings are discussed.

  11. Development of a serum-free human cornea construct for in vitro drug absorption studies: the influence of varying cultivation parameters on barrier characteristics.

    PubMed

    Hahne, Matthias; Reichl, Stephan

    2011-09-15

    The increased use of ophthalmic products in recent years has led to an increased demand for in vitro and in vivo transcorneal drug absorption studies. Cell-culture models of the human cornea can avoid several of the disadvantages of widely used animal experimental models, including ethical concerns and poor standardisation. This study describes the development of a serum-free cultivated, three-dimensional human cornea model (Hemicornea, HC) for drug absorption experiments. The impact of varying cultivation conditions on the corneal barrier function was analysed and compared with excised rabbit and porcine corneas. The HC was cultivated on permeable polycarbonate filters using immortalised human keratocytes and a corneal epithelial cell line. The equivalence to native tissue was investigated through absorption studies using model substances with a wide range of molecular characteristics, including hydrophilic sodium fluorescein, lipophilic rhodamine B and fluorescein isothiocyanate (FITC)-labelled macromolecule dextran. To study the intra-laboratory repeatability and construct cultivation, the permeation studies were performed independently by different researchers. The HC exhibited a permeation barrier in the same range as excised animal corneas, high reproducibility and a lower standard deviation. Therefore, the HC could be a promising in vitro alternative to ex vivo corneal tissues in preclinical permeation studies.

  12. Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer.

    PubMed

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2016-02-01

    A human small intestinal epithelial cell (HIEC) monolayer was recently established in our laboratories as a novel system to evaluate the Papp (apparent permeability coefficient) of compounds during their absorption in humans. An effusion-based analysis using polyethylene glycol oligomers with molecular weights ranging from 194-898 indicated that HIEC and Caco-2 cell monolayers both had paracellular pores with 2 distinct radiuses (∼ 5 and 9-14 Å), whereas the porosity of large pores was 11-fold higher in the HIEC monolayer (44 × 10(-8)) than in the Caco-2 cells (4 × 10(-8)). A comparison between the fraction-absorbed (Fa) values observed in humans and those predicted from Papp values in both monolayers indicated that the HIEC monolayer had markedly higher precision to predict Fa values with root mean square error of 9.40 than the Caco-2 cells (root mean square error = 16.90) for 10 paracellularly absorbed compounds. Furthermore, the accuracy of the HIEC monolayer to classify the absorption of 23 test drugs with diverse absorption properties, including different pathways in the presence or absence of susceptibility to efflux transporters, was higher than that of the Caco-2 cell monolayer. In conclusion, the HIEC monolayer exhibited advantages over Caco-2 cells in the ranking and prediction of absorption of compounds in humans.

  13. Color Wheel Windows

    ERIC Educational Resources Information Center

    Leonard, Stephanie

    2012-01-01

    In this article, the author describes a painting and drawing lesson which was inspired by the beautiful circular windows found in cathedrals and churches (also known as "rose windows"). This two-week lesson would reinforce both the concept of symmetry and students' understanding of the color wheel. (Contains 1 online resource.)

  14. Efficient Windows Collaborative

    SciTech Connect

    Nils Petermann

    2010-02-28

    The project goals covered both the residential and commercial windows markets and involved a range of audiences such as window manufacturers, builders, homeowners, design professionals, utilities, and public agencies. Essential goals included: (1) Creation of 'Master Toolkits' of information that integrate diverse tools, rating systems, and incentive programs, customized for key audiences such as window manufacturers, design professionals, and utility programs. (2) Delivery of education and outreach programs to multiple audiences through conference presentations, publication of articles for builders and other industry professionals, and targeted dissemination of efficient window curricula to professionals and students. (3) Design and implementation of mechanisms to encourage and track sales of more efficient products through the existing Window Products Database as an incentive for manufacturers to improve products and participate in programs such as NFRC and ENERGY STAR. (4) Development of utility incentive programs to promote more efficient residential and commercial windows. Partnership with regional and local entities on the development of programs and customized information to move the market toward the highest performing products. An overarching project goal was to ensure that different audiences adopt and use the developed information, design and promotion tools and thus increase the market penetration of energy efficient fenestration products. In particular, a crucial success criterion was to move gas and electric utilities to increase the promotion of energy efficient windows through demand side management programs as an important step toward increasing the market share of energy efficient windows.

  15. Air transparent soundproof window

    NASA Astrophysics Data System (ADS)

    Kim, Sang-Hoon; Lee, Seong-Hyun

    2014-11-01

    A soundproof window or wall which is transparent to airflow is presented. The design is based on two wave theories: the theory of diffraction and the theory of acoustic metamaterials. It consists of a three-dimensional array of strong diffraction-type resonators with many holes centered on each individual resonator. The negative effective bulk modulus of the resonators produces evanescent wave, and at the same time the air holes with subwavelength diameter existed on the surfaces of the window for macroscopic air ventilation. The acoustic performance levels of two soundproof windows with air holes of 20mm and 50mm diameters were measured. The sound level was reduced by about 30 - 35dB in the frequency range of 400 - 5,000Hz with the 20mm window, and by about 20 - 35dB in the frequency range of 700 - 2,200Hz with the 50mm window. Multi stop-band was created by the multi-layers of the window. The attenuation length or the thickness of the window was limited by background noise. The effectiveness of the soundproof window with airflow was demonstrated by a real installation.

  16. Air transparent soundproof window

    SciTech Connect

    Kim, Sang-Hoon; Lee, Seong-Hyun

    2014-11-15

    A soundproof window or wall which is transparent to airflow is presented. The design is based on two wave theories: the theory of diffraction and the theory of acoustic metamaterials. It consists of a three-dimensional array of strong diffraction-type resonators with many holes centered on each individual resonator. The negative effective bulk modulus of the resonators produces evanescent wave, and at the same time the air holes with subwavelength diameter existed on the surfaces of the window for macroscopic air ventilation. The acoustic performance levels of two soundproof windows with air holes of 20mm and 50mm diameters were measured. The sound level was reduced by about 30 - 35dB in the frequency range of 400 - 5,000Hz with the 20mm window, and by about 20 - 35dB in the frequency range of 700 - 2,200Hz with the 50mm window. Multi stop-band was created by the multi-layers of the window. The attenuation length or the thickness of the window was limited by background noise. The effectiveness of the soundproof window with airflow was demonstrated by a real installation.

  17. Impact of excipient interactions on drug bioavailability from solid dosage forms.

    PubMed

    Panakanti, Ravikiran; Narang, Ajit S

    2012-10-01

    Excipients are generally pharmacologically inert, but can interact with drugs in the dosage form and the physiological factors at the site of absorption to affect the bioavailability of a drug product. A general mechanistic understanding of the basis of these interactions is essential to design robust drug products. This paper focuses on drug-excipient interactions in solid dosage forms that impact drug bioavailability, the drug substance and drug product properties affected by excipients, and the impact of excipients on physiologic processes. The extent to which drug bioavailability is affected by these interactions would vary on a case-by-case basis depending upon factors such as the potency and dose of the drug, therapeutic window, site of absorption, rate limiting factor in drug absorption (e.g., permeability or solubility limited), or whether drug metabolism, efflux, complexation, or degradation at the site of absorption play a role in determining its bioavailability. Nonetheless, a mechanistic understanding of drug-excipient interactions and their impact on drug release and absorption can help develop formulations that exhibit optimum drug bioavailability.

  18. Multi-functional windows

    NASA Astrophysics Data System (ADS)

    Nag, Nagendra; Goldman, Lee M.; Balasubramanian, Sreeram; Sastri, Suri

    2013-06-01

    The requirements for modern aircraft are driving the need for conformal windows for future sensor systems. However, limitations on optical systems and the physical properties of optically transparent materials currently limit the geometry of existing windows and window assemblies to faceted assemblies of flat windows held in weight bearing frames. Novel material systems will have to be developed which combine different materials (e.g. ductile metals with transparent ceramics) into structures that combine transparency with structural integrity. Surmet's demonstrated ability to produce novel transparent ceramic/metal structures will allow us to produce such structures in the types of conformal shapes required for future aircraft applications. Furthermore, the ability to incorporate transparencies into such structures also holds out the promise of creating multi-functional windows which provide a broad range of capabilities that might include RF antennas and de-icing in addition to transparency. Recent results in this area will be presented.

  19. Windows technology assessment

    SciTech Connect

    Baron, J.J.

    1995-10-01

    This assessment estimates that energy loss through windows is approximately 15 percent of all the energy used for space heating and cooling in residential and commercial buildings in New York State. The rule of thumb for the nation as a whole is about 25 percent. The difference may reflect a traditional assumption of single-pane windows while this assessment analyzed installed window types in the region. Based on the often-quoted assumption, in the United States some 3.5 quadrillion British thermal units (Btu) of primary energy, costing some $20 billion, is annually consumed as a result of energy lost through windows. According to this assessment, in New York State, the energy lost due to heat loss through windows is approximately 80 trillion Btu at an annual cost of approximately $1 billion.

  20. Improved Oral Bioavailability of Lacidipine Using Nanosuspension Technology: Inferior in vitro Dissolution and Superior in vivo Drug Absorption versus Lacipil®.

    PubMed

    Zhao, Juanhang; Luo, Lei; Fu, Qiang; Guo, Bei; Li, Yun; Geng, Yajie; Wang, Junfeng; Zhang, Tianhong

    2016-01-01

    Improved dissolution is a better way of increasing the oral absorption of lacidipine (LCDP) because it is a BCS II class drug. The purpose of this study is to improve the oral bioavailability of LCDP by applying nanosuspension technology. LCDP nanosuspensions were prepared by a hybrid method of microprecipitation and high pressure homogenization. The effects of the production parameters (shearing rate and time, the stabilizers and their concentrations, homogenization pressure and number of cycles) were investigated to optimize the preparation process. In vitro characterizations (X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy and dissolution measurement) were carried out and an oral pharmacokinetic study was performed in beagle dogs. LCDP was transformed into an amorphous state during the preparation process, and the mean particle size was about 714.0 ± 12.7 nm. The dissolution rate of LCDP nanosuspensions was faster than that of physical mixtures, but slower than that of Lacipil® (the commercial tablet). Regarding the in vivo pharmacokinetics, the key pharmacokinetic parameters (Cmax and AUC0-∞) of the nanosuspensions were statistically significantly higher than those of both the commercial tablet and physical mixtures. So, this is an efficient drug delivery strategy to facilitate the oral administration of LCDP by using nanosuspension technology, and should be generally applicable to many poorly water-soluble drugs with dissolution rate-limited absorption.

  1. Zero Energy Windows

    SciTech Connect

    Arasteh, Dariush; Selkowitz, Steve; Apte, Josh; LaFrance, Marc

    2006-05-17

    Windows in the U.S. consume 30 percent of building heating and cooling energy, representing an annual impact of 4.1 quadrillion BTU (quads) of primary energy. Windows have an even larger impact on peak energy demand and on occupant comfort. An additional 1 quad of lighting energy could be saved if buildings employed effective daylighting strategies. The ENERGY STAR{reg_sign} program has made standard windows significantly more efficient. However, even if all windows in the stock were replaced with today's efficient products, window energy consumption would still be approximately 2 quads. However, windows can be ''net energy gainers'' or ''zero-energy'' products. Highly insulating products in heating applications can admit more useful solar gain than the conductive energy lost through them. Dynamic glazings can modulate solar gains to minimize cooling energy needs and, in commercial buildings, allow daylighting to offset lighting requirements. The needed solutions vary with building type and climate. Developing this next generation of zero-energy windows will provide products for both existing buildings undergoing window replacements and products which are expected to be contributors to zero-energy buildings. This paper defines the requirements for zero-energy windows. The technical potentials in terms of national energy savings and the research and development (R&D) status of the following technologies are presented: (1) Highly insulating systems with U-factors of 0.1 Btu/hr-ft{sup 2}-F; (2) Dynamic windows: glazings that modulate transmittance (i.e., change from clear to tinted and/or reflective) in response to climate conditions; and (3) Integrated facades for commercial buildings to control/ redirect daylight. Market transformation policies to promote these technologies as they emerge into the marketplace are then described.

  2. The Efficient Windows Collaborative

    SciTech Connect

    Petermann, Nils

    2006-03-31

    The Efficient Windows Collaborative (EWC) is a coalition of manufacturers, component suppliers, government agencies, research institutions, and others who partner to expand the market for energy efficient window products. Funded through a cooperative agreement with the U.S. Department of Energy, the EWC provides education, communication and outreach in order to transform the residential window market to 70% energy efficient products by 2005. Implementation of the EWC is managed by the Alliance to Save Energy, with support from the University of Minnesota and Lawrence Berkeley National Laboratory.

  3. double hung window details, hall window details, entrance door profiles ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    double hung window details, hall window details, entrance door profiles - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Help's Quarters, Prince William Forest Park, Triangle, Prince William County, VA

  4. Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans.

    PubMed

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2014-11-01

    Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As a novel in vitro system for the evaluation of drug absorption, we characterized a human small intestinal epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation from ISCs consistently conferred the capability of maturation of enterocytes to HIECs over 25 passages. The morphologically matured HIEC monolayer consisted of polarized columnar epithelia with dense microvilli, tight junctions, and desmosomes 8 days after seeding onto culture inserts. Transepithelial electrical resistance across the monolayer was 9-fold lower in HIECs (98.9 Ω × cm(2)) than in Caco-2 cells (900 Ω × cm(2)), which indicated that the looseness of the tight junctions in the HIEC monolayer was similar to that in the human small intestine (approximately 40 Ω × cm(2)). No significant differences were observed in the overall gene expression patterns of the major drug-metabolizing enzymes and transporters between the HIEC and Caco-2 cell monolayers. Furthermore, the functions of P-glycoprotein and breast cancer resistance protein in the HIEC monolayer were confirmed by the vectorial transport of marker substrates and their disappearance in the presence of specific inhibitors. The apparent drug permeability values of paracellularly transported compounds (fluorescein isothiocyanate-dextran 4000, atenolol, and terbutaline) and nucleoside transporter substrates (didanosine, ribavirin, and doxifluridine) in the HIEC monolayer were markedly higher than those of Caco-2 cells, whereas transcellularly transported drugs (pindolol and midazolam) were equally well permeated. In conclusion, the HIEC monolayer can serve as a novel and superior alternative to the conventional Caco-2 cell monolayer for predicting oral absorption in humans.

  5. Nutrient absorption.

    PubMed

    Rubin, Deborah C

    2004-03-01

    Our understanding of nutrient absorption continues to grow, from the development of unique animal models and from studies in which cutting-edge molecular and cellular biologic approaches have been used to analyze the structure and function of relevant molecules. Studies of the molecular genetics of inherited disorders have also provided many new insights into these processes. A major advance in lipid absorption has been the cloning and characterization of several intestinal acyl CoA:monoacylglycerol acyltransferases; these may provide new targets for antiobesity drug therapy. Studies of intestinal cholesterol absorption and reverse cholesterol transport have encouraged the development of novel potential treatments for hyperlipidemia. Observations in genetically modified mice and in humans with mutations in glucose transporter 2 suggest the importance of a separate microsomal membrane transport pathway for glucose transport. The study of iron metabolism has advanced greatly with the identification of the hemochromatosis gene and the continued examination of the genetic regulation of iron absorptive pathways. Several human thiamine transporters have been identified, and their specific roles in different tissues are being explored.

  6. Superconductive radiofrequency window assembly

    DOEpatents

    Phillips, H.L.; Elliott, T.S.

    1998-05-19

    The present invention is a superconducting radiofrequency window assembly for use in an electron beam accelerator. The SRF window assembly has a superconducting metal-ceramic design. The SRF window assembly comprises a superconducting frame, a ceramic plate having a superconducting metallized area, and a superconducting eyelet for sealing plate into frame. The plate is brazed to eyelet which is then electron beam welded to frame. A method for providing a ceramic object mounted in a metal member to withstand cryogenic temperatures is also provided. The method involves a new metallization process for coating a selected area of a ceramic object with a thin film of a superconducting material. Finally, a method for assembling an electron beam accelerator cavity utilizing the SRF window assembly is provided. The procedure is carried out within an ultra clean room to minimize exposure to particulates which adversely affect the performance of the cavity within the electron beam accelerator. 11 figs.

  7. Superconducting radiofrequency window assembly

    DOEpatents

    Phillips, H.L.; Elliott, T.S.

    1997-03-11

    The present invention is a superconducting radiofrequency window assembly for use in an electron beam accelerator. The srf window assembly has a superconducting metal-ceramic design. The srf window assembly comprises a superconducting frame, a ceramic plate having a superconducting metallized area, and a superconducting eyelet for sealing plate into frame. The plate is brazed to eyelet which is then electron beam welded to frame. A method for providing a ceramic object mounted in a metal member to withstand cryogenic temperatures is also provided. The method involves a new metallization process for coating a selected area of a ceramic object with a thin film of a superconducting material. Finally, a method for assembling an electron beam accelerator cavity utilizing the srf window assembly is provided. The procedure is carried out within an ultra clean room to minimize exposure to particulates which adversely affect the performance of the cavity within the electron beam accelerator. 11 figs.

  8. Intelligent Thermochromic Windows

    NASA Astrophysics Data System (ADS)

    Parkin, Ivan P.; Manning, Troy D.

    2006-03-01

    This article covers the background and related science associated with a thermochromic window. A thermochromic window is a device that changes its reflectance and transmission properties at a specific critical temperature. At this temperature the material undergoes a semiconductor-to-metal transition—at low temperature the window will let in all of the sun's energy while above the critical temperature it will reflect the infrared portion of the sun's energy. Hence a thermochromic window could be used to significantly reduce air conditioning costs, which has consequential positive benefit in reducing electricity consumption and hence green house gas emissions. This article details the underlying science in making a new thin-film thermochromic coating by chemical vapor deposition; it describes the underlying physical chemistry associated with the semiconductor-to-metal transition and shows how substitutional doping within a crystal lattice can be used to lower the thermochromic switching temperature.

  9. Cordilleran slab windows

    SciTech Connect

    Thorkelson, D.J.; Taylor, R.P. )

    1989-09-01

    The geometry and geologic implications of subducted spreading ridges are topics that have bedeviled earth scientists ever since the recognition of plate tectonics. As a consequence of subduction of the Kula-Farallon and East Pacific rises, slab windows formed and migrated beneath the North American Cordillera. The probable shape and extent of these windows, which represent the asthenosphere-filled gaps between two separating, subducting oceanic plates, are depicted from the Late Cretaceous to the present. Possible effects of the existence and migration of slab windows on the Cordillera at various times include cessation of arc volcanism and replacement by rift or plate-edge volcanism; lithospheric uplift, attenuation, and extension; and increased intensity of compressional tectonism. Eocene extensional tectonism and alkaline magmatism in southern British Columbia and the northwestern United States were facilitated by slab-window development.

  10. Effects of phosphate binders on the gastrointestinal absorption of arsenate and of an SGLT2 inhibitor drug on the urinary excretion of arsenite in mice.

    PubMed

    Poór, Miklós; Németi, Balázs; Gregus, Zoltán

    2017-01-01

    Arsenate (As(V)) and arsenite (As(III)) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because As(V) mimics phosphate, phosphate binder drugs may decrease the intestinal As(V) absorption. Indeed, lanthanum and aluminium salts and sevelamer removed As(V) from solution in vitro, especially at acidic pH. In mice gavaged with As(V), lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of As(V) and its metabolites, indicating that they decreased the gastrointestinal As(V) absorption. As some glucose transporters may carry As(III), the effect of the SGLT2 inhibitor dapagliflozin was investigated in As(III)-injected mice. While producing extreme glucosuria, dapagliflozin barely affected the urinary excretion and tissue concentrations of As(III) and its metabolites. Thus, phosphate binders (especially lanthanum compounds) can reduce the gastrointestinal absorption of As(V); however, SGLT2 inhibition cannot diminish the renal reabsorption of As(III).

  11. Determination of drug absorption rate in time-variant disposition by direct deconvolution using beta clearance correction and end-constrained non-parametric regression.

    PubMed

    Neelakantan, S; Veng-Pedersen, P

    2005-11-01

    A novel numerical deconvolution method is presented that enables the estimation of drug absorption rates under time-variant disposition conditions. The method involves two components. (1) A disposition decomposition-recomposition (DDR) enabling exact changes in the unit impulse response (UIR) to be constructed based on centrally based clearance changes iteratively determined. (2) A non-parametric, end-constrained cubic spline (ECS) input response function estimated by cross-validation. The proposed DDR-ECS method compensates for disposition changes between the test and the reference administrations by using a "beta" clearance correction based on DDR analysis. The representation of the input response by the ECS method takes into consideration the complex absorption process and also ensures physiologically realistic approximations of the response. The stability of the new method to noisy data was evaluated by comprehensive simulations that considered different UIRs, various input functions, clearance changes and a novel scaling of the input function that includes the "flip-flop" absorption phenomena. The simulated input response was also analysed by two other methods and all three methods were compared for their relative performances. The DDR-ECS method provides better estimation of the input profile under significant clearance changes but tends to overestimate the input when there were only small changes in the clearance.

  12. Daylight Redirecting Window Film

    DTIC Science & Technology

    2013-12-01

    EW-201014) Daylight Redirecting Window Film December 2013 This document has been cleared for public release; Distribution...DEC 2013 2. REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Daylight Redirecting Window Film 5a. CONTRACT NUMBER...CCE cost of conserved energy DoD Department of Defense DRF daylight redirecting film EPA U.S. Environmental Protection Agency ESTCP

  13. Effect of Gastric Fluid Volume on the In Vitro Dissolution and In Vivo Absorption of BCS Class II Drugs: a Case Study with Nifedipine.

    PubMed

    Nader, Ahmed M; Quinney, Sara K; Fadda, Hala M; Foster, David R

    2016-07-01

    Nifedipine is a BCS Class II drug used for treatment of hypertension and preterm labor. Large inter-patient variability in nifedipine absorption results in variable exposure among different patients. We conducted in vitro dissolution studies to compare nifedipine dissolution from immediate release (IR) capsules with different volumes of dissolution media. Results from dissolution studies were used to design a crossover study in healthy volunteers to evaluate the effect of coadministered water volume with nifedipine 10 mg IR capsules on nifedipine pharmacokinetics, especially absorption (C max, t max, and AUC0-6). Dissolution studies demonstrated that larger gastric fluid volumes result in enhanced nifedipine dissolution from 10 mg IR cosolvent capsules (73 vs. 17% in 200 and 100 mL simulated gastric fluid, respectively, at 30 min). The pharmacokinetic crossover study in healthy volunteers (N = 6) did not show a significant effect of the water volume administered with the capsule (50 vs. 250 mL) on C max, t max, or AUC0-6 of orally administered nifedipine IR capsules (10 mg). However, administration of large water volumes resulted in lower variability in nifedipine C max (47 vs. 70% for 250 and 50 mL, respectively). Administration of large water volumes with nifedipine 10 mg IR cosolvent capsules may reduce inter-individual variability in plasma exposure. Evaluation of similar effects in other BCS Class II drugs is recommended.

  14. High Performance Window Retrofit

    SciTech Connect

    Shrestha, Som S; Hun, Diana E; Desjarlais, Andre Omer

    2013-12-01

    The US Department of Energy (DOE) Office of Energy Efficiency and Renewable Energy (EERE) and Traco partnered to develop high-performance windows for commercial building that are cost-effective. The main performance requirement for these windows was that they needed to have an R-value of at least 5 ft2 F h/Btu. This project seeks to quantify the potential energy savings from installing these windows in commercial buildings that are at least 20 years old. To this end, we are conducting evaluations at a two-story test facility that is representative of a commercial building from the 1980s, and are gathering measurements on the performance of its windows before and after double-pane, clear-glazed units are upgraded with R5 windows. Additionally, we will use these data to calibrate EnergyPlus models that we will allow us to extrapolate results to other climates. Findings from this project will provide empirical data on the benefits from high-performance windows, which will help promote their adoption in new and existing commercial buildings. This report describes the experimental setup, and includes some of the field and simulation results.

  15. Targeting SVCT for enhanced drug absorption: Synthesis and in vitro evaluation of a novel vitamin C conjugated prodrug of saquinavir

    PubMed Central

    Luo, Shuanghui; Wang, Zhiying; Patel, Mitesh; Khurana, Varun; Zhu, Xiaodong; Pal, Dhananjay; Mitra, Ashim. K.

    2015-01-01

    In order to improve oral absorption, a novel prodrug of saquinavir (Saq), ascorbyl-succinic-saquinavir (AA-Su-Saq) targeting sodium dependent vitamin C transporter (SVCT) was synthesized and evaluated. Aqueous solubility, stability and cytotoxicity were determined. Affinity of AA-Su-Saq towards effluxpump P-glycoprotein (P-gp) and recognition of AA-Su-Saq by SVCT were studied. Transepithelial permeability across polarized MDCK-MDR1 and Caco-2 cells were determined. Metabolic stability of AA-Su-Saq in rat liver microsomes was investigated. AA-Su-Saq appears to be fairly stable in both DPBS and Caco-2 cells with half lives of 9.65 and 5.73 h, respectively. Uptake of [3H]Saquinavir accelerated by 2.7 and 1.9 fold in the presence of 50 μM Saq and AA-Su-Saq in MDCK-MDR1 cells. Cellular accumulation of [14C]AA diminished by about 50–70% relative to control in the presence of 200 μM AA-Su-Saq in MDCK-MDR1 and Caco-2 cells. Uptake of AA-Su-Saq was lowered by 27% and 34% in the presence of 5 mM AA in MDCK-MDR1 and Caco-2 cells, respectively. Absorptive permeability of AA-Su-Saq was elevated about 4-5 fold and efflux index reduced by about 13-15 fold across the polarized MDCK-MDR1 and Caco-2 cells. Absorptive permeability of AA-Su-Saq decreased 44% in the presence of 5 mM AA across MDCK-MDR1 cells. AA-Su-Saq was devoid of cytotoxicity over the concentration range studied. AA-Su-Saq significantly enhanced the metabolic stability but lowered the affinity towards CYP3A4. In conclusion, prodrug modification of Saq through conjugation to AA via a linker significantly raised the absorptive permeability and metabolic stability. Such modification also caused significant evading of P-gp mediated efflux and CYP3A4 mediated metabolism. SVCT targeted prodrug approach can be an attractive strategy to enhance the oral absorption and systemic bioavailability of anti-HIV protease inhibitors. PMID:21571053

  16. The effect of macrophage and angiogenesis inhibition on the drug release and absorption from an intramuscular sustained-release paliperidone palmitate suspension.

    PubMed

    Darville, Nicolas; van Heerden, Marjolein; Mariën, Dirk; De Meulder, Marc; Rossenu, Stefaan; Vermeulen, An; Vynckier, An; De Jonghe, Sandra; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

    2016-05-28

    The intramuscular (IM) administration of long-acting injectable (LAI) aqueous nano-/microsuspensions elicits a chronic granulomatous injection site reaction, which recently has been hypothesized to drive the (pro)drug dissolution and systemic absorption resulting in flip-flop pharmacokinetics. The goal of this mechanistic study was to investigate the effects of the local macrophage infiltration and angiogenesis on the systemic drug exposure following a single IM administration of a paliperidone palmitate (PP) LAI nano-/microsuspension in the rat. Liposomal clodronate (CLO) and sunitinib (SNT) were co-administered to inhibit the depot infiltration and nano-/microparticle phagocytosis by macrophages, and the neovascularization of the depot, respectively. Semi-quantitative histopathology of the IM administration sites at day 1, 3, 7, 14, 21 and 28 after dosing with PP-LAI illustrated that CLO significantly decreased the rate and extent of the granulomatous inflammatory reaction. The macrophage infiltration was slowed down, but only partially suppressed by CLO and this translated in paliperidone (PAL) plasma concentration-time profiles that resembled those observed upon injection of PP-LAI only, albeit with a lower PAL input rate and delayed maximum plasma concentration (CMAX). Conversely, SNT treatment completely suppressed the granulomatous reaction, besides effectively inhibiting the neovascularization of the PP-LAI depot. This resulted in an even slower systemic PAL input with delayed and lower maximum PAL CMAX. The reduced PP-LAI lymph node retention after CLO and SNT treatment, as well as pharmacokinetic drug-drug interactions were rejected as possible sources of the observed pharmacokinetic differences. The biphasic PAL plasma concentration-time profiles could best be described by an open first-order disposition model with parallel fast (first-order) and slow (sequential zero-first-order) absorption. The correlation of the pharmacokinetic data with the

  17. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  18. Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs

    PubMed Central

    Rao, Shasha; Song, Yunmei; Peddie, Frank; Evans, Allan M

    2011-01-01

    Poorly water-soluble drugs, such as phenylephrine, offer challenging problems for buccal drug delivery. In order to overcome these problems, particle size reduction (to the nanometer range) and cyclodextrin complexation were investigated for permeability enhancement. The apparent solubility in water and the buccal permeation of the original phenylephrine coarse powder, a phenylephrine–cyclodextrin complex and phenylephrine nanosuspensions were characterized. The particle size and particle surface properties of phenylephrine nanosuspensions were used to optimize the size reduction process. The optimized phenylephrine nanosuspension was then freeze dried and incorporated into a multi-layered buccal patch, consisting of a small tablet adhered to a mucoadhesive film, yielding a phenylephrine buccal product with good dosage accuracy and improved mucosal permeability. The design of the buccal patch allows for drug incorporation without the need to change the mucoadhesive component, and is potentially suited to a range of poorly water-soluble compounds. PMID:21753876

  19. A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption-Part I: Gastrointestinal pH.

    PubMed

    Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

    2016-09-01

    This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) pH in the different GI segments; characterize the effect of food on the values and variability in these parameters; and present quantitative meta-models of distributions of GI pH to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions. The GI tract was categorized into the following 10 distinct regions: stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and ileum (proximal, mid, and distal small intestine), and colon (ascending, transverse, and descending colon). Meta-analysis used the "metafor" package of the R language. The time course of postprandial stomach pH was modeled using NONMEM. Food significantly influenced the estimated meta-mean stomach and duodenal pH but had no significant influence on small intestinal and colonic pH. The time course of postprandial pH was described using an exponential model. Increased meal caloric content increased the extent and duration of postprandial gastric pH buffering. The different parts of the small intestine had significantly different pH. Colonic pH was significantly different for descending but not for ascending and transverse colon. Knowledge of GI pH is important for the formulation design of the pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH may also be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics.

  20. Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls.

    PubMed

    Papich, Mark G; Martinez, Marilyn N

    2015-07-01

    The Biopharmaceutical Classification System (BCS) has been a prognostic tool for assessing the potential effects of formulation on the human drug oral bioavailability. When used in conjunction with in vitro dissolution tests, the BCS can support the prediction of in vivo product performance and the development of mechanistic models that support formulation assessments through the generation of "what if" scenarios. To date, the applicability of existing human BCS criteria has not been evaluated in dogs, thereby limiting its use in canine drug development. Therefore, we examined 50 drugs for which absolute bioavailability (F) was available both in dogs and humans. The drugs were also evaluated for any potential association between solubility (calculated from the dose number, Do) or lipophilicity (LogP) and F in dogs. In humans, solubility is determined in 250 mL of fluid. However, the appropriate volume for classifying drug solubility in dogs has not been established. In this analysis, the estimated volume of a water flush administered to fasted dogs (6 mL) and a volume of 250 mL scaled to a Beagle dog (35 mL) were examined. In addition, in humans, a Do value greater than 1.0 is used to define a compound as highly soluble and a LogP value greater than 1.72 as high permeability. These same criteria were applied for defining highly soluble and highly permeable in dogs. Whether using 35 or 6 mL to determine Do, the canine solubility classification remained unchanged for all but seven compounds. There were no clear associations between a drug's F in dogs and humans or between the canine value of F and either its human BCS classification, its LogP value, or the canine Do estimate. There was a tendency for those drugs with canine values of F equal to or greater than 80% to have LogP values equal to or greater than 1.0. Exceptions to this observation tended to be those compounds known to be absorbed via mechanisms other than passive diffusion (e.g., via transporters or

  1. Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled-release system and as a suspension of 15N-labelled drug to healthy volunteers.

    PubMed

    Wilding, I R; Davis, S S; Hardy, J G; Robertson, C S; John, V A; Powell, M L; Leal, M; Lloyd, P; Walker, S M

    1991-11-01

    1. Plasma drug concentrations after a single oral administration of a suspension of carbamazepine (CBZ) and a 20/200 CBZ Oros osmotic pump system were measured in eight healthy male volunteers. The oral suspension contained 100 mg CBZ labelled with the stable isotope nitrogen-15, whilst the Oros contained 200 mg unlabelled CBZ. Plasma concentrations of [15N]-CBZ and CBZ were measured simultaneously by gas chromatography-mass spectrometry. 2. The position of the CBZ Oros (labelled with indium-111) in the gastrointestinal tract was followed by gamma scintigraphy. Plasma drug concentrations after the two treatments were used to relate pharmacokinetic with transit data. 3. The Oros was taken after breakfast and gastric emptying occurred between 1.1- greater than h post-dosing (median, 5.3 h). Small intestinal transit times ranged from 1.5- greater than 3.6 h, with a median of 2.2 h. There were wide individual variations in colonic transit, and the total transit time ranged from 10-60 h (median, 22 h). 4. Relative systemic bioavailability of CBZ from the Oros was reduced compared with that from the suspension (mean dose normalised AUC ratio = 0.69 +/- 0.17; mean dose-normalised AUC ratio = 0.85 +/- 0.13, allowing for actual release from the Oros system). 5. The in vivo absorption of drug into the systemic circulation from the Oros was estimated using the Wagner-Nelson method. This showed that absorption of CBZ was rapid when the Oros was present in the stomach and small intestine, the rate being determined by the release of drug from the system.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. High performance sapphire windows

    NASA Technical Reports Server (NTRS)

    Bates, Stephen C.; Liou, Larry

    1993-01-01

    High-quality, wide-aperture optical access is usually required for the advanced laser diagnostics that can now make a wide variety of non-intrusive measurements of combustion processes. Specially processed and mounted sapphire windows are proposed to provide this optical access to extreme environment. Through surface treatments and proper thermal stress design, single crystal sapphire can be a mechanically equivalent replacement for high strength steel. A prototype sapphire window and mounting system have been developed in a successful NASA SBIR Phase 1 project. A large and reliable increase in sapphire design strength (as much as 10x) has been achieved, and the initial specifications necessary for these gains have been defined. Failure testing of small windows has conclusively demonstrated the increased sapphire strength, indicating that a nearly flawless surface polish is the primary cause of strengthening, while an unusual mounting arrangement also significantly contributes to a larger effective strength. Phase 2 work will complete specification and demonstration of these windows, and will fabricate a set for use at NASA. The enhanced capabilities of these high performance sapphire windows will lead to many diagnostic capabilities not previously possible, as well as new applications for sapphire.

  3. Evaluation of infrared-reflection absorption spectroscopy measurement and locally weighted partial least-squares for rapid analysis of residual drug substances in cleaning processes.

    PubMed

    Nakagawa, Hiroshi; Tajima, Takahiro; Kano, Manabu; Kim, Sanghong; Hasebe, Shinji; Suzuki, Tatsuya; Nakagami, Hiroaki

    2012-04-17

    The usefulness of infrared-reflection absorption spectroscopy (IR-RAS) for the rapid measurement of residual drug substances without sampling was evaluated. In order to realize the highly accurate rapid measurement, locally weighted partial least-squares (LW-PLS) with a new weighting technique was developed. LW-PLS is an adaptive method that builds a calibration model on demand by using a database whenever prediction is required. By adding more weight to samples closer to a query, LW-PLS can achieve higher prediction accuracy than PLS. In this study, a new weighting technique is proposed to further improve the prediction accuracy of LW-PLS. The root-mean-square error of prediction (RMSEP) of the IR-RAS spectra analyzed by LW-PLS with the new weighting technique was compared with that analyzed by PLS and locally weighted regression (LWR). The RMSEP of LW-PLS with the proposed weighting technique was about 36% and 14% smaller than that of PLS and LWR, respectively, when ibuprofen was a residual drug substance. Similarly, LW-PLS with the weighting technique was about 39% and 24% better than PLS and LWR in RMSEP, respectively, when magnesium stearate was a residual excipient. The combination of IR-RAS and LW-PLS with the proposed weighting technique is a very useful rapid measurement technique of the residual drug substances.

  4. Adaptive Liquid Crystal Windows

    SciTech Connect

    Taheri, Bahman; Bodnar, Volodymyr

    2011-12-31

    Energy consumption by private and commercial sectors in the U.S. has steadily grown over the last decade. The uncertainty in future availability of imported oil, on which the energy consumption relies strongly, resulted in a dramatic increase in the cost of energy. About 20% of this consumption are used to heat and cool houses and commercial buildings. To reduce dependence on the foreign oil and cut down emission of greenhouse gases, it is necessary to eliminate losses and reduce total energy consumption by buildings. To achieve this goal it is necessary to redefine the role of the conventional windows. At a minimum, windows should stop being a source for energy loss. Ideally, windows should become a source of energy, providing net gain to reduce energy used to heat and cool homes. It is possible to have a net energy gain from a window if its light transmission can be dynamically altered, ideally electronically without the need of operator assistance, providing optimal control of the solar gain that varies with season and climate in the U.S. In addition, the window must not require power from the building for operation. Resolution of this problem is a societal challenge and of national interest and will have a broad global impact. For this purpose, the year-round, allclimate window solution to provide an electronically variable solar heat gain coefficient (SHGC) with a wide dynamic range is needed. AlphaMicron, Inc. (AMI) developed and manufactured 1ft × 1ft prototype panels for the world’s first auto-adjusting Adaptive Liquid Crystal Windows (ALCWs) that can operate from sunlight without the need for external power source and demonstrate an electronically adjustable SHGC. This novel windows are based on AlphaMicron’s patented e-Tint® technology, a guesthost liquid crystal system implemented on flexible, optically clear plastic films. This technology is suitable both for OEM and aftermarket (retro-fitting) lamination to new and existing windows. Low level of

  5. Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.

    PubMed

    Arakawa, Hiroshi; Kamioka, Hiroki; Kanagawa, Masahiko; Hatano, Yasuko; Idota, Yoko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction.

  6. Calcium fluoride window mounting

    NASA Astrophysics Data System (ADS)

    Berger, D. Douglas

    1982-10-01

    A technique has been developed for joining a large calcium fluoride crystal to a stainless-steel flange by means of a silver transition ring. The process involves both vacuum brazing using a copper-silver alloy and air brazing using silver chloride. This paper describes the procedure used in fabricating a high-vacuum leak-tight calcium fluoride window assembly.

  7. Superconductive radiofrequency window assembly

    DOEpatents

    Phillips, Harry Lawrence; Elliott, Thomas S.

    1998-01-01

    The present invention is a superconducting radiofrequency window assembly for use in an electron beam accelerator. The srf window assembly (20) has a superconducting metal-ceramic design. The srf window assembly (20) comprises a superconducting frame (30), a ceramic plate (40) having a superconducting metallized area, and a superconducting eyelet (50) for sealing plate (40) into frame (30). The plate (40) is brazed to eyelet (50) which is then electron beam welded to frame (30). A method for providing a ceramic object mounted in a metal member to withstand cryogenic temperatures is also provided. The method involves a new metallization process for coating a selected area of a ceramic object with a thin film of a superconducting material. Finally, a method for assembling an electron beam accelerator cavity utilizing the srf window assembly is provided. The procedure is carried out within an ultra clean room to minimize exposure to particulates which adversely affect the performance of the cavity within the electron beam accelerator.

  8. Superconducting radiofrequency window assembly

    DOEpatents

    Phillips, Harry L.; Elliott, Thomas S.

    1997-01-01

    The present invention is a superconducting radiofrequency window assembly for use in an electron beam accelerator. The srf window assembly (20) has a superconducting metal-ceramic design. The srf window assembly (20) comprises a superconducting frame (30), a ceramic plate (40) having a superconducting metallized area, and a superconducting eyelet (50) for sealing plate (40) into frame (30). The plate (40) is brazed to eyelet (50) which is then electron beam welded to frame (30). A method for providing a ceramic object mounted in a metal member to withstand cryogenic temperatures is also provided. The method involves a new metallization process for coating a selected area of a ceramic object with a thin film of a superconducting material. Finally, a method for assembling an electron beam accelerator cavity utilizing the srf window assembly is provided. The procedure is carried out within an ultra clean room to minimize exposure to particulates which adversely affect the performance of the cavity within the electron beam accelerator.

  9. Windows and lighting program

    SciTech Connect

    Not Available

    1990-06-01

    More than 30% of all energy use in buildings is attributable to two sources: windows and lighting. Together they account for annual consumer energy expenditures of more than $50 billion. Each affects not only energy use by other major building systems, but also comfort and productivity -- factors that influence building economics far more than does direct energy consumption alone. Windows play a unique role in the building envelope, physically separating the conditioned space from the world outside without sacrificing vital visual contact. Throughout the indoor environment, lighting systems facilitate a variety of tasks associated with a wide range of visual requirements while defining the luminous qualities of the indoor environment. Windows and lighting are thus essential components of any comprehensive building science program. Despite important achievements in reducing building energy consumption over the past decade, significant additional savings are still possible. These will come from two complementary strategies: (1) improve building designs so that they effectively apply existing technologies and extend the market penetration of these technologies; and (2) develop advanced technologies that increase the savings potential of each application. Both the Windows and Daylighting Group and the Lighting System Research Group have made substantial contributions in each of these areas, and continue to do so through the ongoing research summarized here. 23 refs., 16 figs.

  10. Microwave Workshop for Windows.

    ERIC Educational Resources Information Center

    White, Colin

    1998-01-01

    "Microwave Workshop for Windows" consists of three programs that act as teaching aid and provide a circuit design utility within the field of microwave engineering. The first program is a computer representation of a graphical design tool; the second is an accurate visual and analytical representation of a microwave test bench; the third…

  11. "Stained Glass" Landscape Windows

    ERIC Educational Resources Information Center

    Vannata, Janine

    2008-01-01

    Both adults and children alike marvel at the grand vivid stained-glass windows created by American artist Louis Comfort Tiffany. Today he is commonly recognized as one of America's most influential designers and artists throughout the last nineteenth and early twentieth century. In the lesson described in this article, students created their own…

  12. Candles in Our Windows

    ERIC Educational Resources Information Center

    McGrath, Kathryn

    2005-01-01

    "Candles in Our Windows"--also titled "Nightlights"--is a play developed for elementary and middle school students about how residents in Billings, Montana, took a stand against hate. Last March, the 6th-grade students of Woodland Elementary School in New Jersey performed an early version of the play based on a children's book,…

  13. Exploring Shop Window Displays

    ERIC Educational Resources Information Center

    Christopoulou, Martha

    2011-01-01

    Using visual resources from everyday life in art lessons can enrich students' knowledge about the creation of visual images, artifacts, and sites, and develop their critical understanding about the cultural impact of these images and their effects on people's lives. Through examining an exhibition in the windows of Selfridges department store in…

  14. Windows to Art Excitement.

    ERIC Educational Resources Information Center

    Laird, Shirley; Crumpecker, Cheryl

    2003-01-01

    Describes an art project that aimed to bring more attention to an art program. Explains that the students created themed murals on the windows of the art classroom, such as a "Jungle,""Ocean,""Masterpiece Paintings," and "Rainforest Tree Frogs." Discusses how the murals were created. (CMK)

  15. Opening the Literature Window

    ERIC Educational Resources Information Center

    Jago, Carol

    2012-01-01

    Great literature gives students a window to other places and times, but it often requires students to step outside their comfort zones and take on challenges they wouldn't usually attempt. Unfortunately, research shows that many schools are not assigning literature that pushes students beyond their current reading level. Jago encourages teachers…

  16. Foamglass solar window collector

    NASA Astrophysics Data System (ADS)

    Grande, P. C.

    Solar heating of a living area by means of a foamglass window collector is reported. The collector was built with readily available materials available at most local hardware stores. The payback period was found to be 3.7 years, slightly longer than anticipated.

  17. Windows into Art Classrooms.

    ERIC Educational Resources Information Center

    Grauer, Kit, Ed.

    1995-01-01

    An editorial by Kit Grauer introduces this collection of articles which establish that there is no such thing as a simple definition of art education even within one culture, and that people's views can be reflected by art educators across the world. The first article, "A Window on Three Singapore Art Classrooms" (Jane Chia; John…

  18. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

    PubMed

    Drexel, Heinz

    2009-12-01

    Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.

  19. Study of noise transmission through double wall aircraft windows

    NASA Technical Reports Server (NTRS)

    Vaicaitis, R.

    1983-01-01

    Analytical and experimental procedures were used to predict the noise transmitted through double wall windows into the cabin of a twin-engine G/A aircraft. The analytical model was applied to optimize cabin noise through parametric variation of the structural and acoustic parameters. The parametric study includes mass addition, increase in plexiglass thickness, decrease in window size, increase in window cavity depth, depressurization of the space between the two window plates, replacement of the air cavity with a transparent viscoelastic material, change in stiffness of the plexiglass material, and different absorptive materials for the interior walls of the cabin. It was found that increasing the exterior plexiglass thickness and/or decreasing the total window size could achieve the proper amount of noise reduction for this aircraft. The total added weight to the aircraft is then about 25 lbs.

  20. Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

    PubMed Central

    Zeng, Ni; Gao, Xiaoling; Hu, Quanyin; Song, Qingxiang; Xia, Huimin; Liu, Zhongyang; Gu, Guangzhi; Jiang, Mengyin; Pang, Zhiqing; Chen, Hongzhuan; Chen, Jun; Fang, Liang

    2012-01-01

    Background Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized. Methods In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a “ ball-like”/“hexagonal” morphology. Results Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and to fuse with the cell membrane. An in vivo pharmacokinetic study showed that the oral bioavailability of paclitaxel-loaded LCNPs (13.16%) was 2.1 times that of Taxol® (the commercial formulation of paclitaxel, 6.39%). Conclusion The findings of this study suggest that this LCNP delivery system may be a promising candidate for improving the oral bioavailability of poorly water-soluble agents. PMID:22888230

  1. [Mucus models for investigation of intestinal absorption mechanisms. 3. A mathematical simulation model of drug diffusion through enteral mucus].

    PubMed

    Fahr, A; Guitard, P; Matthes, I; Nimmerfall, F; Nüesch, E; Sucker, H

    1992-09-01

    The diffusion of drug substance in a closed three-compartment model through a mucus layer to equilibrium is simulated by available pharmacokinetic programs. The obtained curves conform very well to the values experimentally found. If mucus is replaced by buffer solution an explicit equation from the literature, the method used and the experimental findings give the same results. Examination of the rate constants k1 for the diffusion in, kD through and k2 from the mucus shows the significance of the relation k1/k2 > 1, = 1, < 1 as a measure for the affinity of the active agent to the mucus. The discussion of the kinetic parameters shows, as in previous results, no criterion for assuming specific mucus binding. Because of its unspecifity the usual term "mucus binding" should be replaced by "mucus retention".

  2. VIEW OF THREE NORTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THREE NORTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ARE LOCATED JUST BELOW THE CHOIR LOFT. - U.S. Naval Base, Pearl Harbor, Chapel, Corner of Oakley & Nimitz Street, Pearl City, Honolulu County, HI

  3. VIEW OF THREE SOUTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THREE SOUTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ARE LOCATED ADJACENT TO THE ALTER. - U.S. Naval Base, Pearl Harbor, Chapel, Corner of Oakley & Nimitz Street, Pearl City, Honolulu County, HI

  4. VIEW OF THREE NORTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THREE NORTH FACING STAINED GLASS WINDOWS. THESE WINDOWS ARE LOCATED ADJACENT TO THE ALTAR. - U.S. Naval Base, Pearl Harbor, Chapel, Corner of Oakley & Nimitz Street, Pearl City, Honolulu County, HI

  5. details: window jamb from first period of construction; window jamb, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    details: window jamb from first period of construction; window jamb, sill profile, and transom profile from second period of construction - Joseph Poffenberger Farm, House, 17834 Mansfield Avenue, Sharpsburg, Washington County, MD

  6. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  7. Optimized ECR plasma apparatus with varied microwave window thickness

    DOEpatents

    Berry, Lee A.

    1995-01-01

    The present invention describes a technique to control the radial profile of microwave power in an ECR plasma discharge. In order to provide for a uniform plasma density to a specimen, uniform energy absorption by the plasma is desired. By controlling the radial profile of the microwave power transmitted through the microwave window of a reactor, the profile of the transmitted energy to the plasma can be controlled in order to have uniform energy absorption by the plasma. An advantage of controlling the profile using the window transmission characteristics is that variations to the radial profile of microwave power can be made without changing the microwave coupler or reactor design.

  8. Optimized ECR plasma apparatus with varied microwave window thickness

    DOEpatents

    Berry, L.A.

    1995-11-14

    The present invention describes a technique to control the radial profile of microwave power in an ECR plasma discharge. In order to provide for a uniform plasma density to a specimen, uniform energy absorption by the plasma is desired. By controlling the radial profile of the microwave power transmitted through the microwave window of a reactor, the profile of the transmitted energy to the plasma can be controlled in order to have uniform energy absorption by the plasma. An advantage of controlling the profile using the window transmission characteristics is that variations to the radial profile of microwave power can be made without changing the microwave coupler or reactor design. 9 figs.

  9. Constraints on relaxion windows

    NASA Astrophysics Data System (ADS)

    Choi, Kiwoon; Im, Sang Hui

    2016-12-01

    We examine the low energy phenomenology of the relaxion solution to the weak scale hierarchy problem. Assuming that the Hubble friction is responsible for a dissipation of the relaxion energy, we identify the cosmological relaxion window which corresponds to the parameter region compatible with a given value of the acceptable number of inflationary e-foldings. We then discuss a variety of observational constraints on the relaxion window, including those from astrophysical and cosmological considerations. We find that majority of the parameter space with a relaxion mass m ϕ ≳ 100 eV or a relaxion decay constant f ≲107GeV is excluded by existing constraints. There is an interesting parameter region with m ϕ ˜ 0 .2 - 10 GeV and f ˜ few - 200 TeV, which is allowed by existing constraints, but can be probed soon by future beam dump experiments such as the SHiP experiment, or by improved EDM experiments.

  10. Target Window Reliability

    SciTech Connect

    Woloshun, Keith Albert

    2016-02-11

    The target window design implemented and tested in experiments at ANL have performed without failure for the available beam of 6 mm FWHM on a 12 mm diameter target. However, scaling that design to a 25 mm diameter target size for a 12 mm FWHM beam has proven problematic. Combined thermal and mechanical (pressure induced) stresses and strains are too high to maintain the small coolant gaps and provide adequate fatigue lifetime.

  11. Daylight Redirecting Window Films

    DTIC Science & Technology

    2013-09-01

    photocontrols. The savings can range from 0.39 – 2.11 kWh/sf of the floor area based on the building location and window orientation. B. Photocontrols are...diffuser characteristics were carefully chosen to have no discernible impact on the optical characteristics of the system.1 F. The increase in... impact on glare. Since glare calculations and measurements are extremely difficult and fraught with errors, any glare assessment must be verified

  12. Lens window simplifies TDL housing

    NASA Technical Reports Server (NTRS)

    Robinson, D. M.; Rowland, C. W.

    1979-01-01

    Lens window seal in tunable-diode-laser housing replaces plan parallel window. Lens seals housing and acts as optical-output coupler, thus eliminating need for additional reimaging or collimating optics.

  13. Windows: The Benefits Are Clear.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    1999-01-01

    Discusses the importance of specifying windows in a school renovation or building project in order to energize a campus. Explains how windows are psychologically uplifting, how glass accentuates excitement and its shapes signal stability, and how windows convey the institution's confidence in the present. (GR)

  14. A Window-Washing Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    Skyscrapers sure do have a lot of windows, and these windows are cleaned and checked regularly. All this takes time, money, and puts workers at potential risk. Might there be a better way to do it? In this article, the author discusses a window-washing challenge and describes how students can tackle this task, pick up the challenge, and creatively…

  15. Windows Memory Forensic Data Visualization

    DTIC Science & Technology

    2014-06-12

    WINDOWS MEMORY FORENSIC DATA VISUALIZATION THESIS J. Brendan Baum, Civilian, USAF AFIT...WINDOWS MEMORY FORENSIC DATA VISUALIZATION THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School of...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED AFIT-ENG-T-14-J-1 WINDOWS MEMORY FORENSIC DATA VISUALIZATION J. Brendan Baum, B.S

  16. PAMPA--a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones.

    PubMed

    Bermejo, Marival; Avdeef, Alex; Ruiz, Ana; Nalda, Ricardo; Ruell, Jeffrey A; Tsinman, Oksana; González, Isabel; Fernández, Carlos; Sánchez, Gloria; Garrigues, Teresa M; Merino, Virginia

    2004-03-01

    Parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 4 to 10, of 17 fluoroquinolones, including three congeneric series with systematically varied alkyl chain length at the 4'N-position of the piperazine residue. The permeability values spanned over three orders of magnitude. The intrinsic permeability, P(o), and the membrane permeability, P(m), were determined from the pH dependence of the effective permeability. The pK(a) values were determined potentiometrically. The PAMPA method employed stirring, adjusted such that the unstirred water layer (UWL) thickness matched the 30-100 microm range estimated to be in the human small intestine. The intrinsic permeability coefficients (10(-6)cm/s), representing the permeability of the uncharged form of the drug, are for 4'N-R-norfloxacin: 0.7 (R=H), 49 (Me), 132 (n-Pr), 365 (n-Bu); 4'N-R-ciprofloxacin: 2.7 (H), 37 (Me), 137 (n-Pr), 302 (n-Bu); 4'N-R-3'-methylciprofloxacin: 3.8 (H), 20 (Me), 51 (Et), 160 (n-Pr), 418 (n-Bu). Increasing the alkyl chain length in the congeneric series resulted in increased permeability, averaging about 0.34 log units per methylene group, except that of the first (H-to-Me), which was about 1.2 log units. These results were compared to Caco-2 and rat in situ permeability measurements. The in situ closed loop technique used for obtaining permeability values in rat showed a water layer thickness effect quite consistent with in vivo expectations. The rat-PAMPA correlation (r2=0.87) was better than that of rat-Caco-2 (r2=0.63). Caco-2-PAMPA correlation indicated r2=0.66. The latter correlation improved significantly (r2=0.82) when the Caco-2 data were corrected for the UWL effect.

  17. Feasibility study of a cryogenically cooled window for high-power gyrotrons

    SciTech Connect

    Haste, G.R.; Kimrey, H.D.; Prosise, J.D.

    1986-07-01

    Single-crystal sapphire is currently in use as the material for output windows in high-power microwave tubes, particularly gyrotrons. These windows are currently being cooled by fluorocarbon fluids at near-room temperatures. There are, however, several advantages in operating the window at very low temperatures: less absorption and consequent heating of the window, greater material strength, improved resistance to crack formation, greater thermal conductivity, and reduced thermal expansion. Operation at cryogenic temperatures is shown to be feasible. The output power, which is currently limited by window constraints, could be increased by an order of magnitude or more.

  18. Window performance in extreme cold

    NASA Astrophysics Data System (ADS)

    Flanders, S. N.; Buska, J. S.; Barrett, S. A.

    1982-12-01

    Extreme cold causes heavy buildup of frost, ice and condensation on many windows. It also increases the incentive for improving the airtightness of windows against heat loss. Our study shows that tightening specifications for Alaskan windows to permit only 30% of the air leakage allowed by current American airtightness standards is economically attractive. We also recommend triple glazing in much of Alaska to avoid window icing in homes and barracks. We base our conclusions on a two year field study of Alaskan military bases that included recording humidity and temperature data, observing moisture accumulation on windows and measuring airtightness with a fan pressurized device.

  19. Sunlight Responsive Thermochromic Window System

    SciTech Connect

    Millett, F,A; Byker,H, J

    2006-10-27

    Pleotint has embarked on a novel approach with our Sunlight Responsive Thermochromic, SRT™, windows. We are integrating dynamic sunlight control, high insulation values and low solar heat gain together in a high performance window. The Pleotint SRT window is dynamic because it reversibly changes light transmission based on thermochromics activated directly by the heating effect of sunlight. We can achieve a window package with low solar heat gain coefficient (SHGC), a low U value and high insulation. At the same time our windows provide good daylighting. Our innovative window design offers architects and building designers the opportunity to choose their desired energy performance, excellent sound reduction, external pane can be self-cleaning, or a resistance to wind load, blasts, bullets or hurricanes. SRT windows would provide energy savings that are estimated at up to 30% over traditional window systems. Glass fabricators will be able to use existing equipment to make the SRT window while adding value and flexibility to the basic design. Glazing installers will have the ability to fit the windows with traditional methods without wires, power supplies and controllers. SRT windows can be retrofit into existing buildings,

  20. Cell culture models of the human cornea - a comparative evaluation of their usefulness to determine ocular drug absorption in-vitro.

    PubMed

    Reichl, Stephan

    2008-03-01

    Cell culture models of the cornea are continually developed to replace the isolated animal cornea for transcorneal drug absorption studies. The aim of this study was to determine and compare epithelial tightness and permeability of currently available corneal cell culture models to avoid interlaboratory variability and to assess their usefulness for in-vitro permeation studies. Pure epithelial cell culture models (CEPI, SIRC and HCE-T cell lines), primary cultures of human corneal epithelium (HCEpiC) and the two commercially available models (RHC and Epiocular), as well as organotypic human cornea constructs (HCC, HCC-HCE-T), were investigated and data were compared with those obtained from the excised bovine cornea. Barrier properties were assessed by measurements of transepithelial electrical resistance (TEER) and permeability of three passively absorbed substances (mannitol, testosterone and timolol maleate) with different physico-chemical properties. TEER experiments revealed weak barrier functions for all of the investigated epithelial models (

  1. X-ray absorption spectroscopy of an investigational anticancer gallium(III) drug: interaction with serum proteins, elemental distribution pattern, and coordination of the compound in tissue.

    PubMed

    Hummer, Alfred A; Bartel, Caroline; Arion, Vladimir B; Jakupec, Michael A; Meyer-Klaucke, Wolfram; Geraki, Tina; Quinn, Paul D; Mijovilovich, Ana; Keppler, Bernhard K; Rompel, Annette

    2012-06-14

    Tris(8-quinolinolato)gallium(III) (1, KP46) is a very promising investigational anticancer drug. Its interaction with serum proteins, elemental distribution, and coordination in tissue were investigated with X-ray absorption (XAS) methods. Model compounds with mixed O, N, and/or S donor atoms are reported. The coordination and structure of 1 in cell culture medium (minimum essential medium, MEM) and fetal calf serum (FCS) were probed by XANES and EXAFS. The interaction of 1 with the serum proteins apotransferrin (apoTf) and human serum albumin (HSA) was addressed as well. By application of micro-XAS to tissue samples from mice treated with 1, the gallium distribution pattern was analyzed and compared to those of physiological trace elements. The complex 1 turned out to be very stable under physiological conditions, in cell culture media and in tissue samples. The coordination environment of the metal center remains intact in the presence of apoTf and HSA. The gallium distribution pattern in tumor and liver tissue revealed high similarities to the distribution patterns of Zn and Fe, minor similarities to Cu and Ni, and no similarity to Ca.

  2. Implementing Audio-CASI on Windows' Platforms.

    PubMed

    Cooley, Philip C; Turner, Charles F

    1998-01-01

    Audio computer-assisted self interviewing (Audio-CASI) technologies have recently been shown to provide important and sometimes dramatic improvements in the quality of survey measurements. This is particularly true for measurements requiring respondents to divulge highly sensitive information such as their sexual, drug use, or other sensitive behaviors. However, DOS-based Audio-CASI systems that were designed and adopted in the early 1990s have important limitations. Most salient is the poor control they provide for manipulating the video presentation of survey questions. This article reports our experiences adapting Audio-CASI to Microsoft Windows 3.1 and Windows 95 platforms. Overall, our Windows-based system provided the desired control over video presentation and afforded other advantages including compatibility with a much wider array of audio devices than our DOS-based Audio-CASI technologies. These advantages came at the cost of increased system requirements --including the need for both more RAM and larger hard disks. While these costs will be an issue for organizations converting large inventories of PCS to Windows Audio-CASI today, this will not be a serious constraint for organizations and individuals with small inventories of machines to upgrade or those purchasing new machines today.

  3. Windows on the axion

    SciTech Connect

    Turner, M.S.

    1989-04-01

    Peccei-Quinn symmetry with attendant axion is a most compelling, and perhaps the most minimal, extension of the standard model, as it provides a very elegant solution to the nagging strong CP-problem associated with the THETA vacuum structure of QCD. However, particle physics gives little guidance as to the axion mass; a priori, the plausible values span the range: 10/sup /minus/12/ eV /approx lt/ m/sub a/ /approx lt/ 10/sup 6/ eV, some 18 orders-of-magnitude. Axions have a host of interesting astrophysical and cosmological effects, including, modifying the evolution of stars of all types (our sun, red giants, white dwarfs, and neutron stars), contributing significantly to the mass density of the Universe today, and producing detectable line radiation through the decays of relic axions. Consideration of these effects has probed 14 orders-of-magnitude in axion mass, and has left open only two windows for further exploration: 10/sup /minus/6/ eV /approx lt/ m/sub a/ /approx lt/ 10/sup /minus/3/ eV and 1 eV /approx lt/ m/sub a/ /approx lt/ 5 eV (hadronic axions only). Both these windows are accessible to experiment, and a variety of very interesting experiments, all of which involve ''heavenly axions,'' are being planned or are underway. 58 refs., 6 figs., 1 tab.

  4. [Rat intestinal absorption trait of peimine and peiminine in Thunberg fritillary bulb extract].

    PubMed

    Guan, Zhi-Yu; Zhang, Li-Hua; Chen, Li-Hua; Zhu, Wei-Feng; Liu, Hong-Ning

    2013-12-01

    To study the in situ intestinal absorption kinetics and compatibility influence of peimine and peiminine in rats, the absorption of peimine and peiminine in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct ligation can significantly affect the absorption of peimine and peiminine, the Ka, and Papp values in the condition of pH 6.8 and pH 7.4 had significant difference (P<0.01), as drug concentration irlcreased, the absorption parameters of peimine and peiminine decreased, Ka and Papp between low concentrations and middle concentrations was significant difference (P<0.01). Verapamil can not affect Ka and Papp of peimine and peiminine which are in the extract (P> 0.05). Bitter almonds and licorice can significantly reduce the absorption of peimine and peiminine with the usual dose (P<0.01), extracted separately and together had no significant difference on Ka and Papp (P> 0.05). Experimental results show that the absorption features of peimine and peiminine are basically the same, both of them could be absorbed at all segments of the intestine in rats and had no special absorption window, and with significant differences between male and female individuals. The absorption of peimine and peiminine complies with the active transport and facilitated diffusion in the general intestinal segments. Bitter almond and licorice can reduce the intestinal absorption rate ofpeimine and peiminine.

  5. Switchable Solar Window Devices Based on Polymer Dispersed Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Murray, Joseph; Ma, Dakang; Munday, Jeremy

    Windows are an interesting target for photovoltaics due to the potential for large area of deployment and because glass is already a ubiquitous component of solar cell devices. Many demonstrations of solar windows in recent years have used photovoltaic devices which are semitransparent in the visible region. Much research has focused on enhancing device absorption in the UV and IR ranges as a means to circumvent the basic tradeoff between efficiency and transparency to visible light. Use of switchable solar window is a less investigated alternative approach; these windows utilize the visible spectrum but can toggle between high transparency and high efficiency as needed. We present a novel switchable solar window device based on Polymer Dispersed Liquid Crystals (PDLC). By applying an electric field to the PDLC layer, the device can be switched from an opaque, light diffusing, efficient photovoltaic cell to a clear, transparent window. In the off state (i.e. scattering state), these devices have the added benefits of increased reflectivity for reduced lighting and cooling costs and haze for privacy. Further, we demonstrate that these windows have the potential for self-powering due to the very low power required to maintain the on, or high transparency, state. Support From: University of Maryland and Maryland Nano-center and its Fablab.

  6. Optimisation of sampling windows design for population pharmacokinetic experiments.

    PubMed

    Ogungbenro, Kayode; Aarons, Leon

    2008-08-01

    This paper describes an approach for optimising sampling windows for population pharmacokinetic experiments. Sampling windows designs are more practical in late phase drug development where patients are enrolled in many centres and in out-patient clinic settings. Collection of samples under the uncontrolled environment at these centres at fixed times may be problematic and can result in uninformative data. Population pharmacokinetic sampling windows design provides an opportunity to control when samples are collected by allowing some flexibility and yet provide satisfactory parameter estimation. This approach uses information obtained from previous experiments about the model and parameter estimates to optimise sampling windows for population pharmacokinetic experiments within a space of admissible sampling windows sequences. The optimisation is based on a continuous design and in addition to sampling windows the structure of the population design in terms of the proportion of subjects in elementary designs, number of elementary designs in the population design and number of sampling windows per elementary design is also optimised. The results obtained showed that optimal sampling windows designs obtained using this approach are very efficient for estimating population PK parameters and provide greater flexibility in terms of when samples are collected. The results obtained also showed that the generalized equivalence theorem holds for this approach.

  7. Window defect planar mapping technique

    NASA Technical Reports Server (NTRS)

    Minton, F. R.; Minton, U. O. (Inventor)

    1976-01-01

    A method of planar mapping defects in a window having an edge surface and a planar surface. The method is comprised of steps for mounting the window on a support surface. Then a light sensitive paper is placed adjacent to the window surface. A light source is positioned adjacent to the window edge. The window is then illuminated with the source of light for a predetermined interval of time. Defects on the surface of the glass, as well as in the interior of the glass are detected by analyzing the developed light sensitive paper. The light source must be in the form of optical fibers or a light tube whose light transmitting ends are placed near the edge surface of the window.

  8. Absorption Coefficient of Alkaline Earth Halides.

    DTIC Science & Technology

    1980-04-01

    levels . As a natural consequence, the magnitude of the absorption coefficient is the key parameter in selecting laser window materials. Over the past...of as can be achieved through improved crystal growing techniques and surface polishing. 2.5. Urbach’s Rule A central question for the development of...high absorption levels , inaccuracies progressively increasing with decreasing absorption level , a natural consequence of decreasing in instrumental

  9. Redefining the Axion Window

    NASA Astrophysics Data System (ADS)

    Di Luzio, Luca; Mescia, Federico; Nardi, Enrico

    2017-01-01

    A major goal of axion searches is to reach inside the parameter space region of realistic axion models. Currently, the boundaries of this region depend on somewhat arbitrary criteria, and it would be desirable to specify them in terms of precise phenomenological requirements. We consider hadronic axion models and classify the representations RQ of the new heavy quarks Q . By requiring that (i) the Q 's are sufficiently short lived to avoid issues with long-lived strongly interacting relics, (ii) no Landau poles are induced below the Planck scale; 15 cases are selected which define a phenomenologically preferred axion window bounded by a maximum (minimum) value of the axion-photon coupling about 2 times (4 times) larger than is commonly assumed. Allowing for more than one RQ, larger couplings, as well as complete axion-photon decoupling, become possible.

  10. Subject Responses to Electrochromic Windows

    SciTech Connect

    Clear, Robert; Inkarojrit, Vorapat; Lee, Eleanor

    2006-03-03

    Forty-three subjects worked in a private office with switchable electrochromic windows, manually-operated Venetian blinds, and dimmable fluorescent lights. The electrochromic window had a visible transmittance range of approximately 3-60%. Analysis of subject responses and physical data collected during the work sessions showed that the electrochromic windows reduced the incidence of glare compared to working under a fixed transmittance (60%) condition. Subjects used the Venetian blinds less often and preferred the variable transmittance condition, but used slightly more electric lighting with it than they did when window transmittance was fixed.

  11. Window Observational Research Facility (WORF)

    NASA Technical Reports Server (NTRS)

    Pelfrey, Joseph; Sledd, Annette

    2007-01-01

    This viewgraph document concerns the Window Observational Research Facility (WORF) Rack, a unique facility designed for use with the US Lab Destiny Module window. WORF will provide valuable resources for Earth Science payloads along with serving the purpose of protecting the lab window. The facility can be used for remote sensing instrumentation test and validation in a shirt sleeve environment. WORF will also provide a training platform for crewmembers to do orbital observations of other planetary bodies. WORF payloads will be able to conduct terrestrial studies utilizing the data collected from utilizing WORF and the lab window.

  12. Ecophysiological function of leaf 'windows' in Lithops species - 'Living Stones' that grow underground.

    PubMed

    Martin, C E; Brandmeyer, E A; Ross, R D

    2013-01-01

    Leaf temperatures were lower when light entry at the leaf tip window was prevented through covering the window with reflective tape, relative to leaf temperatures of plants with leaf tip windows covered with transparent tape. This was true when leaf temperatures were measured with an infrared thermometer, but not with a fine-wire thermocouple. Leaf tip windows of Lithops growing in high-rainfall regions of southern Africa were larger than the windows of plants (numerous individuals of 17 species) growing in areas with less rainfall and, thus, more annual insolation. The results of this study indicate that leaf tip windows of desert plants with an underground growth habit can allow entry of supra-optimal levels of radiant energy, thus most likely inhibiting photosynthetic activity. Consequently, the size of the leaf tip windows correlates inversely with habitat solar irradiance, minimising the probability of photoinhibition, while maximising the absorption of irradiance in cloudy, high-rainfall regions.

  13. INTERIOR DETAIL, RETRACTABLE WINDOW SHUTTERS, VENETIAN WINDOW IN THE SOUTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    INTERIOR DETAIL, RETRACTABLE WINDOW SHUTTERS, VENETIAN WINDOW IN THE SOUTHEAST CABINET. (NOTE THE MIRRORED PANEL IN THE FORWARD SHUTTER’S LOWER SECTION. DURING THE HAMILTONIAN OCCUPANCY, MIRRORS LIKE THESE WERE USED LIBERALLY THROUGHOUT THE HOUSE’S PUBLIC ROOMS - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  14. What Becomes a Window Most: Perceptual Tuning of Virtual Windows

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Stone, Lee (Technical Monitor)

    1997-01-01

    Viewing a scene through an optical window provides observers with numerous visual properties. In order to create a 'virtual window' that is perceptually compelling, it must be determined which properties are most critical to preserve. We have examined several properties, both static and dynamic, and will discuss which have the greatest impact on apparent realism (and user performance).

  15. Study on the interactions of antiemetic drugs and 12-tungstophosphoric acid by absorption and resonance Rayleigh scattering spectra and their analytical applications.

    PubMed

    Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Hu, Xiaoli

    2013-03-15

    In 0.1 mol L(-1) HCl medium, antiemetic drugs (ATM), such as granisetron hydrochloride (GS) and tropisetron hydrochloride (TS), reacted with H(3)PW(12)O(40)·nH(2)O and formed 3:1 ion-association complex of [(ATM)(3)PW(12)O(40)], then self-aggregated into nanoparticles-[(ATM)(3)PW(12)O(40)](n) with an average size of 100 nm. The reaction resulted in the enhancement of resonance Rayleigh scattering (RRS) and the absorption spectra. The increments of scattering intensity (ΔI(RRS)) and the change of absorbance (ΔA) were both directly proportional to the concentrations of ATM in certain ranges. Accordingly, two new RRS and spectrophotometric methods were proposed for ATM detection. The detection limits (3σ) of GS and TS were 3.2 ng mL(-1) and 4.0 ng mL(-1)(RRS method), 112.5 ng mL(-1) and 100.0 ng mL(-1)(spectrophotometric method). These two methods were applied to determine GS in orally disintegrating tablets and the results were in good agreement with the official method. The ground-state geometries and electronic structures of GS and TS were optimized by the hybrid density functional theory (DFT) method and the shape of [(ATM)(3)PW(12)O(40)](n) was characterized by atomic force microscopy (AFM). Take the RRS method with higher sensitivity as an example, the reaction mechanism and the reasons for enhancement of scattering were discussed.

  16. Proximal Roux-en-Y Gastric Bypass Alters Drug Absorption Pattern But Not Systemic Exposure of CYP3A4 and P-glycoprotein Substrates

    PubMed Central

    Chan, Lingtak-Neander; Lin, Yvonne S.; Tay-Sontheimer, Jessica C.; Trawick, Dorothy; Oelschlager, Brant K.; Flum, David R.; Patton, Kristen K.; Shen, Danny D.; Horn, John R.

    2015-01-01

    Study Objectives To evaluate the effect of Roux-en-Y gastric bypass surgery (RYGB) on the pharmacokinetics of midazolam (a CYP3A4 substrate) and digoxin (a P-glycoprotein substrate). Design Prospective, nonblinded, longitudinal, single-dose pharmacokinetic study in three phases: presurgery baseline and postoperative assessments at 3 and 12 months. Patients Twelve obese patients meeting current standards for bariatric surgery. Measurements and Main Results At each study visit, patients received a single dose of oral digoxin and midazolam at 8 a.m. Blood samples were collected at regular intervals for 24 hours after dosing. Continuous 12-lead electrocardiogram (EKG), heart rate, blood pressure, and respiratory rate were monitored, and pharmacokinetic parameters from the three visits were compared. The peak plasma concentration (Cmax) of midazolam increased by 66% and 71% at 3- and 12-month post-RYGB (p=0.017 and p=0.001, respectively), whereas the median time to peak concentration (Tmax) was reduced by 50%. The mean Cmax for 1′-hydroxymidazolam increased by 87% and 80% at 3 and 12 months (p=0.001 and p<0.001, respectively). However, neither the area under the concentration-time curve (AUC) for midazolam nor the metabolite-to-parent AUC ratio changed significantly over time. For digoxin, the median Tmax decreased from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months, respectively. The mean AUC for digoxin, heart rate, and EKG patterns were similar across the three study phases. Conclusion Contemporary proximal RYGB increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin. The Cmax of a CYP3A4 substrate with a high extraction ratio was substantially increased after RYGB. PMID:25757445

  17. Chronotherapeutic oral drug absorption system verapamil is effective in reducing morning blood pressure in African Americans: a post hoc analysis of the chrono trial.

    PubMed

    Prisant, L Michael; Weber, Michael; Black, Henry R

    2005-03-01

    Results of several clinical trials have shown that verapamil is effective in reducing blood pressure (BP) in African Americans, a population at high risk for hypertension and target-organ damage. Nonetheless, adequate control of BP is perceived as difficult to achieve in this population. A post hoc analysis of data from the community-based CHRONO trial (Controlling Hypertension in the moRning with a ChrONO medication) was undertaken to assess racial/ethnic differences in the safety and efficacy of the Chronotherapeutic Oral Drug Absorption System (CODAS) formulation of verapamil in a real-world setting. Once-daily administration of the CODAS formulation of verapamil significantly reduced morning BP (P<0.0001) regardless of race or ethnicity. In the African-American population (N=466), the response rate for systolic BP (<140 mmHg or > or =10% reduction from baseline) and diastolic BP (<90 mmHg or reduction > or =10 mmHg from baseline) combined was 70.8%, and 60% of those individuals responded at the lowest (200 mg) dose. Of the 59.7% of African Americans who reached the target BP of <140/90 mmHg, 64% did so at the 200-mg dose. Response rates were not affected by gender, age or treatment history, and CODAS-verapamil was well tolerated in all ethnic/racial treatment groups. In a trial conducted in actual clinical practices, the CODAS formulation of verapamil was shown to be safe and effective in African Americans, Caucasians, Hispanics and Asians.

  18. Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers.

    PubMed

    Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil; Jacobsen, Jette; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette

    2016-03-10

    Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.

  19. Decades of research in drug targeting to the upper gastrointestinal tract using gastroretention technologies: where do we stand?

    PubMed

    Awasthi, Rajendra; Kulkarni, Giriraj T

    2016-01-01

    A major constraint in oral controlled release drug delivery is that not all the drug candidates are absorbed uniformly throughout the gastrointestinal tract (GIT). Drugs having "absorption window" are absorbed in a particular portion of GIT only or are absorbed to a different extent in various segments of the GIT. Thus, only the drug released in the region preceding and in close vicinity to the absorption window is available for absorption. The drug must be released from the dosage form in solution form; otherwise, it is generally not absorbed. Hence, much research has been dedicated to the development of gastroretentive drug delivery systems that may optimize the bioavailability and subsequent therapeutic efficacy of such drugs, as these systems have unique properties to bypass the gastric emptying process. These systems show excellent in vitro results but fail to give desirable in vivo performance. During the last 2-3 decades, researchers from the academia and industries are giving considerable importance in this field. Unfortunately, till date, few so-called gastroretentive dosage forms have been brought to the market in spite of numerous academic publications. The manuscript considers strategies that are commonly used in the development of gastroretentive drug delivery systems with a special attention on various parameters, which needs to be monitored during formulation development.

  20. Prism Window for Optical Alignment

    NASA Technical Reports Server (NTRS)

    Tang, Hong

    2008-01-01

    A prism window has been devised for use, with an autocollimator, in aligning optical components that are (1) required to be oriented parallel to each other and/or at a specified angle of incidence with respect to a common optical path and (2) mounted at different positions along the common optical path. The prism window can also be used to align a single optical component at a specified angle of incidence. Prism windows could be generally useful for orienting optical components in manufacture of optical instruments. "Prism window" denotes an application-specific unit comprising two beam-splitter windows that are bonded together at an angle chosen to obtain the specified angle of incidence.

  1. Window survivability in endoatmospheric environments

    NASA Astrophysics Data System (ADS)

    Lumb, Stewart B.; Majeski, Judith A.; Mills, J. S.

    1993-06-01

    An optical seeker window has been shown to survive hypersonic, endoatmospheric environments such as those encountered during Theater Defense or National Missile Defense engagements. The two periods most critical to the window are shroud removal and the subsequent cooling during acquisition and homing. The loads encountered during shroud removal are predicted by applying scaling functions to wind tunnel data. A nonlinear dynamic transient stress analysis is shown to match the wind tunnel strain measurements. The predicted stresses are then input into a Weibull statistical method to predict the probability of window survival during shroud separation. After the shroud is away, the window requires cooling to prevent excessive distortion caused by rapid heating. Analyses show that deflections of the window are small. The thermally induced stresses are low compared to stresses during shroud removal.

  2. Destiny's Earth Observation Window

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronaut Michael J. Bloomfield, STS-110 mission commander, looks through the Earth observation window in the Destiny laboratory aboard the International Space Station (ISS). The STS-110 mission prepared the ISS for future spacewalks by installing and outfitting the S0 (S-zero) truss and the Mobile Transporter. The 43-foot-long S0 Truss, weighing in at 27,000 pounds, was the first of 9 segments that will make up the Station's external framework that will eventually stretch 356 feet (109 meters), or approximately the length of a football field. This central truss segment also includes a flatcar called the Mobile Transporter and rails that will become the first 'space railroad,' which will allow the Station's robotic arm to travel up and down the finished truss for future assembly and maintenance. The completed truss structure will hold solar arrays and radiators to provide power and cooling for additional international research laboratories from Japan and Europe that will be attached to the Station. Milestones of the STS-110 mission included the first time the ISS robotic arm was used to maneuver spacewalkers around the Station and marked the first time all spacewalks were based out of the Station's Quest Airlock. It was also the first Shuttle to use three Block II Main Engines. The Space Shuttle Orbiter Atlantis, STS-110 mission, was launched April 8, 2002 and returned to Earth April 19, 2002.

  3. Tuning the chemosensory window

    PubMed Central

    Zhou, Shanshan; Mackay, Trudy FC

    2010-01-01

    Accurate perception of chemical signals from the environment is critical for the fitness of most animals. Drosophila melanogaster experiences its chemical environment through families of chemoreceptors that include olfactory receptors, gustatory receptors and odorant binding proteins. Its chemical environment, however, changes during its life cycle and the interpretation of chemical signals is dependent on dynamic social and physical surroundings. Phenotypic plasticity of gene expression of the chemoreceptor repertoire allows flies to adjust the chemosensory window through which they “view” their world and to modify the ensemble of expressed chemoreceptor proteins in line with their developmental and physiological state and according to their needs to locate food and oviposition sites under different social and physical environmental conditions. Furthermore, males and females differ in their expression profiles of chemoreceptor genes. Thus, each sex experiences its chemical environment via combinatorial activation of distinct chemoreceptor ensembles. The remarkable phenotypic plasticity of the chemoreceptor repertoire raises several fundamental questions. What are the mechanisms that translate environmental cues into regulation of chemoreceptor gene expression? How are gustatory and olfactory cues integrated perceptually? What is the relationship between ensembles of odorant binding proteins and odorant receptors? And, what is the significance of co-regulated chemoreceptor transcriptional networks? PMID:20305396

  4. Deep optical imaging of tissue using the second and third near-infrared spectral windows.

    PubMed

    Sordillo, Laura A; Pu, Yang; Pratavieira, Sebastião; Budansky, Yury; Alfano, Robert R

    2014-05-01

    Light at wavelengths in the near-infrared (NIR) region allows for deep penetration and minimal absorption through high scattering tissue media. NIR light has been conventionally used through the first NIR optical tissue window with wavelengths from 650 to 950 nm. Longer NIR wavelengths had been overlooked due to major water absorption peaks and a lack of NIR-CCD detectors. The second NIR spectral window from 1100 to 1350 nm and a new spectral window from 1600 to 1870 nm, known as the third NIR optical window, were investigated. Optical attenuation measurements from thin tissue slices of normal and malignant breast and prostate tissues, pig brain, and chicken tissue were obtained in the spectral range from 400 to 2500 nm. Optical images of chicken tissue overlying three black wires were also obtained using the second and third spectral windows. Due to a reduction in scattering and minimal absorption, longer attenuation lengths and clearer optical images could be seen in the second and third NIR optical windows compared to the conventional first NIR optical window. A possible fourth optical window centered at 2200 nm was noted.

  5. Tokamak physics experiment: Diagnostic windows study

    SciTech Connect

    Merrigan, M.; Wurden, G.A.

    1995-11-01

    We detail the study of diagnostic windows and window thermal stress remediation in the long-pulse, high-power Tokamak Physics Experiment (TPX) operation. The operating environment of the TPX diagnostic windows is reviewed, thermal loads on the windows estimated, and cooling requirements for the windows considered. Applicable window-cooling technology from other fields is reviewed and its application to the TPX windows considered. Methods for TPX window thermal conditioning are recommended, with some discussion of potential implementation problems provided. Recommendations for further research and development work to ensure performance of windows in the TPX system are presented.

  6. Analysis of the impact of controlled release formulations on oral drug absorption, gut wall metabolism and relative bioavailability of CYP3A substrates using a physiologically-based pharmacokinetic model.

    PubMed

    Olivares-Morales, Andrés; Kamiyama, Yoshiteru; Darwich, Adam S; Aarons, Leon; Rostami-Hodjegan, Amin

    2015-01-25

    Controlled release (CR) formulations are usually designed to achieve similar exposure (AUC) levels as the marketed immediate release (IR) formulation. However, the AUC is often lower following CR compared to IR formulations. There are a few exceptions when the CR formulations have shown higher AUC. This study investigated the impact of CR formulations on oral drug absorption and CYP3A4-mediated gut wall metabolism. A review of the current literature on relative bioavailability (Frel) between CR and IR formulations of CYP3A substrates was conducted. This was followed by a systematic analysis to assess the impact of the release characteristics and the drug-specific factors (including metabolism and permeability) on oral bioavailability employing a physiologically-based pharmacokinetic (PBPK) modelling and simulation approach. From the literature review, only three CYP3A4 substrates showed higher Frel when formulated as CR. Several scenarios were investigated using the PBPK approach; in most of them, the oral absorption of CR formulations was lower as compared to the IR formulations. However, for highly permeable compounds that were CYP3A4 substrates the reduction in absorption was compensated by an increase in the fraction that escapes from first pass metabolism in the gut wall (FG), where the magnitude was dependent on CYP3A4 affinity. The systematic simulations of various interplays between different parameters demonstrated that BCS class 1 highly-cleared CYP3A4 substrates can display up to 220% higher relative bioavailability when formulated as CR compared to IR, in agreement with the observed data collected from the literature. The results and methodology of this study can be employed during the formulation development process in order to optimize drug absorption, especially for CYP3A4 substrates.

  7. Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin.

    PubMed

    Martinez, Marilyn; Mistry, Bipin; Lukacova, Viera; Polli, Jim; Hoag, Stephen; Dowling, Thomas; Kona, Ravikanth; Fahmy, Raafat

    2016-07-01

    This study explored the utility of mechanistic absorption models to describe the in vivo performance of a low solubility/low permeability compound in normal healthy subjects. Sixteen healthy human volunteers received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by HPLC. In vitro ciprofloxacin release from the oral tablets was tested under a variety of conditions. A mechanistic model was used to explore in vivo dissolution and intestinal absorption. Although dissolution rate influenced the location of drug release, absorption challenges appeared to be associated with permeability limitations in the lower small intestine and colon. The apparent relationship between drug solubilization within the upper small intestinal and formulation overall bioavailability suggested the presence of an intestinal absorption window in many individuals. Failure to absorb drug within this window appeared to be linked with the likelihood of in vivo drug precipitation. Challenges encountered during this modeling exercise included large intersubject variability in product in vivo dissolution and the apparent limitations in ciprofloxacin absorption. Although transporter activity was not included as a model parameter, this evaluation demonstrated how identifying the location of drug absorption across several formulations provided an opportunity to identify factors to consider when formulating similar low solubility/low permeability compounds. The use of mechanistic models was invaluable for our understanding of in vivo product performance and for the assessment of individual profiles rather than means. The latter was essential for understanding the potential challenges that may be encountered when introducing a formulation into a patient population.

  8. Subgap Absorption in Conjugated Polymers

    DOE R&D Accomplishments Database

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of < 10{sup {minus}5}, Photothermal Deflection Spectroscopy (PDS) is ideal for determining the absorption coefficients of thin films of transparent'' materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  9. Window-closing safety system

    DOEpatents

    McEwan, Thomas E.

    1997-01-01

    A safety device includes a wire loop embedded in the glass of a passenger car window and routed near the closing leading-edge of the window. The wire loop carries microwave pulses around the loop to and from a transceiver with separate output and input ports. An evanescent field only and inch or two in radius is created along the wire loop by the pulses. Just about any object coming within the evanescent field will dramatically reduce the energy of the microwave pulses received back by the transceiver. Such a loss in energy is interpreted as a closing area blockage, and electrical interlocks are provided to halt or reverse a power window motor that is actively trying to close the window.

  10. Single Project Replaces District's Windows.

    ERIC Educational Resources Information Center

    American School and University, 1981

    1981-01-01

    The towns of Maplewood and South Orange (New Jersey) earmarked over $1 million, raised from a bond issue, to replace with thermal aluminum-framed units the 2400 worn out windows in eight 50-year-old schools. (Author)

  11. Window-closing safety system

    DOEpatents

    McEwan, T.E.

    1997-08-26

    A safety device includes a wire loop embedded in the glass of a passenger car window and routed near the closing leading-edge of the window. The wire loop carries microwave pulses around the loop to and from a transceiver with separate output and input ports. An evanescent field only an inch or two in radius is created along the wire loop by the pulses. Just about any object coming within the evanescent field will dramatically reduce the energy of the microwave pulses received back by the transceiver. Such a loss in energy is interpreted as a closing area blockage, and electrical interlocks are provided to halt or reverse a power window motor that is actively trying to close the window. 5 figs.

  12. A window on urban sustainability

    SciTech Connect

    Stigt, Rien van; Driessen, Peter P.J.; Spit, Tejo J.M.

    2013-09-15

    Sustainable urban development requires the integration of environmental interests in urban planning. Although various methods of environmental assessment have been developed, plan outcomes are often disappointing due to the complex nature of decision-making in urban planning, which takes place in multiple arenas within multiple policy networks involving diverse stakeholders. We argue that the concept of ‘decision windows’ can structure this seemingly chaotic chain of interrelated decisions. First, explicitly considering the dynamics of the decision-making process, we further conceptualized decision windows as moments in an intricate web of substantively connected deliberative processes where issues are reframed within a decision-making arena, and interests may be linked within and across arenas. Adopting this perspective in two case studies, we then explored how decision windows arise, which factors determine their effectiveness and how their occurrence can be influenced so as to arrive at more sustainable solutions. We conclude that the integration of environmental interests in urban planning is highly dependent on the ability of the professionals involved to recognize and manipulate decision windows. Finally, we explore how decision windows may be opened. -- Highlights: • Decision-making about sustainable urban development occurs in networks. • The concept of ‘decision windows’ was further elaborated. • Decision windows help understand how environmental interests enter decision-making. • Decision windows can, to some extent, be influenced.

  13. Assessing the absorption of new pharmaceuticals.

    PubMed

    Hidalgo, I J

    2001-11-01

    The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover 'loser' compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux-limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.

  14. Anomalous atmospheric absorption spectra due to water dimer

    NASA Astrophysics Data System (ADS)

    Cai, Peipei; Zhang, Hansheng; Shen, Shanxiong; Cheng, I.-Shan

    1986-11-01

    The anomalous atmospheric absorption spectra in the window wavelength region of 8-14 microns have been suggested due to the water dimer. Based on laboratory measurements, water continuum CO2 laser absorption spectra and a resonance absorption line due to the weak local wave vapor pure rotational transition have been reported. The equilibrium concentration of water dimers in the atmosphere, the electronic binding energy and the theoretical calculations for absorption attenuation have been obtained in agreement with published data.

  15. Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases.

    PubMed

    Babizhayev, Mark A

    2009-01-01

    lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and

  16. Spectral selectivity of electrochromic windows with color state for all-sky conditions

    SciTech Connect

    Soule, D E; Zhang, J G; Benson, D K

    1995-07-01

    The optical performance of an electrochromic window is studied for the visible, ultraviolet, and near infrared spectral regions. The performance is found to deviate strongly with window color state and for clear or cloudy skies. A new spectral cloud model is applied to an electrochromic window recently developed at NREL. A spectral comparison is made between the electrochromic window and spectrally selective standard windows. Two series of double-glazed window sections, including the electrochromic window with color state and a series of low-E windows, were measured for transmittance and reflectance (300-2500nm), With these spectral data, a new near-infrared blocking (reflection + absorption) factor is developed for window application in warm climates for cooling load reduction. A chromaticity analysis is presented for both the daylight spectra and the transmitted electrochromic window spectra with color state, Computed daylight correlated color temperatures show a wide range, with values of 5660K for clear global irradiation, 6210K for clouds, and 13,250K for a zenith blue sky. Chromatic trajectories with color state for transmitted radiation extend further toward the blue to 8180K for the global and 28,990K for zenith sky irradiation.

  17. Window decompression in laser-heated MagLIF targets

    NASA Astrophysics Data System (ADS)

    Woodbury, Daniel; Peterson, Kyle; Sefkow, Adam

    2015-11-01

    The Magnetized Liner Inertial Fusion (MagLIF) concept requires pre-magnetized fuel to be pre-heated with a laser before undergoing compression by a thick solid liner. Recent experiments and simulations suggest that yield has been limited to date by poor laser preheat and laser-induced mix in the fuel region. In order to assess laser energy transmission through the pressure-holding window, as well as resultant mix, we modeled window disassembly under different conditions using 1D and 2D simulations in both Helios and HYDRA. We present results tracking energy absorption, time needed for decompression, risk of laser-plasma interaction (LPI) that may scatter laser light, and potential for mix from various window thicknesses, laser spot sizes and gas fill densities. These results indicate that using thinner windows (0.5-1 μm windows) and relatively large laser spot radii (600 μm and above) can avoid deleterious effects and improve coupling with the fuel. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the National Nuclear Security Administration under DE-AC04- 94AL85000.

  18. Highlights From the American Association of Pharmaceutical Scientists/ International Transporter Consortium Joint Workshop on Drug Transporters in Absorption, Distribution, Metabolism, and Excretion: From the Bench to the Bedside - Clinical Pharmacology Considerations.

    PubMed

    Ronaldson, P T; Bauer, B; El-Kattan, A F; Shen, H; Salphati, L; Louie, S W

    2016-11-01

    The American Association of Pharmaceutical Scientists/International Transporter Consortium Joint Workshop on Drug Transporters in absorption, distribution, metabolism, and excretion was held with the objective of discussing innovative advances in transporter pharmacology. Specific topics included (i) transporters at the blood-brain barrier (BBB); (ii) emerging transport proteins; (iii) recent advances in achieving hepatoselectivity and optimizing clearance for organic anion-transporting polypeptide (OATP) substrates; (iv) utility of animal models for transporter studies; and (v) clinical correlation of transporter polymorphisms. Here, we present state-of-the-art highlights from this workshop in these key areas of focus.

  19. Extending the X Window System

    SciTech Connect

    Brenkosh, J.P.

    1993-12-23

    The X Window System was originally developed in 1984 at Massachusetts Institute of Technology. It provides client-server computing functionality and also facilitates the establishment of a distributed computing environment. Since its inception the X Window System has undergone many enhancements. Despite these enhancements there will always be a functionality desired in the standard released version of X that is not supported or commercially or academically available. The developers of the X Window System have designed it in such a way that it is possible to add functionality that is not included in the standard release. This is called an extension. Extensions are one method used to develop a customized version of the X Window System to support a specialized application. This report presents the mechanics of adding an extension and examines a particular extension that was developed at Sandia National Laboratories to support data compression in X Windows which was one aspect of the Desktop Video and Collaborative Engineering Laboratory Directed Research and Development (LDRD).

  20. Switchable Materials for Smart Windows.

    PubMed

    Wang, Yang; Runnerstrom, Evan L; Milliron, Delia J

    2016-06-07

    This article reviews the basic principles of and recent developments in electrochromic, photochromic, and thermochromic materials for applications in smart windows. Compared with current static windows, smart windows can dynamically modulate the transmittance of solar irradiation based on weather conditions and personal preferences, thus simultaneously improving building energy efficiency and indoor human comfort. Although some smart windows are commercially available, their widespread implementation has not yet been realized. Recent advances in nanostructured materials provide new opportunities for next-generation smart window technology owing to their unique structure-property relations. Nanomaterials can provide enhanced coloration efficiency, faster switching kinetics, and longer lifetime. In addition, their compatibility with solution processing enables low-cost and high-throughput fabrication. This review also discusses the importance of dual-band modulation of visible and near-infrared (NIR) light, as nearly 50% of solar energy lies in the NIR region. Some latest results show that solution-processable nanostructured systems can selectively modulate the NIR light without affecting the visible transmittance, thus reducing energy consumption by air conditioning, heating, and artificial lighting.

  1. A modified emulsion gelation technique to improve buoyancy of hydrogel tablets for floating drug delivery systems.

    PubMed

    Yom-Tov, Ortal; Seliktar, Dror; Bianco-Peled, Havazelet

    2015-10-01

    The use of buoyant or floating hydrogel tablets is of particular interest in the sustained release of drugs to the stomach. They have an ability to slow the release rates of drugs by prolonging their absorption window in the upper part of the gastrointestinal (GI) tract. In this study we synthesized bioactive hydrogels that have sustainable release rates for drugs in the stomach based on a hydrogel preparation technique that employs emulsifying surfactants. The emulsion gelation technique, which encapsulates oil droplets within the hydrogels during crosslinking, was used to decrease their specific gravity in aqueous environments, resulting in floating drug release depots. Properties such as swelling, buoyancy, density and drug release were manipulated by changing the polymer concentrations, surfactant percentages and the oil:polymer ratios. The relationship between these properties and the hydrogel's floating lag time was documented. The potential for this material to be used as a floating drug delivery system was demonstrated.

  2. Windows and daylighting: A brighter outlook

    SciTech Connect

    Not Available

    1994-11-01

    This is an overview of energy efficient window glazing and framing technology. The topics of the report include: windows and energy use, a point of view; a challenging federal opportunity; DOE window research; advanced optical technologies such as spectrally selective glazing, switchable glazing, super windows with low-emissivity coatings and noble gas fills; and performance evaluation and design tools.

  3. Music@Microsoft.Windows: Composing Ambience

    ERIC Educational Resources Information Center

    Rickert, Thomas

    2010-01-01

    It is well known, of course, that all Windows versions except for 3.1 have a brief (four to six second) piece of music indicating that Windows is booted and ready for use. While the music may indicate Windows has booted, it bears no immediately discernable relation to the various uses we might actually put Windows to--working, gaming,…

  4. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Window form. 455.3 Section 455.3 Commercial... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form...) Incorporated into contract. The information on the final version of the window form is incorporated into...

  5. Oscillatory integration windows in neurons

    PubMed Central

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-01-01

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720

  6. Oscillatory integration windows in neurons.

    PubMed

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-12-15

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.

  7. User Data Package - Energy-Efficient Windows and Window Coverings for Naval Housing

    DTIC Science & Technology

    1990-07-01

    This should be evaluated using cost vs . savings analysis, as shown in the UDP. " It is recommended that window installation be performed by qualified and...1 1.2 IMPLEMENTATION PLAN............................................ 2 2. FUNCTION AND PERFORMANCE OF WINDOWS AND WINDOW ...113 Appendix D - ( Performance Data for Some Whole Window Units Without Window Coverings

  8. Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

    SciTech Connect

    King, A.B.; Schwartz, R.

    1987-04-01

    Ethambutol, (CH/sub 3/CH/sub 2/-CH(CH/sub 2/OH)-NH-CH/sub 2/)/sub 2/ (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by /sup 65/Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, /sup 65/Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption.

  9. Design and comparison of laser windows for high-power lasers

    NASA Astrophysics Data System (ADS)

    Niu, Yanxiong; Liu, Wenwen; Liu, Haixia; Wang, Caili; Niu, Haisha; Man, Da

    2014-11-01

    High-power laser systems are getting more and more widely used in industry and military affairs. It is necessary to develop a high-power laser system which can operate over long periods of time without appreciable degradation in performance. When a high-energy laser beam transmits through a laser window, it is possible that the permanent damage is caused to the window because of the energy absorption by window materials. So, when we design a high-power laser system, a suitable laser window material must be selected and the laser damage threshold of the window must be known. In this paper, a thermal analysis model of high-power laser window is established, and the relationship between the laser intensity and the thermal-stress field distribution is studied by deducing the formulas through utilizing the integral-transform method. The influence of window radius, thickness and laser intensity on the temperature and stress field distributions is analyzed. Then, the performance of K9 glass and the fused silica glass is compared, and the laser-induced damage mechanism is analyzed. Finally, the damage thresholds of laser windows are calculated. The results show that compared with K9 glass, the fused silica glass has a higher damage threshold due to its good thermodynamic properties. The presented theoretical analysis and simulation results are helpful for the design and selection of high-power laser windows.

  10. VIS-IR transmitting windows

    NASA Astrophysics Data System (ADS)

    Bayya, S. S.; Chin, G. D.; Villalobos, G.; Sanghera, J. S.; Aggarwal, I. D.

    2005-05-01

    The U.S. Naval Research Laboratory (NRL) has developed two unique materials with excellent properties for various military and commercial applications in the UV-Vis-IR wavelength range. These materials are: an amorphous Barium Gallo-Germanate (BGG) glass and a polycrystalline Magnesium Aluminate Spinel. The BGG glass is made using traditional glass melting techniques, and was developed as a low cost alternative to the currently used window materials. Large prototype windows have been fabricated for a Navy reconnaissance program. BGG windows have been successfully tested for environmental ruggedness (MIL-F-48616) and rain erosion durability up to 300 mph. BGG glass is currently under development and evaluation for High Energy Laser (HEL) applications. A new process has been developed to sinter spinel to clear transparency with very high yields. This process has been used to make various sizes and shapes (flats and domes) and is readily scalable to industrial sizes to produce large windows & domes for various applications. NRL has also developed modified BGG glasses, which are compatible with Spinel and ALON substrates for bonding.

  11. Closing the Windows on Opportunity.

    ERIC Educational Resources Information Center

    Coombs, Norman

    1995-01-01

    The rapid adoption of graphic user interface (GUI), as indicated by Microsoft's Windows95 and the Internet's increased use of graphics, is threatening information technology opportunities for people with disabilities. Recent legislation requires that schools provide access to computers and information technology, and producers of Mosaic are…

  12. The Benefits of Aluminum Windows.

    ERIC Educational Resources Information Center

    Goyal, R. C.

    2002-01-01

    Discusses benefits of aluminum windows for college construction and renovation projects, including that aluminum is the most successfully recycled material, that it meets architectural glass deflection standards, that it has positive thermal energy performance, and that it is a preferred exterior surface. (EV)

  13. Total Library Computerization for Windows.

    ERIC Educational Resources Information Center

    Combs, Joseph, Jr.

    1999-01-01

    Presents a general review of features of version 2.1 of Total Library Computerization (TLC) for Windows from On Point, Inc. Includes information about pricing, hardware and operating systems, modules/functions available, user interface, security, on-line catalog functions, circulation, cataloging, and documentation and online help. A table…

  14. Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination.

    PubMed

    Jones, Christopher R; Hatley, Oliver J D; Ungell, Anna-Lena; Hilgendorf, Constanze; Peters, Sheila Annie; Rostami-Hodjegan, Amin

    2016-05-01

    Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5'-diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.g. zonal distribution), protein homology and relative abundances and how these differ across species is important for building models of human metabolic extraction. The focus of this manuscript is to explore the parameters influencing bioavailability and to consider how well these are predicted in human from animal models or from in vitro to in vivo extrapolation. A unique retrospective analysis of three AstraZeneca molecules progressed to first in human PK studies is used to highlight the impact that species differences in gut wall metabolism can have on predicted human PK. Compared to the liver, pharmaceutical research has further to go in terms of adopting a common approach for characterisation and quantitative prediction of intestinal metabolism. A broad strategy is needed to integrate assessment of intestinal metabolism in the context of typical DMPK activities ongoing within drug discovery programmes up until candidate drug nomination.

  15. Optical Window Materials For Hypersonic Flow

    NASA Astrophysics Data System (ADS)

    Au, Robert H.

    1989-09-01

    Optical window materials were investigated for infrared sensor systems used in observing ground targets from a hypersonic-glide vehicle. The equilibrium temperature of the window in the glide region depends on the emissivity and varied between 1,370 and 2,250 K. The high temperatures showed that a protective cover over the window is required during the entire glide region of the trajectory. Ejection of the window cover at 70-kft altitude in the terminal region was assumed, resulting in maximum window temperatures of 565 K and 592 K for magnesium oxide and diamond windows, respectively, both 0.8-in thick. The window temperatures for germanium and sapphire were also calculated. Thermal shock, thermal expansion, the effects of the window radiation on the infrared detectors and methods to reduce the hot window problem were examined.

  16. PERITONEAL ABSORPTION

    PubMed Central

    Hahn, P. F.; Miller, L. L.; Robscheit-Robbins, F. S.; Bale, W. F.; Whipple, G. H.

    1944-01-01

    The absorption of red cells from the normal peritoneum of the dog can be demonstrated by means of red cells labeled with radio-iron incorporated in the hemoglobin of these red cells. Absorption in normal dogs runs from 20 to 100 per cent of the amount given within 24 hours. Dogs rendered anemic by bleeding absorb red cells a little less rapidly—ranging from 5 to 80 per cent of the injected red cells. Doubly depleted dogs (anemic and hypoproteinemic) absorb even less in the three experiments recorded. This peritoneal absorption varies widely in different dogs and even in the same dog at different times. We do not know the factors responsible for these variations but there is no question about active peritoneal absorption. The intact red cells pass readily from the peritoneal cavity into lymph spaces in diaphragm and other areas of the peritoneum. The red cells move along the lymphatics and through the lymph glands with little or no phagocytosis and eventually into the large veins through the thoracic ducts. PMID:19871404

  17. Removable Window System for Space Vehicles

    NASA Technical Reports Server (NTRS)

    Grady, James P. (Inventor)

    2015-01-01

    A window system for a platform comprising a window pane, a retention frame, and a biasing system. The window pane may be configured to contact a sealing system. The retention frame may be configured to contact the sealing system and hold the window pane against the support frame. The biasing system may be configured to bias the retention frame toward the support frame while the support frame and the retention frame are in a configuration that holds the window pane. Removal of the biasing system may cause the retention frame and the window pane to be removable.

  18. Measured winter performance of storm windows

    SciTech Connect

    Klems, Joseph H.

    2002-08-23

    Direct comparison measurements were made between various prime/storm window combinations and a well-weatherstripped, single-hung replacement window with a low-E selective glazing. Measurements were made using an accurate outdoor calorimetric facility with the windows facing north. The doublehung prime window was made intentionally leaky. Nevertheless, heat flows due to air infiltration were found to be small, and performance of the prime/storm combinations was approximately what would be expected from calculations that neglect air infiltration. Prime/low-E storm window combinations performed very similarly to the replacement window. Interestingly, solar heat gain was not negligible, even in north-facing orientation.

  19. Laser absorption phenomena in flowing gas devices

    NASA Technical Reports Server (NTRS)

    Chapman, P. K.; Otis, J. H.

    1976-01-01

    A theoretical and experimental investigation is presented of inverse Bremsstrahlung absorption of CW CO2 laser radiation in flowing gases seeded with alkali metals. In order to motivate this development, some simple models are described of several space missions which could use laser powered rocket vehicles. Design considerations are given for a test call to be used with a welding laser, using a diamond window for admission of laser radiation at power levels in excess of 10 kW. A detailed analysis of absorption conditions in the test cell is included. The experimental apparatus and test setup are described and the results of experiments presented. Injection of alkali seedant and steady state absorption of the laser radiation were successfully demonstrated, but problems with the durability of the diamond windows at higher powers prevented operation of the test cell as an effective laser powered thruster.

  20. High-efficiency nanostructured window GaAs solar cells.

    PubMed

    Liang, Dong; Kang, Yangsen; Huo, Yijie; Chen, Yusi; Cui, Yi; Harris, James S

    2013-10-09

    Nanostructures have been widely used in solar cells due to their extraordinary optical properties. In most nanostructured cells, high short circuit current has been obtained due to enhanced light absorption. However, most of them suffer from lowered open circuit voltage and fill factor. One of the main challenges is formation of good junction and electrical contact. In particular, nanostructures in GaAs only have shown unsatisfactory performances (below 5% in energy conversion efficiency) which cannot match their ideal material properties and the record photovoltaic performances in industry. Here we demonstrate a completely new design for nanostructured solar cells that combines nanostructured window layer, metal mesa bar contact with small area, high quality planar junction. In this way, we not only keep the advanced optical properties of nanostructures such as broadband and wide angle antireflection, but also minimize its negative impact on electrical properties. High light absorption, efficient carrier collection, leakage elimination, and good lateral conductance can be simultaneously obtained. A nanostructured window cell using GaAs junction and AlGaAs nanocone window demonstrates 17% energy conversion efficiency and 0.982 V high open circuit voltage.

  1. Biopharmaceutic classification of drugs revisited.

    PubMed

    Daousani, Chrysa; Macheras, Panos

    2016-12-01

    The biopharmaceutics classification system (BCS) was based on the tube model of the intestinal lumen. This model considers constant drug permeability along the intestines, a plug flow fluid with the suspended drug particles moving with the fluid, and dissolution in the small particle limit. Since then the research work focusing on drug gastrointestinal (GI) absorption phenomena and processes rely on the classical laws of transport, diffusion and kinetics; however, the homogeneous assumptions associated with the well-stirred Euclidean media, where the classical laws of diffusion and kinetics apply, have been questioned in the past. In this work we explore the biopharmaceutic classification of drugs using a heterogeneous pseudo steady-state model of oral drug absorption. The fraction of dose absorbed (Fabs) was expressed as a function of two time-dependent processes where time dependent coefficients govern drug absorption and non-absorption processes. Fundamental drug properties like the absorption potential are correlated with Fabs and allow the biopharmaceutic classification of drugs taking into account the heterogeneous aspects of oral drug absorption. This analysis reveals that for Class I drugs no time dependency is expected for both absorption and non absorption processes since the gastric emptying is controlling the absorption of Class I drugs while the completion of absorption (Fabs>90%) is terminated along the first part of the jejunum. Due to the biopharmaceutical properties of Class II, III and IV drugs, these drugs travel throughout the GI tract and therefore both absorption and non absorption processes will exhibit time dependency. Thus, the calculation of Fabs (<90%) for Class II, III and IV is dependent on the estimates of the time exponents of time dependent coefficients controlling drug absorption e.g. dissolution, uptake or non absorption e.g. precipitation.

  2. Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

    PubMed

    Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

    2014-10-01

    This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation.

  3. Windows in the Milky Way

    NASA Technical Reports Server (NTRS)

    Waller, William H.; Tacconi-Garman, Lowell Evan; Boulanger, Francois; Okumura, Koryo

    1991-01-01

    The objectives were twofold: (1) to study the IRAS emission levels in the vicinity of Baade's Window and in other optically transparent regions near the Galactic Center; and (2) to study the IRAS emission levels along sightlines in the Milky Way that exhibit very little CO emission. Tests were attempted to see whether the optically transparent 'windows' near the Galactic center can be identified (as FIR-weak regions) in the IRAS data base; and if so, whether the CO weak regions found elsewhere in the Milky Way represent similarly FIR weak and thus optically transparent sightlines through the Galaxy. The CO weak regions were also targeted in an effort to study the diffuse intercloud dust and its warming by the interstellar radiation field.

  4. Electrochromic Windows: Advanced Processing Technology

    SciTech Connect

    SAGE Electrochromics, Inc

    2006-12-13

    This project addresses the development of advanced fabrication capabilities for energy saving electrochromic (EC) windows. SAGE EC windows consist of an inorganic stack of thin films deposited onto a glass substrate. The window tint can be reversibly changed by the application of a low power dc voltage. This property can be used to modulate the amount of light and heat entering buildings (or vehicles) through the glazings. By judicious management of this so-called solar heat gain, it is possible to derive significant energy savings due to reductions in heating lighting, and air conditioning (HVAC). Several areas of SAGE’s production were targeted during this project to allow significant improvements to processing throughput, yield and overall quality of the processing, in an effort to reduce the cost and thereby improve the market penetration. First, the overall thin film process was optimized to allow a more robust set of operating points to be used, thereby maximizing the yield due to the thin film deposition themselves. Other significant efforts aimed at improving yield were relating to implementing new procedures and processes for the manufacturing process, to improve the quality of the substrate preparation, and the quality of the IGU fabrication. Furthermore, methods for reworking defective devices were developed, to enable devices which would otherwise be scrapped to be made into useful product. This involved the in-house development of some customized equipment. Finally, the improvements made during this project were validated to ensure that they did not impact the exceptional durability of the SageGlass® products. Given conservative estimates for cost and market penetration, energy savings due to EC windows in residences in the US are calculated to be of the order 0.026 quad (0.026×1015BTU/yr) by the year 2017.

  5. Evaluation of ALON for cannon window application

    NASA Astrophysics Data System (ADS)

    Beyer, Richard A.; Kerwien, Henry

    1999-07-01

    In the application of laser ignition to large caliber cannons, a critical element is the window into the cannon chamber to admit the laser energy. This window must repeatedly withstand a particularly harsh environment of highly reactive high temperature combustion products from the gun propeller at pressures up to 440 MPa. Failure of the window can be caused by either thermal gradients in the window or mechanical force, or a combustion. Previous successes with single-crystal sapphire have sometimes been limited by window deterioration modes suggestive of crystalline behavior. Samples of ALON have been fabricated in the same design as the standard sapphire windows and were qualified for gun testing. This process involves a series of experiments in a closed chamber where gun propellant is burned to generate an environment similar to that inside the gun. Windows mounted in two methods have been tested. One of these windows has survived the full pre-gun test series with no visible damage.

  6. Rugged Ceramic Window for RF Applications

    SciTech Connect

    Neubauer, Michael; Johnson, Rolland P.; Rimmer, Robert; Elliot, Tom; Stirbet, Mircea

    2009-05-04

    High-current RF cavities that are needed for many accelerator applications are often limited by the power transmission capability of the pressure barriers (windows) that separate the cavity from the power source. Most efforts to improve RF window design have focused on alumina ceramic, the most popular historical choice, and have not taken advantage of new materials. Alternative window materials have been investigated using a novel Merit Factor comparison and likely candidates have been tested for the material properties which will enable construction in the self-matched window configuration. Window assemblies have also been modeled and fabricated using compressed window techniques which have proven to increase the power handling capability of waveguide windows. Candidate materials have been chosen to be used in fabricating a window for high power testing at Thomas Jefferson National Accelerator Facility.

  7. RUGGED CERAMIC WINDOW FOR RF APPLICATIONS

    SciTech Connect

    MIKE NEUBAUER

    2012-11-01

    High-current RF cavities that are needed for many accelerator applications are often limited by the power transmission capability of the pressure barriers (windows) that separate the cavity from the power source. Most efforts to improve RF window design have focused on alumina ceramic, the most popular historical choice, and have not taken advantage of new materials. Alternative window materials have been investigated using a novel Merit Factor comparison and likely candidates have been tested for the material properties which will enable construction in the self-matched window configuration. Window assemblies have also been modeled and fabricated using compressed window techniques which have proven to increase the power handling capability of waveguide windows. Candidate materials have been chosen to be used in fabricating a window for high power testing at Thomas Jefferson National Accelerator Facility.

  8. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  9. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  10. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  11. 16 CFR 455.3 - Window form.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Window form. (a) Form given to buyer. Give the buyer of a used vehicle sold by you the window form... coverage agreed upon. If you prefer, you may give the buyer a copy of the original, so long as that...

  12. Low-Absorption Liquid Crystals for Infrared Beam Steering

    DTIC Science & Technology

    2014-10-17

    goals are: ri~0.2 (at-tSilri),*? (at 1 kHz), and absorption coefficient B 5/cm. 15. SUBJECT TERMS Low absorption, MWIR, chlorinated liquid crystals...spectral region of interest by deuteration, fluorination and chlorination ; 2) Employing thin cell gap by choosing a high birefringence liquid crystal...mixture. First, we synthesized several chlorinated terphenyls and made a eutectic mixture showing a low absorption window in the region of 4-5|a.m

  13. Breakdown phenomena in rf windows

    SciTech Connect

    Saito, Y.

    1995-07-05

    The multipactor and flashover phenomena of alumina rf windows used in high-power klystrons have been investigated. Multipactoring due to the high yield of secondary electron emission takes place during rf operation. A spectrum analysis of the luminescence due to multipactoring shows that multipactor electron bombardment causes an F-center of alumina, thus leading to surface melting. From the results of a high-power examination of rf windows with several kinds of alumina ceramics, it was found that an alumina material with a crystallized grain-boundary and without any voids between the boundaries, thus having a low loss-tangent value, is not liable to F-centers, even under multipactoring. Flashovers in a tree-like pattern of alumina luminescence occasionally take place on a TiN-coated surface. From the results of surface-charging measurements and high-power examinations of annealed alumina disks, the flashover phenomenon is considered to be an avalanche of electrons which have been trapped in mechanically introduced defects. The effectivenesses of multipactor-suppressing coatings and of a field-reduced window structure were also examined. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  14. Development of Zinc Sulfide Seeker Window Material

    DTIC Science & Technology

    2007-11-02

    currently valid OMB control number. 1. REPORT DATE 15 JAN 2005 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Development of...contrasting to the currently used THAAD sapphire window and validate the predictions for an alternate seeker window material, multispectral zinc...and validate the capability of multispectral zinc sulfide seeker window material. The use of zinc sulfide as a replacement window for the current

  15. Fourth near-infrared optical window for assessment of bone and other tissues

    NASA Astrophysics Data System (ADS)

    Sordillo, Diana C.; Sordillo, Laura A.; Sordillo, Peter P.; Alfano, Robert R.

    2016-02-01

    Recently, additional near-infrared (NIR) optical windows beyond the conventional first therapeutic window have been utilized for deep tissue imaging through scattering media. Biomedical applications using a second optical window (1100 to 1300 nm) and a third (1600 to 1870 nm) are emerging. A fourth window (2100 to 2300 nm) has been largely ignored due to high water absorption and a lack of high sensitivity imaging detectors and ultrafast laser sources. In this study, optical properties of bone in this fourth NIR optical window, were investigated. Results were compared to those seen at the first, second and third windows, and are consistent with our previous work on malignant and benign breast and prostate tissues. Bone and malignant tissues showed highest uptake in the third and fourth windows. As collagen is a major chromophore with prominent spectral peaks between 2100 and 2300 nm, it may be that the fourth optical window is particularly useful for studying tissues with a higher collagen content, such as bone or malignant tumors.

  16. Double loaded self-decomposable SiO₂ nanoparticles for sustained drug release.

    PubMed

    Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

    2015-10-21

    Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms-the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the "grown-in" drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window-a sustained drug delivery system with a great impact on improving the management of chronic diseases.

  17. Rigid thin windows for vacuum applications

    DOEpatents

    Meyer, Glenn Allyn; Ciarlo, Dino R.; Myers, Booth Richard; Chen, Hao-Lin; Wakalopulos, George

    1999-01-01

    A thin window that stands off atmospheric pressure is fabricated using photolithographic and wet chemical etching techniques and comprises at least two layers: an etch stop layer and a protective barrier layer. The window structure also comprises a series of support ribs running the width of the window. The windows are typically made of boron-doped silicon and silicon nitride and are useful in instruments such as electron beam guns and x-ray detectors. In an electron beam gun, the window does not impede the electrons and has demonstrated outstanding gun performance and survivability during the gun tube manufacturing process.

  18. Purged window apparatus utilizing heated purge gas

    DOEpatents

    Ballard, Evan O.

    1984-01-01

    A purged window apparatus utilizing tangentially injected heated purge gases in the vicinity of electromagnetic radiation transmitting windows, and a tapered external mounting tube to accelerate these gases to provide a vortex flow on the window surface and a turbulent flow throughout the mounting tube. Use of this apparatus prevents backstreaming of gases under investigation which are flowing past the mouth of the mounting tube which would otherwise deposit on the windows. Lengthy spectroscopic investigations and analyses can thereby be performed without the necessity of interrupting the procedures in order to clean or replace contaminated windows.

  19. Space station proximity operations and window design

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    On-orbit proximity operations (PROX-OPS) consist of all extravehicular activity (EVA) within 1 km of the space station. Because of the potentially large variety of PROX-OPS, very careful planning for space station windows is called for and must consider a great many human factors. The following topics are discussed: (1) basic window design philosophy and assumptions; (2) the concept of the local horizontal - local vertical on-orbit; (3) window linear dimensions; (4) selected anthropomorphic considerations; (5) displays and controls relative to windows; and (6) full window assembly replacement.

  20. Casting of Halide and Fluoride Alloys for Laser Windows

    DTIC Science & Technology

    1974-10-15

    a lower temperature (900CC) or by annealing at 1000° C under a better vacuum or under a partial pressure of teflon vapor providing a purifying...castings (3 in. diameter) of SrF2 have been produced with low optical absorption coefficients pi, 5.25 jim. High qurlity CaF2 castings have been...Waltham, Massachusetts under Contract No. F19628-74-C-0148 entitled "Casting of Halide and Fluoride Alloys for Laser Windows. " This work is

  1. NON-INTRUSIVE SENSOR FOR GAS FILL VERIFICATION OF INSULATED GLASS WINDOWS

    SciTech Connect

    Andrew Freedman; Paul L. Kebabian; Richard R. Romano; James Woodroffe

    2003-10-01

    A sensor capable of measuring the amount of oxygen (an unwanted component that is only present because of improper filling or seal failure) within an argon-filled insulated glass window has been designed, built and successfully tested. It operates by using the optical absorption of oxygen in the atmospheric A-band centered at 762 nm. Light emitted by an argon-filled surface glow discharge lamp is Zeeman-tuned on and off an oxygen absorption line using an AC-modulated electromagnet. In the presence of oxygen, the change in the measured intensity of the lamp, obtained using standard demodulation techniques, is proportional to the oxygen column density. Measurements using an industry-standard insulated glass window indicate that the sensor can measure the amount of oxygen in a nominally argon-filled IG window (with a window gap of 10 mm) with a precision of 0.50% oxygen using a 16 second integration time. This level of precision is well within the limits required by the IG window manufacturing industry for proper monitoring of newly manufactured window units.

  2. Drug absorption in vitro model: filter-immobilized artificial membranes. 2. Studies of the permeability properties of lactones in Piper methysticum Forst.

    PubMed

    Avdeef, A; Strafford, M; Block, E; Balogh, M P; Chambliss, W; Khan, I

    2001-12-01

    The assessment of transport properties of 23 drug and natural product molecules was made using the in vitro model based on filter-immobilized artificial membranes (filter-IAM), assembled from phosphatidylcholine in dodecane, in buffer solutions at pH 7.4. Five of the compounds were lactones extracted from the roots of the kava-kava plant. Experiments were designed to test the effects of stirring (0-600 rpm) during assays and the effects of varying the assay times (2-15 h). The highly mobile kava lactones permeated in the order dihydromethisticin (40)>yangonin (37)>kavain (34)>methisticin (32)>desmethoxyyangonin (26), the numbers in parentheses being the measured effective permeabilities in units of 10(-6) cm/s. By comparison, commercial drugs ranked: phenazopyridine (35)>testosterone (19)>propranolol (13)>ketoconazole (6.3)>piroxicam (2.2)>caffeine (1.7)>metoprolol (0.8)>terbutaline (0.01). In addition to permeability measurements, membrane retention of compounds was determined. Yangonin, desmethoxyyangonin, ketoconazole, and phenazopyridine were more than 60% retained by the artificial membranes containing phospholipids. Stirring during assay significantly increased the observed permeabilities for highly mobile molecules, but had minimal impact on the poorly permeable molecules. The influence of hydrogen bonding was explored by determining permeabilities using filters coated with dodecane free of phospholipids. In the filter-IAM method, concentrations were determined by microtitre plate UV spectrophotometry and by LC-MS. Higher-throughput was achieved with direct UV by the use of 96-well microtitre plate formats and with LC-MS by the use of cassette dosing (five-in-one).

  3. Optomechanically induced transparency and absorption in hybridized optomechanical systems

    NASA Astrophysics Data System (ADS)

    Hou, B. P.; Wei, L. F.; Wang, S. J.

    2015-09-01

    We present the normal-mode splitting and optomechanically induced transparency or absorption phenomena in the strongly tunnel-coupled optomechanical cavities. In the probe output spectrum, there appear central transparency windows or absorption peaks around which two broad sidebands are symmetrically located. It has been confirmed by the quantitative findings that two broad sidebands, which include the distorted absorption peaks, indicate the normal-mode splitting of the two hybridized cavities, and central transparency windows or absorption peaks character the interference induced by the optomechanical interactions. Additionally, the switching from absorption to amplification can be realized by only adjusting the tunnel interaction. These spectrum properties can be used for the coherent control of light pulses via microfabricated optomechanical arrays.

  4. Durable coatings for IR windows

    NASA Astrophysics Data System (ADS)

    Goldman, Lee M.; Jha, Santosh K.; Gunda, Nilesh; Cooke, Rick; Agarwal, Neeta; Sastri, Suri A.; Harker, Alan; Kirsch, Jim

    2005-05-01

    Durable coatings of silicon-carbon-oxy-nitride (a.k.a. SiCON) are being developed to protect high-speed missile windows from the environmental loads during flight. Originally developed at Rockwell Scientific Corporation (RSC) these coatings exhibited substantial promise, but were difficult to deposit. Under a DoD DARPA SBIR Phase I program, Surmet Corporation, working closely with RSC, is depositing these coatings using an innovative vacuum vapor deposition process. High rate of coating deposition and the ease of manipulating the process variables, make Surmet"s process suitable for the deposition of substantially thick films (up to 30 μm) with precisely controlled chemistry. Initial work has shown encouraging results, and the refinement of the coating and coating process is still underway. Coupons of SiN and SiCON coatings with varying thickness on a variety of substrates such as Si-wafer, ZnS and ALON were fabricated and used for the study. This paper will present and discuss the results of SiN and SiCON coatings deposition and characterization (physical, mechanical and optical properties) as a basis for evaluating their suitability for high speed missile windows application.

  5. Interferometer for Space Station Windows

    NASA Technical Reports Server (NTRS)

    Hall, Gregory

    2003-01-01

    Inspection of space station windows for micrometeorite damage would be a difficult task insitu using current inspection techniques. Commercially available optical profilometers and inspection systems are relatively large, about the size of a desktop computer tower, and require a stable platform to inspect the test object. Also, many devices currently available are designed for a laboratory or controlled environments requiring external computer control. This paper presents an approach using a highly developed optical interferometer to inspect the windows from inside the space station itself using a self- contained hand held device. The interferometer would be capable as a minimum of detecting damage as small as one ten thousands of an inch in diameter and depth while interrogating a relatively large area. The current developmental state of this device is still in the proof of concept stage. The background section of this paper will discuss the current state of the art of profilometers as well as the desired configuration of the self-contained, hand held device. Then, a discussion of the developments and findings that will allow the configuration change with suggested approaches appearing in the proof of concept section.

  6. Downsampling Photodetector Array with Windowing

    NASA Technical Reports Server (NTRS)

    Patawaran, Ferze D.; Farr, William H.; Nguyen, Danh H.; Quirk, Kevin J.; Sahasrabudhe, Adit

    2012-01-01

    In a photon counting detector array, each pixel in the array produces an electrical pulse when an incident photon on that pixel is detected. Detection and demodulation of an optical communication signal that modulated the intensity of the optical signal requires counting the number of photon arrivals over a given interval. As the size of photon counting photodetector arrays increases, parallel processing of all the pixels exceeds the resources available in current application-specific integrated circuit (ASIC) and gate array (GA) technology; the desire for a high fill factor in avalanche photodiode (APD) detector arrays also precludes this. Through the use of downsampling and windowing portions of the detector array, the processing is distributed between the ASIC and GA. This allows demodulation of the optical communication signal incident on a large photon counting detector array, as well as providing architecture amenable to algorithmic changes. The detector array readout ASIC functions as a parallel-to-serial converter, serializing the photodetector array output for subsequent processing. Additional downsampling functionality for each pixel is added to this ASIC. Due to the large number of pixels in the array, the readout time of the entire photodetector is greater than the time between photon arrivals; therefore, a downsampling pre-processing step is done in order to increase the time allowed for the readout to occur. Each pixel drives a small counter that is incremented at every detected photon arrival or, equivalently, the charge in a storage capacitor is incremented. At the end of a user-configurable counting period (calculated independently from the ASIC), the counters are sampled and cleared. This downsampled photon count information is then sent one counter word at a time to the GA. For a large array, processing even the downsampled pixel counts exceeds the capabilities of the GA. Windowing of the array, whereby several subsets of pixels are designated

  7. ABSORPTION ANALYZER

    DOEpatents

    Brooksbank, W.A. Jr.; Leddicotte, G.W.; Strain, J.E.; Hendon, H.H. Jr.

    1961-11-14

    A means was developed for continuously computing and indicating the isotopic assay of a process solution and for automatically controlling the process output of isotope separation equipment to provide a continuous output of the desired isotopic ratio. A counter tube is surrounded with a sample to be analyzed so that the tube is exactly in the center of the sample. A source of fast neutrons is provided and is spaced from the sample. The neutrons from the source are thermalized by causing them to pass through a neutron moderator, and the neutrons are allowed to diffuse radially through the sample to actuate the counter. A reference counter in a known sample of pure solvent is also actuated by the thermal neutrons from the neutron source. The number of neutrons which actuate the detectors is a function of a concentration of the elements in solution and their neutron absorption cross sections. The pulses produced by the detectors responsive to each neu tron passing therethrough are amplified and counted. The respective times required to accumulate a selected number of counts are measured by associated timing devices. The concentration of a particular element in solution may be determined by utilizing the following relation: T2/Ti = BCR, where B is a constant proportional to the absorption cross sections, T2 is the time of count collection for the unknown solution, Ti is the time of count collection for the pure solvent, R is the isotopic ratlo, and C is the molar concentration of the element to be determined. Knowing the slope constant B for any element and when the chemical concentration is known, the isotopic concentration may be readily determined, and conversely when the isotopic ratio is known, the chemical concentrations may be determined. (AEC)

  8. Challenger Center's Window on the Universe

    NASA Astrophysics Data System (ADS)

    Livengood, T. A.; Goldstein, J. J.; Smith, S.; Bobrowsky, M.; Radnofsky, M.; Perelmuter, J.-M.; Jaggar, L.

    2001-11-01

    Challenger Center for Space Science Education's Window on the Universe program aims to create a network of under-served communities across the nation dedicated to sustained science, math, and technology education. Window communities presently include Broken Arrow, OK; Muncie, IN; Moscow, ID; Nogales, AZ; Tuskegee, AL; Marquette, MI; Altamont, KS; Washington, D.C.; and other emerging sites. Window uses themes of human space flight and the space sciences as interdisciplinary means to inspire entire communities. Practicing scientists and engineers engaged in these disciplines are invited to volunteer to become a part of these communities for a week, each visitor reaching roughly 2000 K-12 students through individual classroom visits and Family Science Night events during an intense Window on the Universe Week. In the same Window Week, Challenger Center scientists and educators present a workshop for local educators to provide training in the use of a K-12 educational module built around a particular space science and exploration theme. Window communities follow a 3-year development: Year 1, join the network, experience Window Week presented by Challenger Center and visiting researchers; Year 2, same as Year 1 plus workshop on partnering with local organizations to develop sources of visiting researchers and to enhance connections with local resources; Year 3 and subsequent, the community stages its own Window Week, with Challenger Center providing new education modules and training workshops for "master educators" from the Window community, after which the master educators return home to conduct training workshops of their own. Challenger Center remains a resource and clearinghouse for Window communities to acquire experience, technical information, and opportunities for distance collaboration with other Window communities. Window on the Universe is dedicated to assessing degree of success vs. failure in each program component and as a whole, using pre- and post

  9. A Novel Murine Model for the In Vivo Study of Transdermal Drug Penetration

    PubMed Central

    Erős, Gábor; Hartmann, Petra; Berkó, Szilvia; Csizmazia, Eszter; Csányi, Erzsébet; Sztojkov-Ivanov, Anita; Németh, István; Szabó-Révész, Piroska; Zupkó, István; Kemény, Lajos

    2012-01-01

    Enhancement of the transdermal penetration of different active agents is an important research goal. Our aim was to establish a novel in vivo experimental model which provides a possibility for exact measurement of the quantity of penetrated drug. The experiments were performed on SKH-1 hairless mice. A skin fold in the dorsal region was fixed with two fenestrated titanium plates. A circular wound was made on one side of the skin fold. A metal cylinder with phosphate buffer was fixed into the window of the titanium plate. The concentration of penetrated drug was measured in the buffer. The skin fold was morphologically intact and had a healthy microcirculation. The drug appeared in the acceptor buffer after 30 min, and its concentration exhibited a continuous increase. The presence of ibuprofen was also detected in the plasma. In conclusion, this model allows an exact in vivo study of drug penetration and absorption. PMID:22272176

  10. Simultaneous multi-residue determination of twenty one veterinary drugs in poultry litter by modeling three-way liquid chromatography with fluorescence and absorption detection data.

    PubMed

    Teglia, Carla M; Peltzer, Paola M; Seib, Silvia N; Lajmanovich, Rafael C; Culzoni, María J; Goicoechea, Héctor C

    2017-05-15

    A method for the simultaneous investigation of twenty one veterinary active ingredients in poultry litter based on MCR-ALS modeling of three-way liquid chromatography with fluorescence and UV detection data is presented. The chromatographic procedure was optimized in terms of both the nature of the organic solvent and the pH of the mobile phase to maximize the resolution of the analytes. In order to improve the simultaneous extraction efficiency of the twenty one veterinary drugs, a simplex-centroid design with combinations of the three components of the extracting mixture, i.e. MeOH, ACN and sodium phosphate buffer 10mmolL(-1) pH =3.50, was carried out. The second-order advantage was exploited in the analysis of highly complex samples containing unmodeled components. The qualitative and quantitative results showed that the application of MCR-ALS was appropriate to resolve highly overlapped peaks in the presence of unknown matrix compounds. Limits of quantification, relative errors of prediction (REP) and average recoveries ranging from 0.02 to 0.61µgg(-1), 3.09-9.35% and 91.0-105.6%, respectively, were obtained. Eventually, the method was successfully applied to the determination of active ingredients in five poultry litter samples collected from different poultry livestock in Argentina.

  11. Monitored Energy Performance of Electrochromic Windows Controlledfor Daylight and Visual Comfort

    SciTech Connect

    Lee, Eleanor S.; DiBartolomeo, Dennis L.; Klems, Joseph; Yazdanian, Mehry; Selkowitz, Stephen E.

    2005-09-23

    A 20-month field study was conducted to measure the energy performance of south-facing large-area tungsten-oxide absorptive electrochromic (EC) windows with a broad switching range in a private office setting. The EC windows were controlled by a variety of means to bring in daylight while minimizing window glare. For some cases, a Venetian blind was coupled with the EC window to block direct sun. Some tests also involved dividing the EC window wall into zones where the upper EC zone was controlled to admit daylight while the lower zone was controlled to prevent glare yet permit view. If visual comfort requirements are addressed by EC control and Venetian blinds, a 2-zone EC window configuration provided average daily lighting energy savings of 10 {+-} 15% compared to the reference case with fully lowered Venetian blinds. Cooling load reductions were 0 {+-} 3%. If the reference case assumes no daylighting controls, lighting energy savings would be 44 {+-} 11%. Peak demand reductions due to window cooling load, given a critical demand-response mode, were 19-26% maximum on clear sunny days. Peak demand reductions in lighting energy use were 0% or 72-100% compared to a reference case with and without daylighting controls, respectively. Lighting energy use was found to be very sensitive to how glare and sun is controlled. Additional research should be conducted to fine-tune EC control for visual comfort based on solar conditions so as to increase lighting energy savings.

  12. Terahertz absorption spectra of highly energetic chemicals

    NASA Astrophysics Data System (ADS)

    Slingerland, E. J.; Vallon, M. K.; Jahngen, E. G. E.; Giles, R. H.; Goyette, T. M.

    2010-04-01

    Research into absorption spectra is useful for detecting chemicals in the field. Each molecule absorbs a set of specific frequencies, which are dependent on the molecule's structure. While theoretical models are available for predicting the absorption frequencies of a particular molecule, experimental measurements are a more reliable method of determining a molecule's actual absorption behavior. The goal of this research is to explore chemical markers (absorption frequencies) that can be used to identify highly energetic molecules of interest to the remote sensing community. Particular attention was paid to the frequency ranges located within the terahertz transmission windows of the atmosphere. In addition, theoretical derivations, with the purpose of calculating the detection limits of such chemicals, will also be presented.

  13. Flexible peritoneal windows for quantitative fluorescence and bioluminescence preclinical imaging.

    PubMed

    Souris, Jeffrey S; Hickson, Jonathan A; Msezane, Lambda; Rinker-Schaeffer, Carrie W; Chen, Chin-Tu

    2013-01-01

    At present, there is considerable interest in the use of in vivo fluorescence and bioluminescence imaging to track the onset and progression of pathologic processes in preclinical models of human disease. Optical quantitation of such phenomena, however, is often problematic, frequently complicated by the overlying tissue's scattering and absorption of light, as well as the presence of endogenous cutaneous and subcutaneous fluorophores. To partially circumvent this information loss, we report here the development of flexible, surgically implanted, transparent windows that enhance quantitative in vivo fluorescence and bioluminescence imaging of optical reporters. These windows are metal and glass free and thus compatible with computed tomography, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography; they also permit visualization of much larger areas with fewer impediments to animal locomotion and grooming than those previously described. To evaluate their utility in preclinical imaging, we surgically implanted these windows in the abdominal walls of female athymic nude mice and subsequently inoculated each animal with 1 × 10(4) to 1 × 10(6) bioluminescent human ovarian cancer cells (SKOV3ip.1-luc). Longitudinal imaging studies of fenestrated animals revealed up to 48-fold gains in imaging sensitivity relative to nonfenestrated animals, with relatively few complications, allowing wide-field in vivo visualization of nascent metastatic ovarian cancer colonization.

  14. PAMPA--a drug absorption in vitro model 11. Matching the in vivo unstirred water layer thickness by individual-well stirring in microtitre plates.

    PubMed

    Avdeef, Alex; Nielsen, Per E; Tsinman, Oksana

    2004-08-01

    Many plate-based in vitro assays of membrane permeability (e.g., Caco-2, MDCK, PAMPA) of sparingly soluble candidate molecules report permeability of water, and not of the intended membrane barrier. This is so because the unstirred water layer on both sides of the membrane barrier is rate limiting for these highly permeable molecules. The thickness of this water layer can be 1500-4000 microm in unstirred assays. Under in vivo conditions, however, the unstirred water layer is believed to be 30-100 microm thick. Lightly stirred in vitro assays, using plate shakers, cannot lower the thickness of the water layer to match that found in vivo. In this study, 55 lipophilic drugs were employed to characterize the effect of stirring in parallel artificial membrane permeability assay (PAMPA). Highly efficient individual-well magnetic stirring at speeds greater than 110 rpm has been demonstrated to lower the unstirred water layer thickness to the in vivo range. Stirring at 622 rpm has lowered the layer thickness to 13 microm in some cases, which had not been previously achieved for plate-based permeability assays. With diminished water layer contribution at 622 rpm, for example, the effective permeability of progesterone is 2754 x 10(-6) cm/s. The new stirring apparatus used in this study is not only suitable for PAMPA, but can also be used in Caco-2 assays. Because of the diminished resistance of the thinner water layer, the stirred PAMPA permeation time has decreased from the usual 15 h to about 15 min for lipophilic compounds.

  15. Triplet absorption spectroscopy and electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Ghafoor, F.; Nazmitdinov, R. G.

    2016-09-01

    Coherence phenomena in a four-level atomic system, cyclically driven by three coherent fields, are investigated thoroughly at zero and weak magnetic fields. Each strongly interacting atomic state is converted to a triplet due to a dynamical Stark effect. Two dark lines with a Fano-like profile arise in the triplet absorption spectrum with anomalous dispersions. We provide conditions to control the widths of the transparency windows by means of the relative phase of the driving fields and the intensity of the microwave field, which closes the optical system loop. The effect of Doppler broadening on the results of the triplet absorption spectroscopy is analysed in detail.

  16. Laser sealed vacuum insulation window

    DOEpatents

    Benson, David K.; Tracy, C. Edwin

    1987-01-01

    A laser sealed evacuated window panel is comprised of two glass panes held spaced apart in relation to each other by a plurality of spherical glass beads and glass welded around the edges to provide an evacuated space between the glass panes that is completely glass sealed from the exterior. The glass welded edge seal is obtained by welding the edges of the glass panes together with a laser beam while the glass panes and bead spacers are positioned in a vacuum furnace and heated to the annealing point of the glass to avoid stress fracture in the area of the glass weld. The laser welding in the furnace can be directed around the perimeter of the glass panel by a combination of rotating the glass panel and linearly translating or aiming the laser with a relay mirror.

  17. Laser sealed vacuum insulating window

    DOEpatents

    Benson, D.K.; Tracy, C.E.

    1985-08-19

    A laser sealed evacuated window panel is comprised of two glass panes held spaced apart in relation to each other by a plurality of spherical glass beads and glass welded around the edges to provide an evacuated space between the glass panes that is completely glass sealed from the exterior. The glass welded edge seal is obtained by welding the edges of the glass panes together with a laser beam while the glass panes and bead spacers are positioned in a vacuum furnace and heated to the annealing point of the glass to avoid stress fracture in the area of the glass weld. The laser welding in the furnace can be directed around the perimeter of the galss panel by a combination of rotating the glass panel and linearly translating or aiming the laser with a relay mirror.

  18. Analysis of surface contaminants on beryllium windows

    SciTech Connect

    Gmur, N.F.

    1986-12-01

    It is known that various crystalline and liquid compounds form on the downstream surfaces of beryllium windows exposed to air. It is also known that the integrity of such windows may be compromised resulting in leaks through the window. The purpose of this report is to document the occurrences described as they pertain to the NSLS and to analyze, where possible, the various substances formed.

  19. Window Observational Rack Facility (WORF)

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Developed by Boeing, at the Marshall Space Flight Center (MSFC) Space Station Manufacturing building, the Window Observational Rack Facility (WORF) will help Space Station crews take some of the best photographs ever snapped from an orbiting spacecraft by eliminating glare and allowing researchers to control their cameras and other equipment from the ground. The WORF is designed to make the best possible use of the high-quality research window in the Space Station's U.S. Destiny laboratory module. Engineers at the MSFC proposed a derivative of the EXPRESS (Expedite the Processing of Experiments to the Space Station) Rack already used on the Space Station and were given the go-ahead. The EXPRESS rack can hold a wide variety of experiments and provide them with power, communications, data, cooling, fluids, and other utilities - all the things that Earth-observing experiment instruments would need. WORF will supply payloads with power, data, cooling, video downlink, and stable, standardized interfaces for mounting imaging instruments. Similar to specialized orbital observatories, the interior of the rack is sealed against light and coated with a special low-reflectant black paint, so payloads will be able to observe low-light-level subjects such as the faint glow of auroras. Cameras and remote sensing instruments in the WORF can be preprogrammed, controlled from the ground, or operated by a Station crewmember by using a flexible shroud designed to cinch tightly around the crewmember's waist. The WORF is scheduled to be launched aboard the STS-114 Space Shuttle mission in the year 2003.

  20. Exploring Canine-Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo Absorption and Dissolution in Dogs.

    PubMed

    Martinez, M N; Mistry, B; Lukacova, V; Lentz, K A; Polli, J E; Hoag, S W; Dowling, T; Kona, R; Fahmy, R M

    2017-03-06

    This study explored the in vivo performance of three oral ciprofloxacin formulations (oral solution, fast, or slow dissolving tablets) in beagle dogs. The in vivo absorption and dissolution behaviors, estimated with in silico mechanistic models, were compared to the results previously published in human volunteers. Six normal healthy male beagle dogs (five to completion) received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by tandem mass spectrometry detection. A mechanistic absorption model was used to predict the in vivo dissolution and absorption characteristics of the oral formulations. Canine ciprofloxacin absorption was constrained to the duodenum/jejunum. This absorption window was far narrower than that seen in humans. Furthermore, while substantial within-individual variability in drug absorption was seen in human subjects, a greater magnitude of variability was observed in dogs. For three sets of data, a lag time in gastric emptying was necessary to improve the accuracy of model-generated in vivo blood level profile predictions. In addition to species-associated dissimilarities in drug solubilization due to human versus canine differences in gastrointestinal fluid compositions, the far more rapid intestinal transit time and potential segmental differences in drug absorption needed to be considered during human-canine extrapolation of oral drug and drug product performance. Through the use of mechanistic models, the data generated in the human and canine studies contributed insights into some aspects of the interspecies differences to be considered when extrapolating oral bioavailability/formulation effect data between dogs and humans.

  1. Manufacturing of diamond windows for synchrotron radiation

    SciTech Connect

    Schildkamp, W.; Nikitina, L.

    2012-09-15

    A new diamond window construction is presented and explicit manufacturing details are given. This window will increase the power dissipation by about a factor of 4 over present day state of the art windows to absorb 600 W of power. This power will be generated by in-vacuum undulators with the storage ring ALBA operating at a design current of 400 mA. Extensive finite element (FE) calculations are included to predict the windows behavior accompanied by explanations for the chosen boundary conditions. A simple linear model was used to cross-check the FE calculations.

  2. Scott Brothers Windows and Doors Information Sheet

    EPA Pesticide Factsheets

    Scott Brothers Windows and Doors (the Company) is located in Bridgeville, Pennsylvania. The settlement involves renovation activities conducted at property constructed prior to 1978, located in Pittsburgh, Pennsylvania.

  3. Performance tests of large thin vacuum windows

    SciTech Connect

    Hall Crannell

    2011-02-01

    Tests of thin composition vacuum windows of the type used for the Tagger in Hall B at the Thomas Jefferson National Accelerator Facility are described. Three different tests have been performed. These include: (1) measurement of the deformation and durability of a window under long term (>8 years) almost continuous vacuum load, (2) measurement of the deformation as a function of flexing of the window as it is cycled between vacuum and atmosphere, and (3) measurement of the relative diffusion rate of gas through a variety of thin window membranes.

  4. Window type: 2x3 fixed multipaned steel window flanked by 1x3 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Window type: 2x3 fixed multipaned steel window flanked by 1x3 multipaned steel casements. Concrete sill and spandrel also illustrated. Building 43, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  5. Development of cooled UV, visible and IR windows for quasicontinuous operation of the W7-X stellarator

    SciTech Connect

    Koenig, R.; Ogorodnikova, O.; Hildebrandt, D.; Grosser, K.; Sehren, C. von; Baldzuhn, J.; Burhenn, R.; Mertens, Ph.; Pospieszczyk, A.; Schweer, B.; Schmidt, H.; Klinger, T.

    2004-10-01

    The stellarator W7-X will be capable of running 30 min discharges. The expected continuous radiation power loads on plasma-facing optical components of 50 kW/m{sup 2} will be predominantly deposited in the form of short wavelength radiation (<60 nm) within the first millimeter of any window material. At such high heat loads actively water cooled windows are essential. The finite element-code ANSYS was used to calculate temperature and stress distributions across the windows for different window materials (CaF{sub 2}, MgF{sub 2}, quartz, ZnSe, sapphire), diameters, and thicknesses to explore any window design limitations resulting from the material properties of the different window substrates. First tests of a prototype water cooled window (coated with water-based colloidal graphite for effective IR absorption) in a specially designed vacuum test chamber equipped with a large surface vacuum compatible high power IR heater are being reported on. The temporal evolution of the temperature at different locations on the air side of the window and its surrounding structure is being monitored by several PT100 resistive thermometers while the spatial heat distribution across the cooled windows on their air and vacuum side is being measured with two IR cameras operating at 4 and 10 {mu}m.

  6. Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption.

    PubMed

    Nakamura, Toshimichi; Nakanishi, Takeo; Haruta, Tsunemitsu; Shirasaka, Yoshiyuki; Keogh, John P; Tamai, Ikumi

    2010-02-01

    Ipratropium bromide, an anticholinergic drug used for the treatment of asthma and chronic obstructive pulmonary disease, has low oral bioavailability, but systemic exposure, superior to oral administration, can be achieved by inhalation. Therefore, we investigated the pulmonary absorption mechanism of ipratropium using human bronchial epithelial BEAS-2B cells. [3H]Ipratropium uptake by BEAS-2B cells was temperature-dependent and saturable, with a K(m) value of 78.0 microM, suggesting involvement of carrier-mediated uptake. An RT-PCR study showed that organic cation/carnitine transporters OCTN1 and OCTN2 are expressed in BEAS-2B cells, but organic cation transporters (OCTs) are not. Uptake of [3H]ipratropium by HEK293 cells expressing OCTN1 (HEK293/OCTN1) and OCTN2 (HEK293/OCTN2) was significantly increased, compared with mock-transfected cells, and the estimated K(m) values were 444 microM and 53.0 microM, respectively. Finally, the contributions of OCTN1 and OCTN2 to ipratropium uptake were evaluated by measuring [3H]ipratropium uptake by BEAS-2B cells in which OCTN1 or OCTN2 gene expression had been silenced. Knock-down of OCTN1 or OCTN2 suppressed the uptake of [3H]ipratropium to 78.2% and 14.8% of that by control BEAS-2B cells, respectively. In addition, another anticholinergic, tiotropium, was also taken up by both HEK293/OCTN1 and HEK293/OCTN2 cells. Therefore, ipratropium and tiotropium are taken up primarily by OCTN2, and to a lesser extent by OCTN1, in bronchial epithelial cells. These findings are consistent with the pharmacological activity of the drugs after administration via inhalation.

  7. Performance of antireflecting coating-AlGaAs window layer coupling for terrestrial concentrator GaAs solar cells

    SciTech Connect

    Valle, C.A. del; Alcaraz, M.F.

    1997-09-01

    In this paper, the authors present the performance of optical coating systems coupled with AlGaAs window layers over GaAs solar cells. Single, double, and triple antireflecting coatings and window layers with constant and graded aluminum content are considered. Comparison between constant and graded window layers is established. To better represent reality, practical factors such as absorption of materials even for antireflecting coatings and the oxidation at window layer surface due to its high aluminum content are also included in the calculations. The design criteria to determine the optimum thickness of each layer is the achievement of maximum photogenerated current density. For this purpose and to account for terrestrial concentrators GaAs solar cells, the inclusion of direct terrestrial solar spectrum together with the internal spectral response of the device are taken into account. Finally, the best antireflecting coating/AlGaAs window layer couplings for different cases are presented.

  8. Optical Evaluation of DMDs with UV-Grade FS, Sapphire, MgF2 Windows and Reflectance of Bare Devices

    NASA Technical Reports Server (NTRS)

    Quijada, Manuel A.; Heap, Sara; Travinsky, Anton; Vorobiev, Dmitry; Ninkov, Zoran; Raisanen, Alan; Roberto, Massimo

    2016-01-01

    Digital Micro-mirror Devices (DMDs) have been identified as an alternative to microshutter arrays for space-based multi-object spectrometers (MOS). Specifically, the MOS at the heart of a proposed Galactic Evolution Spectroscopic Explorer (GESE) that uses the DMD as a reprogrammable slit mask. Unfortunately, the protective borosilicate windows limit the use of DMDs in the UV and IR regimes, where the glass has insufficient throughput. In this work, we present our efforts to replace standard DMD windows with custom windows made from UV-grade fused silica, Low Absorption Optical Sapphire (LAOS) and magnesium fluoride. We present reflectance measurements of the antireflection coated windows and a reflectance study of the DMDs active area (window removed). Furthermore, we investigated the long-term stability of the DMD reflectance and recoating device with fresh Al coatings.

  9. Glass-windowed ultrasound transducers.

    PubMed

    Yddal, Tostein; Gilja, Odd Helge; Cochran, Sandy; Postema, Michiel; Kotopoulis, Spiros

    2016-05-01

    In research and industrial processes, it is increasingly common practice to combine multiple measurement modalities. Nevertheless, experimental tools that allow the co-linear combination of optical and ultrasonic transmission have rarely been reported. The aim of this study was to develop and characterise a water-matched ultrasound transducer architecture using standard components, with a central optical window larger than 10 mm in diameter allowing for optical transmission. The window can be used to place illumination or imaging apparatus such as light guides, miniature cameras, or microscope objectives, simplifying experimental setups. Four design variations of a basic architecture were fabricated and characterised with the objective to assess whether the variations influence the acoustic output. The basic architecture consisted of a piezoelectric ring and a glass disc, with an aluminium casing. The designs differed in piezoelectric element dimensions: inner diameter, ID=10 mm, outer diameter, OD=25 mm, thickness, TH=4 mm or ID=20 mm, OD=40 mm, TH=5 mm; glass disc dimensions OD=20-50 mm, TH=2-4 mm; and details of assembly. The transducers' frequency responses were characterised using electrical impedance spectroscopy and pulse-echo measurements, the acoustic propagation pattern using acoustic pressure field scans, the acoustic power output using radiation force balance measurements, and the acoustic pressure using a needle hydrophone. Depending on the design and piezoelectric element dimensions, the resonance frequency was in the range 350-630 kHz, the -6 dB bandwidth was in the range 87-97%, acoustic output power exceeded 1 W, and acoustic pressure exceeded 1 MPa peak-to-peak. 3D stress simulations were performed to predict the isostatic pressure required to induce material failure and 4D acoustic simulations. The pressure simulations indicated that specific design variations could sustain isostatic pressures up to 4.8 MPa.The acoustic simulations were able to

  10. Thermal measurements of microwave transmitter feedhorn window

    NASA Technical Reports Server (NTRS)

    Perez, R. M.; Hoppe, D. J.

    1989-01-01

    Thermal measurements of microwave transmitter feedhorn windows were performed using an imaging infrared radiometer. The measurement technique is described and results are presented for windows made of 0.001-in. Kapton (trademark of Dupont Chemical Co.) and 0.1-in. HTP-6 (Space Shuttle tile material). Measured and calculated temperatures agree well.

  11. Humeral windows in revision total elbow arthroplasty.

    PubMed

    Peach, Chris A; Salama, Amir; Stanley, David

    2016-04-01

    The use of cortical windows for revision elbow arthroplasty has not previously been widely reported. Their use aids safe revision of a well fixed humeral prosthesis and can be used in the setting of dislocation, periprosthetic fracture or aseptic loosening of the ulnar component. We describe our technique and results of cortical windows in the distal humerus for revision elbow arthroplasty surgery.

  12. Tactical/Combat Engines Cetane Window Evaluation

    DTIC Science & Technology

    2013-01-31

    custom diesel fuels typically used in Homogeneous Charge Coupled Ignition ( HCCI ) research engines . These fuels are characterized by a very heavy...UNCLASSIFIED TACTICAL/COMBAT ENGINES CETANE WINDOW EVALUATION INTERIM REPORT TFLRF No. 436 by Gregory A. Hansen, Douglas Yost...report when no longer needed. Do not return it to the originator. UNCLASSIFIED UNCLASSIFIED TACTICAL/COMBAT ENGINES CETANE WINDOW

  13. Mouse Driven Window Graphics for Network Teaching.

    ERIC Educational Resources Information Center

    Makinson, G. J.; And Others

    Computer enhanced teaching of computational mathematics on a network system driving graphics terminals is being redeveloped for a mouse-driven, high resolution, windowed environment of a UNIX work station. Preservation of the features of networked access by heterogeneous terminals is provided by the use of the X Window environment. A dmonstrator…

  14. Simulations of lensless imaging in water window

    NASA Astrophysics Data System (ADS)

    Sveda, L.; Pina, L.

    2016-11-01

    A number of soft x-ray / water window laboratory sources is being developed by many groups including the group at CTU. This paper presents simulations and critical parameter estimates for lensless imaging using the laboratory sources, especially the capillary discharge source being developed by our group.1 Water window lensless imaging is demonstrated to be generally feasible with high repetition laboratory sources.

  15. Measure Guideline: Window Repair, Rehabilitation, and Replacement

    SciTech Connect

    Baker, P.

    2012-12-01

    This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

  16. Windows XP Operating System Security Analysis

    DTIC Science & Technology

    2002-09-01

    organizations. The purpose of this research is to determine if Windows XP, when used as a workstation operating system in domain- based networks, provides...... research is to determine if Windows XP, when used as a workstation operating system in domain based networks, provides adequate security policy

  17. Measured Rattle Threshold of Residential House Windows

    NASA Technical Reports Server (NTRS)

    Sizov, Natalia; Schultz, Troy; Hobbs, Christopher; Klos, Jacob

    2008-01-01

    Window rattle is a common indoor noise effect in houses exposed to low frequency noise from such sources as railroads, blast noise and sonic boom. Human perception of rattle can be negative that is a motivating factor of the current research effort to study sonic boom induced window rattle. A rattle study has been conducted on residential houses containing windows of different construction at a variety of geographic locations within the United States. Windows in these houses were excited by a portable, high-powered loudspeaker and enclosure specifically designed to be mounted on the house exterior to cover an entire window. Window vibration was measured with accelerometers placed on different window components. Reference microphones were also placed inside the house and inside of the loudspeaker box. Swept sine excitation was used to identify the vibration threshold at which the response of the structure becomes non-linear and begins to rattle. Initial results from this study are presented and discussed. Future efforts will continue to explore the rattle occurrence in windows of residential houses exposed to sonic booms.

  18. Transport of gemifloxacin, a 4th generation quinolone antibiotic, in the Caco-2 and engineered MDCKII cells, and potential involvement of efflux transporters in the intestinal absorption of the drug.

    PubMed

    Jin, Hyo-Eon; Song, Boran; Kim, Sang-Bum; Shim, Won-Sik; Kim, Dae-Duk; Chong, Saeho; Chung, Suk-Jae; Shim, Chang-Koo

    2013-04-01

    The oral (po) bioavailability of gemifloxacin mesylate in rats and its possible association with efflux transporters was investigated. The apparent permeabilities (Papp) of gemifloxacin across the Caco-2 cell monolayer were 1.20 ± 0.09 × 10(-5) cm/s for apical to basal (absorptive) transport, and 2.13 ± 0.6 × 10(-5) cm/s for basal to apical (secretory) transport for a 5-500 μM concentration range, suggesting the involvement of a carrier-mediated efflux in the secretory transport. The secretory transport in Caco-2 cells was significantly decreased by MRP2 (MK571) and BCRP (Ko143) inhibitors. The secretory transport was distinct in MDCKII/P-gp, MDCKII/MRP2 and MDCKII/BCRP cells, and the affinity was highest for MRP2, followed by BCRP and P-gp. The efflux was significantly decreased by verapamil and Ko143, but not significantly by MK571. The comparative po bioavailability in rats was increased by the preadministration of Ko143 (four-fold), MK571 (two-fold) and verapamil (two-fold). Efflux transporters appeared to significantly limit the bioavailability of gemifloxacin in rats, suggesting their possible contribution to the low bioavailability of the drug in the human (70%).

  19. A monolithic thin film electrochromic window

    SciTech Connect

    Goldner, R.B.; Arntz, F.O.; Berera, G.; Haas, T.E.; Wong, K.K.; Wei, G.; Yu, P.C.

    1991-12-31

    Three closely related thin film solid state ionic devices that are potentially important for applications are: electrochromic smart windows, high energy density thin film rechargeable batteries, and thin film electrochemical sensors. Each usually has at least on mixed ion/electron conductor, an electron-blocking ion conductor, and an ion-blocking electron conductor, and many of the technical issues associated with thin film solid state ionics are common to all three devices. Since the electrochromic window has the added technical requirement of electrically-controlled optical modulation, (over the solar spectrum), and since research at the authors` institution has focused primarily on the window structure, this paper will address the electrochromic window, and particularly a monolithic variable reflectivity electrochromic window, as an illustrative example of some of the challenges and opportunities that are confronting the thin film solid state ionics community. 33 refs.

  20. A monolithic thin film electrochromic window

    SciTech Connect

    Goldner, R.B.; Arntz, F.O.; Berera, G.; Haas, T.E.; Wong, K.K. . Electro-Optics Technology Center); Wei, G. ); Yu, P.C. )

    1991-01-01

    Three closely related thin film solid state ionic devices that are potentially important for applications are: electrochromic smart windows, high energy density thin film rechargeable batteries, and thin film electrochemical sensors. Each usually has at least on mixed ion/electron conductor, an electron-blocking ion conductor, and an ion-blocking electron conductor, and many of the technical issues associated with thin film solid state ionics are common to all three devices. Since the electrochromic window has the added technical requirement of electrically-controlled optical modulation, (over the solar spectrum), and since research at the authors' institution has focused primarily on the window structure, this paper will address the electrochromic window, and particularly a monolithic variable reflectivity electrochromic window, as an illustrative example of some of the challenges and opportunities that are confronting the thin film solid state ionics community. 33 refs.

  1. Compact UHV valve with field replaceable windows

    SciTech Connect

    Johnson, E.D. ); Freeman, J. ); Powell, F. )

    1992-01-01

    There are many applications in synchrotron radiation research where window valves can be usefully employed. Examples include gas cells for monochromator calibration, filters for high-order light rejection, and as vacuum isolation elements between machine and experimental vacua. Often these devices are fairly expensive, and have only fixed (i.e., nonremovable) windows. The development of a new type of seal technology by VAT for their series 01 valves provides a gate surface which is free from obstructions due to internal mechanical elements. This feature allows a threaded recess to be machined into the gate to receive a removable window frame which can carry standard size Luxel thin-film windows. The combination of these features results in a DN 40 (2.75-in. conflat flange) valve which provides a clear aperture of 21-mm diameter for the window material.

  2. Compact UHV valve with field replaceable windows

    SciTech Connect

    Johnson, E.D. ); Freeman, J. ); Powell, F. )

    1991-01-01

    There are many applications in synchrotron radiation research where window valves can be usefully employed. Examples include gas cells for monochromator calibration, filters for high order light rejection, and as vacuum isolation elements between machine and experimental vacua. Often these devices are fairly expensive, and have only fixed (ie non-removable) windows. The development of a new type of seal technology by VAT for their series 01 valves provides a gate surface which is free from obstructions due to internal mechanical elements. This feature allows a threaded recess to be machined into the gate to receive a removable window frame which can carry standard size Luxel thin film windows. The combination of these features results in a DN 40 (2.75in. conflat flange) valve which provides a clear aperture of 21mm diameter for the window material. 8 refs., 2 figs.

  3. THERM 5 / WINDOW 5 NFRC simulation manual

    SciTech Connect

    Mitchell, Robin; Kohler, Christian; Arasteh, Dariush; Carmody, John; Huizenga, Charlie; Curcija, Dragan

    2003-06-01

    This document, the ''THERM 5/WINDOW 5 NFRC Simulation Manual', discusses how to use the THERM and WINDOW programs to model products for NFRC certified simulations and assumes that the user is already familiar with those programs. In order to learn how to use these programs, it is necessary to become familiar with the material in both the ''THERM User's Manual'' and the ''WINDOW User's Manual''. In general, this manual references the User's Manuals rather than repeating the information. If there is a conflict between either of the User Manual and this ''THERM 5/''WINDOW 5 NFRC Simulation Manual'', the ''THERM 5/WINDOW 5 NFRC Simulation Manual'' takes precedence. In addition, if this manual is in conflict with any NFRC standards, the standards take precedence. For example, if samples in this manual do not follow the current taping and testing NFRC standards, the standards not the samples in this manual, take precedence.

  4. Least Squares Moving-Window Spectral Analysis.

    PubMed

    Lee, Young Jong

    2017-01-01

    Least squares regression is proposed as a moving-windows method for analysis of a series of spectra acquired as a function of external perturbation. The least squares moving-window (LSMW) method can be considered an extended form of the Savitzky-Golay differentiation for nonuniform perturbation spacing. LSMW is characterized in terms of moving-window size, perturbation spacing type, and intensity noise. Simulation results from LSMW are compared with results from other numerical differentiation methods, such as single-interval differentiation, autocorrelation moving-window, and perturbation correlation moving-window methods. It is demonstrated that this simple LSMW method can be useful for quantitative analysis of nonuniformly spaced spectral data with high frequency noise.

  5. Holography of the conformal window

    NASA Astrophysics Data System (ADS)

    Alvares, Raul; Evans, Nick; Kim, Keun-Young

    2012-07-01

    Inspired by the model of Jarvinen and Kiritsis, we present a simple holographic model for the onset of chiral symmetry breaking at the edge of the conformal window in QCD in the Veneziano limit. Our most naive model enforces the QCD two-loop running coupling on a D3/D7 holographic brane system. The mass of the holographic field, describing the chiral condensate in the model, is driven below the Breitenlohner-Freedman bound when the running is sufficiently strong, triggering chiral symmetry breaking for Nf/Nc<2.9. This model though contains too great a remnant of supersymmetry and does not correctly encode the perturbative anomalous dimensions of QCD. In a second model we impose the QCD anomalous dimension result and find chiral symmetry breaking sets in for Nf/Nc=4 at a Berezinsky-Kosterlitz-Thouless-type phase transition. In this case the transition is triggered when the anomalous dimension of the mass operator γm=1.

  6. Templated fabrication of hollow nanospheres with 'windows' of accurate size and tunable number.

    PubMed

    Xie, Duan; Hou, Yidong; Su, Yarong; Gao, Fuhua; Du, Jinglei

    2015-01-01

    The 'windows' or 'doors' on the surface of a closed hollow structure can enable the exchange of material and information between the interior and exterior of one hollow sphere or between two hollow spheres, and this information or material exchange can also be controlled through altering the window' size. Thus, it is very interesting and important to achieve the fabrication and adjustment of the 'windows' or 'doors' on the surface of a closed hollow structure. In this paper, we propose a new method based on the temple-assisted deposition method to achieve the fabrication of hollow spheres with windows of accurate size and number. Through precisely controlling of deposition parameters (i.e., deposition angle and number), hollow spheres with windows of total size from 0% to 50% and number from 1 to 6 have been successfully achieved. A geometrical model has been developed for the morphology simulation and size calculation of the windows, and the simulation results meet well with the experiment. This model will greatly improve the convenience and efficiency of this temple-assisted deposition method. In addition, these hollow spheres with desired windows also can be dispersed into liquid or arranged regularly on any desired substrate. These advantages will maximize their applications in many fields, such as drug transport and nano-research container.

  7. Photodetachment neutralizer development: Laser window design study: Volume 1, Summary: Final report

    SciTech Connect

    Not Available

    1984-09-30

    Photodetachment neutralization (PDN) has been proposed as a major improvement to the gas cell neutralization utilized on current neutral beam heating systems for magnetic containment fusion devices. This PDN system will use a Chemical Oxygen Iodine Laser (COIL) to produce a light beam with photons of a near optimal wavelength which can be reflected back and forth across the path of the ion beam to create the necessary high density light ''cloud'' required for the photodetachment process. In a fusion device the neutral beam goes directly into the process vacuum chamber and therefore the oxygen iodine gas mixture in the laser must be isolated by a window from the neutral beam channel without loss of too much light or leakage of miniscule quantities of laser gas. The aerodynamic windows that have traditionally been used with chemical lasers are viewed as undesirable for the fusion application where any contamination of the fusion vacuum chamber by laser gas would be a big problem. It was concluded that the technological issues were uncertain enough that a verification by designing, fabricating, and testing of a demonstration window would be required before feasibility of such a window could be considered certain. The statement of work defined for this study consisted of two tasks: determination of the absorption characteristics of the proposed sapphire window material and the fluorocarbon coolant, and design and analysis of the proposed double disk heat exchanger window and demonstration test hardware.

  8. Transmission in near-infrared optical windows for deep brain imaging.

    PubMed

    Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I.

  9. Double window configuration as a low cost microwave waveguide window for plasma applications

    SciTech Connect

    Baskaran, R.

    1997-12-01

    Waveguide windows are major components of a transmission line used in microwave plasma devices. The function of the waveguide window is to provide vacuum isolation of the source side from the plasma chamber while transmitting microwaves with minimum attenuation. Commonly a single thin dielectric plate is sandwiched between a choke type flange and a flat flange and is used as a waveguide window. To arrive at a better window configuration in terms of the low power reflection coefficient, the voltage standing wave ratio calculation is carried out for different window configurations (single window and double window) and for various window thicknesses. It is found that the power reflection is the minimum in the case of double window configuration. The minimum power reflection is as low as 0.8{percent} for a combination of alumina and a quartz plate each of 1 cm thickness in the double window configuration. Also, it is more advantageous to use radial microwave coupling than axial coupling in order to increase the life time of the microwave waveguide window. {copyright} {ital 1997 American Institute of Physics.}

  10. Old practices, new windows: reflections on a communications skills innovation.

    PubMed

    Cantillon, Peter

    2017-03-01

    Most of the great innovations in communication skills education, from Balint's concept of the 'doctor as drug' to the Calgary Cambridge conceptualisation of the consultation, were founded in general practice. It can be argued however, that there has been a hiatus in the development of new approaches to analysing the consultation since the mid-1990s. It is most welcome therefore that in this issue of the journal two papers are presented that describe and evaluate a novel approach to consultation analysis entitled 'the windows method'. Building on the more structured approaches that preceded it, the windows method offers some genuine innovations in terms of its emphasis on emotional knowledge and the manner in which it addresses many of the potential deficiencies in feedback practice associated with older methods. The new approach is very much in step with current thinking about emotional development and the establishment of appropriate environments for feedback. The windows method has the potential to breathe fresh life into old and well-established communication skills education practices.

  11. Window Insulation: How to Sort Through the Options.

    ERIC Educational Resources Information Center

    Miller, Barbara

    This two-part report explores the efforts of businesses and individuals to improve the thermal performance of windows. Part I discusses the basics of what makes a window product insulate or save energy. Topic areas addressed include saving energy lost through windows, key components of window insulation, three basic types of window insulation,…

  12. Efficient Adjustable Reflectivity Smart Window

    SciTech Connect

    D. Morgan Tench

    2005-12-01

    This project addressed the key technical issues for development of an efficient smart window based on reversible electrochemical transfer of silver between a mirror electrode and a localized counter electrode. Effort to provide uniform switching over large areas focused on use of a resistive transparent electrode innerlayer to increase the interelectrode resistance. An effective edge seal was developed in collaboration with adhesive suppliers and an electrochromic device manufacturer. Work to provide a manufacturable counter electrode focused on fabricating a dot matrix electrode without photolithography by electrodeposition of Pt nuclei on inherent active sites on a transparent oxide conductor. An alternative counter electrode based on a conducting polymer and an ionic liquid electrolyte was also investigated. Work in all of these areas was successful. Sputtered large-bandgap oxide innerlayers sandwiched between conductive indium tin oxide (ITO) layers were shown to provide sufficient cross-layer resistance (>300 ohm/cm{sup 2}) without significantly affecting the electrochemical properties of the ITO overlayer. Two edge seal epoxies, one procured from an epoxy manufacturer and one provided by an electrochromic device manufacturer in finished seals, were shown to be effective barriers against oxygen intrusion up to 80 C. The optimum density of nuclei for the dot matrix counter electrode was attained without use of photolithography by electrodeposition from a commercial alkaline platinum plating bath. Silver loss issues for cells with dot matrix electrodes were successfully addressed by purifying the electrolyte and adjusting the cell cycling parameters. More than 30K cycles were demonstrated for a REM cell (30-cm square) with a dot matrix counter electrode. Larger cells (30-cm square) were successfully fabricated but could not be cycled since the nucleation layers (provided by an outside supplier) were defective so that mirror deposits could not be produced.

  13. Thermal runaway in semiconductor laser windows.

    PubMed

    Johnson, R L; O'Keefe, J D

    1972-12-01

    A small perturbation model is used to obtain analytical expressions for the critical or runaway power density for laser windows constructed of semiconductor materials. These equations are used to compute the critical power density for several realistic window installations taking account of the finite value of realizable convection cooling coefficients. Computations were prepared for silicon transmitting 4 .0-micro. radiation and for germanium at 10.6 micro. In this way it is shown that power densities are principally limited by the effectiveness of cooling from the face of the window, that is, the surface perpendicular to the laser beam. Since convection cooling coefficients are small the transmission of high power densities through semiconductor windows is therefore contingent upon finding more effective means to cool the window from the face. Finally, a simplified calculation was made in an attempt to account for nonuniformity of the incident laser beam. a given window, but not severely. The results show the onuniformity reduces the runaway power for a given window, but not severely.

  14. Focal plane scanner with reciprocating spatial window

    NASA Technical Reports Server (NTRS)

    Mao, Chengye (Inventor)

    2000-01-01

    A focal plane scanner having a front objective lens, a spatial window for selectively passing a portion of the image therethrough, and a CCD array for receiving the passed portion of the image. All embodiments have a common feature whereby the spatial window and CCD array are mounted for simultaneous relative reciprocating movement with respect to the front objective lens, and the spatial window is mounted within the focal plane of the front objective. In a first embodiment, the spatial window is a slit and the CCD array is one-dimensional, and successive rows of the image in the focal plane of the front objective lens are passed to the CCD array by an image relay lens interposed between the slit and the CCD array. In a second embodiment, the spatial window is a slit, the CCD array is two-dimensional, and a prism-grating-prism optical spectrometer is interposed between the slit and the CCD array so as to cause the scanned row to be split into a plurality of spectral separations onto the CCD array. In a third embodiment, the CCD array is two-dimensional and the spatial window is a rectangular linear variable filter (LVF) window, so as to cause the scanned rows impinging on the LVF to be bandpass filtered into spectral components onto the CCD array through an image relay lens interposed between the LVF and the CCD array.

  15. Plasmonic thin films for application in improved chromogenic windows

    NASA Astrophysics Data System (ADS)

    Niklasson, Gunnar A.; Lansåker, Pia C.; Li, Shu-Yi; Granqvist, Claes G.

    2016-02-01

    Nanocomposites consisting of noble metal nanoparticles in a transparent matrix exhibit plasmonic absorption in the visible wavelength range, and conducting oxide nanoparticles display a localized plasma absorption in the near infrared. The optical properties of nanocomposites are commonly modelled by effective medium theories, which describe the effective dielectric function of the composite using as input the dielectric functions of the constituents and their respective volume fractions. Plasmonic effects can be exploited in the design of energy-efficient windows in order to obtain improved performance. Electrochromic coatings that switch in the near infrared make use of the modulation of the plasma absorption of oxide nanoparticles due to charge density modulation induced by an external voltage. Plasmonic thermochromic switching in the near infrared has the potential to be significantly larger than in the case of a thin film. Very thin noble metal films are an interesting alternative to conducting oxides as transparent contacts to electrochromic devices. However, in this latter case plasmonic effects are to be avoided rather than exploited.

  16. Oral anticancer drugs: mechanisms of low bioavailability and strategies for improvement.

    PubMed

    Stuurman, Frederik E; Nuijen, Bastiaan; Beijnen, Jos H; Schellens, Jan H M

    2013-06-01

    The use of oral anticancer drugs has increased during the last decade, because of patient preference, lower costs, proven efficacy, lack of infusion-related inconveniences, and the opportunity to develop chronic treatment regimens. Oral administration of anticancer drugs is, however, often hampered by limited bioavailability of the drug, which is associated with a wide variability. Since most anticancer drugs have a narrow therapeutic window and are dosed at or close to the maximum tolerated dose, a wide variability in the bioavailability can have a negative impact on treatment outcome. This review discusses mechanisms of low bioavailability of oral anticancer drugs and strategies for improvement. The extent of oral bioavailability depends on many factors, including release of the drug from the pharmaceutical dosage form, a drug's stability in the gastrointestinal tract, factors affecting dissolution, the rate of passage through the gut wall, and the pre-systemic metabolism in the gut wall and liver. These factors are divided into pharmaceutical limitations, physiological endogenous limitations, and patient-specific limitations. There are several strategies to reduce or overcome these limitations. First, pharmaceutical adjustment of the formulation or the physicochemical characteristics of the drug can improve the dissolution rate and absorption. Second, pharmacological interventions by combining the drug with inhibitors of transporter proteins and/or pre-systemic metabolizing enzymes can overcome the physiological endogenous limitations. Third, chemical modification of a drug by synthesis of a derivative, salt form, or prodrug could enhance the bioavailability by improving the absorption and bypassing physiological endogenous limitations. Although the bioavailability can be enhanced by various strategies, the development of novel oral products with low solubility or cell membrane permeability remains cumbersome and is often unsuccessful. The main reasons are

  17. Optimal spectral windows for microwave diversity imaging

    NASA Technical Reports Server (NTRS)

    Farhat, Nabil H.; Bai, Baocheng

    1991-01-01

    Tomographic microwave diversity imaging is analyzed using linear system theory concepts, and optimal spectral windows for data acquisition are obtained either by considering window position in the spectral domain or by using simulated annealing to find an optimal phase weighting of the object frequency response samples collected over the specified spectral window. This study provides a means of microwave image formation that is applicable under general assumptions. Results of numerical simulations and representative images reconstructed from realistic experimental microwave scattering data are given, demonstrating that the proposed approach is superior to previous image reconstruction methods.

  18. Apollo experience report: Spacecraft structural windows

    NASA Technical Reports Server (NTRS)

    Pigg, O. E.; Weiss, S. P.

    1973-01-01

    The window structural design and verification experience is presented for the Apollo command and lunar modules. This report presents window design philosophy, design criteria, hardware description, and qualification and acceptance test programs and discusses the problems encountered and solutions developed in these areas. The structural characteristics of glass are not generally well understood by designers. The optics and instrument glass covers were not considered to be structural components and thus were not normally subjected to the design, qualification, and acceptance standards necessary to preclude failures. These two factors contributed significantly to window problems on both Apollo spacecraft.

  19. 4. NORTH ELEVATION, SHOWING BROKEN PEDIMENTED GABLE, ARCHED WINDOW IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. NORTH ELEVATION, SHOWING BROKEN PEDIMENTED GABLE, ARCHED WINDOW IN GABLE, AND SEGMENTALLY ARCHED WINDOW HEADS ON SECOND FLOOR WINDOWS - Jacob R. Fisher House, High Street, Oldwick, Hunterdon County, NJ

  20. DETAIL VIEW, WEST VENETIAN WINDOW IN SOUTH WALL. (NOTE THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW, WEST VENETIAN WINDOW IN SOUTH WALL. (NOTE THE IRON BARS ON THE CELLAR WINDOW BELOW. THIS WINDOW LETS ONTO WHAT WAS LIKELY THE ESTATE OFFICE DURING THE HAMILTONIAN RESIDENCY - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  1. Field Evaluation of Low-E Storm Windows

    SciTech Connect

    Drumheller, S. Craig; Kohler, Christian; Minen, Stefanie

    2007-07-11

    A field evaluation comparing the performance of low emittance (low-e) storm windows with both standard clear storm windows and no storm windows was performed in a cold climate. Six homes with single-pane windows were monitored over the period of one heating season. The homes were monitored with no storm windows and with new storm windows. The storm windows installed on four of the six homes included a hard coat, pyrolitic, low-e coating while the storm windows for the other two homeshad traditional clear glass. Overall heating load reduction due to the storm windows was 13percent with the clear glass and 21percent with the low-e windows. Simple paybacks for the addition of the storm windows were 10 years for the clear glass and 4.5 years forthe low-e storm windows.

  2. DETAIL OF GROUND, MEZZANINE, AND FIRST FLOOW WINDOW OPENINGS AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF GROUND, MEZZANINE, AND FIRST FLOOW WINDOW OPENINGS AT CORNER OF CLAY AND 15TH STREETS. WINDOWS AND WINDOW FRAMES REMOVED - John Breuner & Company Building, 1515 Clay Street, Oakland, Alameda County, CA

  3. Analytical stress modeling of high-energy laser windows: Application to fusion-cast calcium fluoride windows

    NASA Astrophysics Data System (ADS)

    Klein, Claude A.

    2005-08-01

    The performance of a laser-window material must be assessed not only in terms of its ability to transmit high-power beams without generating undue optical distortion but also in terms of the constraints imposed by stress-related failure modes. In operational use, the stress field images the superposition of stresses originating from the mechanical load created by the pressure differential and the thermal load created by the laser beam. Here, we provide the tools to carry out an analysis of both pressure- and beam-induced stresses, and illustrate the procedure in the context of assessing the performance of a "model" window made of fusion-cast CaF2. The analysis assumes (a) operation on a time scale such that lateral heat diffusion can be ignored, and (b) cylindrically symmetric Gaussian beam shapes, which permit straightforward calculations of stress distributions that should be representative of worst case situations. Pressure-induced stresses strongly depend on the window's aspect ratio, which suggests increasing the thickness to minimize the stress, but considerations relating to the optical performance require minimum allowable thicknesses based on a Weibull statistical analysis of the fracture probability. Beam-induced stresses are best evaluated in terms of (a) thickness-averaged radial and azimuthal stresses, which increase linearly with exposure time and depend on radial distances through the truncation parameter, and (b) across-the-thickness stress deviations relative to the average stress, which are caused by surface absorption and reach steady-state configurations on a time scale much shorter than the characteristic time for lateral heat transport. The average stress is always compressive and equibiaxial in the central region of the window, but its azimuthal component turns tensile in the rim region, thus threatening the structural integrity through brittle fracture. In addition, the coating-induced stress results in on-axis surface compressions that may

  4. Translational nanomedicine--through the therapeutic window.

    PubMed

    Pierce, Robin L

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic effect, a second definition of the therapeutic window refers to the often narrow temporal window in which a therapeutic effect can be obtained. Expanding the second definition to explicitly include the spatial dimension, this article explores aspects of the therapeutic spaces created by nanomedicine that shift the traditional dimensions of symptom, sign and pathology. This article analyzes three aspects of the therapeutic window in nanomedicine - temporal, spatial and manner of construction and their impact on the dimensions of modern medicine.

  5. Opening a window on the universe

    NASA Astrophysics Data System (ADS)

    Dutson, Kate

    2015-04-01

    The Cherenkov Telescope Array will revolutionize ground-based gamma-ray astronomy, explains Kate Dutson, extending our electromagnetic window on to the universe to include the highest-energy photons ever detected.

  6. NREL Electrochromic Window Research Wins Award

    ScienceCinema

    None

    2016-07-12

    Winners of the CO-LABS Governor's Award for High-Impact Research in Energy Efficiency, Dr. Satyen Deb at the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) discovered that a small electrical charge can change the opacity of tungsten oxide from clear to tinted. He, Dr. Dane Gillaspie, and their fellow scientists at NREL then applied this knowledge to develop and transfer the technologies required to construct an electrochromic window, which can switch between clear and heavily tinted states. Electrochromic windows allow natural light in while adding tint to reduce summer heat and glare, and going clear to allow sunlight through in the winter. Broad adaptation of these windows could reduce US total energy use by four percent and reduce building cooling loads by 20%, much of this during expensive peak hours. Windows based on these discoveries are now being installed worldwide.

  7. Upstate Windows and Exteriors Information Sheet

    EPA Pesticide Factsheets

    Upstate Windows and Exteriors (the Company) is located in Greenville, South Carolina. The settlement involves renovation activities conducted at properties constructed prior to 1978, located in Greenville and Easley, South Carolina.

  8. The Window Men, Inc. Information Sheet

    EPA Pesticide Factsheets

    The Window Men, Inc. (the Company) is located in Lynchburg, Virginia. The settlement involves renovation activities conducted at properties constructed prior to 1978, located in Lynchburg and Amherst, Virginia.

  9. Clooten Siding & Window, Inc. Information Sheet

    EPA Pesticide Factsheets

    Clooten Siding & Window, Inc. (the Company) is located in Bismarck, North Dakota. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Bismarck, North Dakota.

  10. Development of Deicing Techniques for Dielectric Windows.

    DTIC Science & Technology

    1975-08-01

    greater than 70%, and a sheet resistance of 160 ohms/square is described. Also included is a thermo-optical analysis of conductive films and patterns for zinc sulfide, zinc selenide, and zinc sulfo-selenide windows.

  11. Custom Windows: The Choice Is Crystal Clear.

    ERIC Educational Resources Information Center

    Wetzel, Steve

    1999-01-01

    Discusses the 12 services schools should request of their custom window manufacturer. Services requested are designed to make a viable partnership between the school and manufacturer that satisfies building aesthetics, enhances performance needs, and controls risk. (GR)

  12. Food and Drug Interactions.

    PubMed

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  13. Holographic window for solar power generation

    NASA Astrophysics Data System (ADS)

    Kasezawa, Toshihiro; Horimai, Hideyoshi; Tabuchi, Hiroshi; Shimura, Tsutomu

    2016-12-01

    A new photovoltaic generation unit based on the application of holographic technologies called a Holo-Window is proposed in this work. The basic principle and the optical configuration used for the basic experimental unit are described. Suitable fabrication technology for a hologram with the broadband spectrum required to provide the appropriate sunlight capture capability is then discussed. Finally, a laboratory-prototype Holo-Window unit was developed and its performance was evaluated.

  14. Laser Window Surface Finishing and Coating Science

    DTIC Science & Technology

    1975-07-01

    IKlf il fie. r . *ttt\\ mil nlrol’ly h\\ lllm k Itumhvr ■ LasLr windows. Surface finishing, Thin films , Antireflection coatings , 10.6...Zuccaro) During the course of our program it is our objective to prepare antireflection (AR) film coatings for candidate infrared laser window...antireflection coatings under UHV conditions and to compare; these films with (.host- prepared under ordinary vacuum conditions. a. Experimental Results

  15. Thermal effects in Cs DPAL and alkali cell window damage

    NASA Astrophysics Data System (ADS)

    Zhdanov, B. V.; Rotondaro, M. D.; Shaffer, M. K.; Knize, R. J.

    2016-10-01

    Experiments on power scaling of Diode Pumped Alkali Lasers (DPALs) revealed some limiting parasitic effects such as alkali cell windows and gain medium contamination and damage, output power degradation in time and others causing lasing efficiency decrease or even stop lasing1 . These problems can be connected with thermal effects, ionization, chemical interactions between the gain medium components and alkali cells materials. Study of all these and, possibly, other limiting effects and ways to mitigate them is very important for high power DPAL development. In this talk we present results of our experiments on temperature measurements in the gain medium of operating Cs DPAL at different pump power levels in the range from lasing threshold to the levels causing damage of the alkali cell windows. For precise contactless in situ temperature measurements, we used an interferometric technique, developed in our lab2 . In these experiments we demonstrated that damage of the lasing alkali cell starts in the bulk with thermal breakdown of the hydrocarbon buffer gas. The degradation processes start at definite critical temperatures of the gain medium, different for each mixture of buffer gas. At this critical temperature, the hydrocarbon and the excited alkali metal begin to react producing the characteristic black soot and, possibly, some other chemical compounds, which both harm the laser performance and significantly increase the harmful heat deposition within the laser medium. This soot, being highly absorptive, is catastrophically heated to very high temperatures that visually observed as bulk burning. This process quickly spreads to the cell windows and causes their damage. As a result, the whole cell is also contaminated with products of chemical reactions.

  16. Rugged spinel windows and optics for harsh environments

    NASA Astrophysics Data System (ADS)

    Bayya, Shyam; Villalobos, Guillermo; Kim, Woohong; Busse, Lynda; Sanghera, Jasbinder; Aggarwal, Ishwar

    2013-05-01

    Spinel is a rugged ceramic transparent from ultraviolet to midwave infrared (0.18 - 5.5 μm) wavelengths. It has the best transmission from 4-5 μm among the competing materials ALON and sapphire with comparable mechanical properties. We have developed low absorption loss spinel as an exit window aperture for High Energy Laser systems. We demonstrated that spinel possesses excellent thermo-optical characteristics required for the High Energy Laser systems and at the same time it can provide the necessary ruggedness desired for the realistic and harsh battlefield environment. We have demonstrated through testing that spinel can withstand very adverse conditions of rain, sand storms and salt fog conditions without any change in its optical performance. We have also developed rugged anti-reflective coatings and anti-reflective surface structures to maintain high optical transmission in adverse environment.

  17. Electrochromic sun control coverings for windows

    SciTech Connect

    Benson, D K; Tracy, C E

    1990-04-01

    The 2 billion square meters (m{sup 2}) of building windows in the United States cause a national energy drain almost as large as the energy supply of the Alaskan oil pipeline. Unlike the pipeline, the drain of energy through windows will continue well into the 21st century. A part of this energy drain is due to unwanted sun gain through windows. This is a problem throughout the country in commercial buildings because they generally require air conditioning even in cold climates. New commercial windows create an additional 1600 MW demand for peak electric power in the United States each year. Sun control films, widely used in new windows and as retrofits to old windows, help to mitigate this problem. However, conventional, static solar control films also block sunlight when it is wanted for warmth and daylighting. New electrochromic, switchable, sun-gain-control films now under development will provide more nearly optimal and automatic sun control for added comfort, decreased building operating expense, and greater energy saving. Switchable, electrochromic films can be deposited on polymers at high speeds by plasma enhanced chemical vapor deposition (PECVD) in a process that may be suitable for roll coating. This paper describes the electrochromic coatings and the PECVD processes, and speculates about their adaptability to high-speed roll coating. 8 refs., 3 figs.

  18. Dust adhesion on Viking lander camera window

    NASA Technical Reports Server (NTRS)

    Singh, J. J.

    1978-01-01

    Studies of dust impingement on a duplicate Viking Lander camera window indicated the possibility of window obscuration after several days of exposure even at low dust concentration levels. As a result the following corrective measures were recommended: (1) The clearance between the housing surface and the camera post should be eliminated by using an appropriately designed plastic skirt: (2) The three horizontal ledges below the window inside the cavity act as bases for pile-up of dust that slides down the window surface; they should be replaced by a single inclined plane down which the dust will slide and fall out on the ground: (3) Adhered dust on the window surface can be removed by high pressure CO2 jets directed down against the window; the amount of CO2 gas needed for the entire mission can be carried in a 3 1/2-inch diameter sphere equipped with a remotely programable valve. These measures were incorporated in the design of the lander camera system. The continued high quality of photographs transmitted from the Viking spacecraft several months after landing attests to their effectiveness.

  19. Scale up of large ALON windows

    NASA Astrophysics Data System (ADS)

    Goldman, Lee M.; Balasubramanian, Sreeram; Kashalikar, Uday; Foti, Robyn; Sastri, Suri

    2013-06-01

    Aluminum Oxynitride (ALON® Optical Ceramic) combines broadband transparency with excellent mechanical properties. ALON's cubic structure means that it is transparent in its polycrystalline form, allowing it to be manufactured by conventional powder processing techniques. Surmet has established a robust manufacturing process, beginning with synthesis of ALON® powder, continuing through forming/heat treatment of blanks, and ending with optical fabrication of ALON® windows. Surmet has made significant progress in our production capability in recent years. Additional scale up of Surmet's manufacturing capability, for larger sizes and higher quantities, is currently underway. ALON® transparent armor represents the state of the art in protection against armor piercing threats, offering a factor of two in weight and thickness savings over conventional glass laminates. Tiled and monolithic windows have been successfully produced and tested against a range of threats. Large ALON® window are also of interest to a range of visible to Mid-Wave Infra-Red (MWIR) sensor applications. These applications often have stressing imaging requirements which in turn require that these large windows have optical characteristics including excellent homogeneity of index of refraction and very low stress birefringence. Surmet is currently scaling up its production facility to be able to make and deliver ALON® monolithic windows as large as ~19x36-in. Additionally, Surmet has plans to scale up to windows ~3ftx3ft in size in the coming years. Recent results with scale up and characterization of the resulting blanks will be presented.

  20. Millimeter-wave dielectric properties of infrared window materials

    NASA Astrophysics Data System (ADS)

    Ho, W. W.

    1987-01-01

    The millimeter-wave dielectric properties of a series of IR window materials were determined over the temperature range 23-1000 C. Materials studied included Al2O3, ZnS, ZnSe, aluminum oxynitride (ALON), and magnesium-spinel (MgAl2O4). These materials all exhibited fairly high millimeter-wave dielectric constants, but with essentially negligible room-temperature losses for most applications. However, both the dielectric constant and loss tangent increase significantly with increasing temperatures. The increases in dielectric constant with temperature can be analyzed in terms of a macroscopic dielectric virial expansion model, and are primarily due to the effective increase in volume for each polarizable unit of the material. Consequently, a strategy to overcome this degradation would be to search for new materials or composite structures with low thermal expansion coefficients. The observed millimeter-wave loss properties are characteristic of contributions from intergranular impurities and show an onset of increased absorption at about 500. However, even at 1000 C, typical loss tangents are still below 0.05, and should be acceptable in most millimeter-wave window applications for reasonable thicknesses.

  1. BIPV-Powered Smart Windows Utilizing Photovoltaic and Electrochromic Devices

    PubMed Central

    Ma, Rong-Hua; Chen, Yu-Chia

    2012-01-01

    A BIPV-powered smart window comprising a building-integrated photovoltaic (BIPV) panel and an all-solid-state electrochromic (EC) stack is proposed. In the proposed device, the output voltage of the BIPV panel varies in accordance with the intensity of the incident light and is modulated in such a way as to generate the EC stack voltage required to maintain the indoor illuminance within a specified range. Two different EC stacks are fabricated and characterized, namely one stack comprising ITO/WO3/Ta2O5/ITO and one stack comprising ITO/WO3/lithium-polymer electrolyte/ITO. It is shown that of the two stacks, the ITO/WO3/lithium-polymer electrolyte/ITO stack has a larger absorptance (i.e., approximately 99% at a driving voltage of 3.5 V). The experimental results show that the smart window incorporating an ITO/WO3/lithium-polymer electrolyte/ITO stack with an electrolyte thickness of 1.0 μm provides an indoor illuminance range of 750–1,500 Lux under typical summertime conditions in Taiwan. PMID:22368474

  2. Application of split window technique to TIMS data

    NASA Technical Reports Server (NTRS)

    Matsunaga, Tsuneo; Rokugawa, Shuichi; Ishii, Yoshinori

    1992-01-01

    Absorptions by the atmosphere in thermal infrared region are mainly due to water vapor, carbon dioxide, and ozone. As the content of water vapor in the atmosphere greatly changes according to weather conditions, it is important to know its amount between the sensor and the ground for atmospheric corrections of thermal Infrared Multispectral Scanner (TIMS) data (i.e. radiosonde). On the other hand, various atmospheric correction techniques were already developed for sea surface temperature estimations from satellites. Among such techniques, Split Window technique, now widely used for AVHRR (Advanced Very High Resolution Radiometer), uses no radiosonde or any kind of supplementary data but a difference between observed brightness temperatures in two channels for estimating atmospheric effects. Applications of Split Window technique to TIMS data are discussed because availability of atmospheric profile data is not clear when ASTER operates. After these theoretical discussions, the technique is experimentally applied to TIMS data at three ground targets and results are compared with atmospherically corrected data using LOWTRAN 7 with radiosonde data.

  3. BIPV-powered smart windows utilizing photovoltaic and electrochromic devices.

    PubMed

    Ma, Rong-Hua; Chen, Yu-Chia

    2012-01-01

    A BIPV-powered smart window comprising a building-integrated photovoltaic (BIPV) panel and an all-solid-state electrochromic (EC) stack is proposed. In the proposed device, the output voltage of the BIPV panel varies in accordance with the intensity of the incident light and is modulated in such a way as to generate the EC stack voltage required to maintain the indoor illuminance within a specified range. Two different EC stacks are fabricated and characterized, namely one stack comprising ITO/WO(3)/Ta(2)O(5)/ITO and one stack comprising ITO/WO(3)/lithium-polymer electrolyte/ITO. It is shown that of the two stacks, the ITO/WO(3)/lithium-polymer electrolyte/ITO stack has a larger absorptance (i.e., approximately 99% at a driving voltage of 3.5 V). The experimental results show that the smart window incorporating an ITO/WO(3)/lithium-polymer electrolyte/ITO stack with an electrolyte thickness of 1.0 μm provides an indoor illuminance range of 750-1,500 Lux under typical summertime conditions in Taiwan.

  4. An effective approach for obtaining optimal sampling windows for population pharmacokinetic experiments.

    PubMed

    Ogungbenro, Kayode; Aarons, Leon

    2009-01-01

    This paper describes an effective approach for optimizing sampling windows for population pharmacokinetic experiments. Sampling windows has been proposed for population pharmacokinetic experiments that are conducted in late phase drug development programs where patients are enrolled in many centers and out-patient clinic settings. Collection of samples under this uncontrolled environment at fixed times may be problematic and can result in uninformative data. A sampling windows approach is more practicable, as it provides the opportunity to control when samples are collected by allowing some flexibility and yet provide satisfactory parameter estimation. This approach uses D-optimality to specify time intervals around fixed D-optimal time points that results in a specified level of efficiency. The sampling windows have different lengths and achieve two objectives: the joint sampling windows design attains a high specified efficiency level and also reflects the sensitivities of the plasma concentration-time profile to parameters. It is shown that optimal sampling windows obtained using this approach are very efficient for estimating population PK parameters and provide greater flexibility in terms of when samples are collected.

  5. Window contamination on Expose-R

    NASA Astrophysics Data System (ADS)

    Demets, R.; Bertrand, M.; Bolkhovitinov, A.; Bryson, K.; Colas, C.; Cottin, H.; Dettmann, J.; Ehrenfreund, P.; Elsaesser, A.; Jaramillo, E.; Lebert, M.; van Papendrecht, G.; Pereira, C.; Rohr, T.; Saiagh, K.

    2015-01-01

    Expose is a multi-user instrument for astrobiological and astrochemical experiments in space. Installed at the outer surface of the International Space Station, it enables investigators to study the impact of the open space environment on biological and biochemical test samples. Two Expose missions have been completed so far, designated as Expose-E (Rabbow et al. 2012) and Expose-R (Rabbow et al. this issue). One of the space-unique environmental factors offered by Expose is full-spectrum, ultraviolet (UV)-rich electromagnetic radiation from the Sun. This paper describes and analyses how on Expose-R, access of the test samples to Solar radiation degraded during space exposure in an unpredicted way. Several windows in front of the Sun-exposed test samples acquired a brown shade, resulting in a reduced transparency in visible light, UV and vacuum UV (VUV). Post-flight investigations revealed the discolouration to be caused by a homogenous film of cross-linked organic polymers at the inside of the windows. The chemical signature varied per sample carrier. No such films were found on windows from sealed, pressurized compartments, or on windows that had been kept out of the Sun. This suggests that volatile compounds originating from the interior of the Expose facility were cross-linked and photo-fixed by Solar irradiation at the rear side of the windows. The origin of the volatiles was not fully identified; most probably there was a variety of sources involved including the biological test samples, adhesives, plastics and printed circuit boards. The outer surface of the windows (pointing into space) was chemically impacted as well, with a probable effect on the transparency in VUV. The reported analysis of the window contamination on Expose-R is expected to help the interpretation of the scientific results and offers possibilities to mitigate this problem on future missions - in particular Expose-R2, the direct successor of Expose-R.

  6. X-Windows Socket Widget Class

    NASA Technical Reports Server (NTRS)

    Barry, Matthew R.

    2006-01-01

    The X-Windows Socket Widget Class ("Class" is used here in the object-oriented-programming sense of the word) was devised to simplify the task of implementing network connections for graphical-user-interface (GUI) computer programs. UNIX Transmission Control Protocol/Internet Protocol (TCP/IP) socket programming libraries require many method calls to configure, operate, and destroy sockets. Most X Windows GUI programs use widget sets or toolkits to facilitate management of complex objects. The widget standards facilitate construction of toolkits and application programs. The X-Windows Socket Widget Class encapsulates UNIX TCP/IP socket-management tasks within the framework of an X Windows widget. Using the widget framework, X Windows GUI programs can treat one or more network socket instances in the same manner as that of other graphical widgets, making it easier to program sockets. Wrapping ISP socket programming libraries inside a widget framework enables a programmer to treat a network interface as though it were a GUI.

  7. The rarefaction wave propagation in transparent windows

    NASA Astrophysics Data System (ADS)

    Glam, B.; Porat, E.; Horovitz, Y.; Yosef-Hai, A.

    2017-01-01

    The radial (lateral) rarefaction wave velocity of polymethyl methacrylate (PMMA) and Lithium Fluoride (LiF) windows were studied by plate impact experiments that were carried out at Soreq NRC up to a pressure of 146 kbar in the PMMA and 334 kbar in the LiF. The windows were glued to Lead targets that were impacted by a copper impactor. The VISAR measurement was done in the window interface with the target. This information was utilized to identify the radial rarefaction arrival time at the center of different diameter windows after the shock event, and served as a measurement to the radial wave velocity in the shocked material. It was found that for both windows, LiF or PMMA, the measured radial wave velocity increases with the pressure. Furthermore, this velocity is significantly higher compared to the expected longitudinal sound velocity at the same pressure, calculated by the Steinberg EOS in the PMMA and by ab initio calculation in the LiF. Here we present the experimental results and a comparison with analytical calculation of the sound velocity using the Steinberg EOS.

  8. Measurement and optimization of electrical process window

    NASA Astrophysics Data System (ADS)

    Chan, Tuck-Boon; Kagalwalla, Abde Ali; Gupta, Puneet

    2010-03-01

    Process window (PW) is a collection of values of process parameters that allow circuit to be printed and to operate under desired specifications. Conventional process window which is determined through geometrical fidelity, geometric process window (GPW), does not account for lithography effects on electrical metrics such as delay and power. In contrast to GPW, this paper introduces electrical process window (EPW) which accounts for electrical specifications. Process parameters are considered within EPW if the performance (delay and leakage power) of printed circuit is within desired specifications. Our experiment results show that the area of EPW is 1.5~6x larger than that of GPW. This implies that even if a layout falls outside geometric tolerance, the electrical performance of the circuit may satisfy desired specifications. In addition to process window evaluation, we show that EPW can be enlarged by 10% on average using gate length biasing and Vth push. We also propose approximate methods to evaluate EPW, which can be used in the absence of any design information. Our results show that the proposed approximation method can estimate more than 80% of the area of reference EPW.

  9. Microelectronic device package with an integral window

    DOEpatents

    Peterson, Kenneth A.; Watson, Robert D.

    2002-01-01

    An apparatus for packaging of microelectronic devices, including an integral window. The microelectronic device can be a semiconductor chip, a CCD chip, a CMOS chip, a VCSEL chip, a laser diode, a MEMS device, or a IMEMS device. The package can include a cofired ceramic frame or body. The package can have an internal stepped structure made of one or more plates, with apertures, which are patterned with metallized conductive circuit traces. The microelectronic device can be flip-chip bonded on the plate to these traces, and oriented so that the light-sensitive side is optically accessible through the window. A cover lid can be attached to the opposite side of the package. The result is a compact, low-profile package, having an integral window that can be hermetically-sealed. The package body can be formed by low-temperature cofired ceramic (LTCC) or high-temperature cofired ceramic (HTCC) multilayer processes with the window being simultaneously joined (e.g. cofired) to the package body during LTCC or HTCC processing. Multiple chips can be located within a single package. The cover lid can include a window. The apparatus is particularly suited for packaging of MEMS devices, since the number of handling steps is greatly reduced, thereby reducing the potential for contamination.

  10. Rugged sensor window materials for harsh environments

    NASA Astrophysics Data System (ADS)

    Bayya, Shyam; Villalobos, Guillermo; Kim, Woohong; Sanghera, Jasbinger; Hunt, Michael; Aggarwal, Ishwar D.

    2014-09-01

    There are several military or commercial systems operating in very harsh environments that require rugged windows. On some of these systems, windows become the single point of failure. These applications include sensor or imaging systems, high-energy laser weapons systems, submarine photonic masts, IR countermeasures and missiles. Based on the sea or land or air based platforms the window or dome on these systems must withstand wave slap, underwater or ground based explosions, or survive flight through heavy rain and sand storms while maintaining good optical transmission in the desired wavelength range. Some of these applications still use softer ZnS or fused silica windows because of lack of availability of rugged materials in shapes or sizes required. Sapphire, ALON and spinel are very rugged materials with significantly higher strengths compared to ZnS and fused silica. There have been recent developments in spinel, ALON and sapphire materials to fabricate in large sizes and conformal shapes. We have been developing spinel ceramics for several of these applications. We are also developing β-SiC as a transparent window material as it has higher hardness, strength, and toughness than sapphire, ALON and spinel. This paper gives a summary of our recent findings.

  11. The Moving Window Technique: A Window into Developmental Changes in Attention during Facial Emotion Recognition

    ERIC Educational Resources Information Center

    Birmingham, Elina; Meixner, Tamara; Iarocci, Grace; Kanan, Christopher; Smilek, Daniel; Tanaka, James W.

    2013-01-01

    The strategies children employ to selectively attend to different parts of the face may reflect important developmental changes in facial emotion recognition. Using the Moving Window Technique (MWT), children aged 5-12 years and adults ("N" = 129) explored faces with a mouse-controlled window in an emotion recognition task. An…

  12. Window type: paired 2x4 multipaned steel windows flanked by 1x4 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Window type: paired 2x4 multipaned steel windows flanked by 1x4 multipaned steel casements, breaking building corner. Raised panel door front entry also illustrated. Ground floor detail Building 19, facing north - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  13. Window type: 4x4 multipaned steel window flanked by 1x4 multipaned ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Window type: 4x4 multipaned steel window flanked by 1x4 multipaned steel, casements. Concrete stoop, entry overhang and pipe rail detail also illustrated. Building 36, facing northwest - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  14. Window type: paired 3x2 multipaned steel window flanked by 1x3 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Window type: paired 3x2 multipaned steel window flanked by 1x3 multipaned steel casements, breaking building corner. Broad overhanging eave also illustrated. Second story detail. Building 13, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  15. Why No Windows (Was: A Thin Window for the SubHarmonic Drive Experiment)

    SciTech Connect

    Hill, M.; Walz, D.; /SLAC

    2005-10-12

    We discuss the window requirements for isolating the vacuum chamber for the subharmonic drive experiment from the NLCTA vacuum. We consider mechanical and heat stress, as well as looking at multiple scattering due to the foil. We decide that a window would not be appropriate because of multiple scattering.

  16. 30 CFR 18.30 - Windows and lenses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Windows and lenses. 18.30 Section 18.30 Mineral... § 18.30 Windows and lenses. (a) MSHA may waive testing of materials for windows or lenses except headlight lenses. When tested, material for windows or lenses shall meet the test requirements prescribed...

  17. 49 CFR 238.114 - Rescue access windows.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Rescue access windows. 238.114 Section 238.114... § 238.114 Rescue access windows. (a) Number and location. Except as provided in paragraph (a)(1)(ii) of... rescue access windows. At least one rescue access window shall be located in each side of the...

  18. 30 CFR 18.30 - Windows and lenses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Windows and lenses. 18.30 Section 18.30 Mineral... § 18.30 Windows and lenses. (a) MSHA may waive testing of materials for windows or lenses except headlight lenses. When tested, material for windows or lenses shall meet the test requirements prescribed...

  19. 46 CFR 127.440 - Operability of window coverings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Operability of window coverings. 127.440 Section 127.440... ARRANGEMENTS Construction of Windows, Visibility, and Operability of Coverings § 127.440 Operability of window coverings. Any covering or protection placed over a window or porthole that could be used as a means...

  20. 30 CFR 18.30 - Windows and lenses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Windows and lenses. 18.30 Section 18.30 Mineral... § 18.30 Windows and lenses. (a) MSHA may waive testing of materials for windows or lenses except headlight lenses. When tested, material for windows or lenses shall meet the test requirements prescribed...

  1. 49 CFR 238.114 - Rescue access windows.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Rescue access windows. 238.114 Section 238.114... § 238.114 Rescue access windows. (a) Number and location. Except as provided in paragraph (a)(1)(ii) of... rescue access windows. At least one rescue access window shall be located in each side of the...

  2. 46 CFR 127.440 - Operability of window coverings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Operability of window coverings. 127.440 Section 127.440... ARRANGEMENTS Construction of Windows, Visibility, and Operability of Coverings § 127.440 Operability of window coverings. Any covering or protection placed over a window or porthole that could be used as a means...

  3. 46 CFR 127.440 - Operability of window coverings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Operability of window coverings. 127.440 Section 127.440... ARRANGEMENTS Construction of Windows, Visibility, and Operability of Coverings § 127.440 Operability of window coverings. Any covering or protection placed over a window or porthole that could be used as a means...

  4. 46 CFR 127.440 - Operability of window coverings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Operability of window coverings. 127.440 Section 127.440... ARRANGEMENTS Construction of Windows, Visibility, and Operability of Coverings § 127.440 Operability of window coverings. Any covering or protection placed over a window or porthole that could be used as a means...

  5. 49 CFR 238.113 - Emergency window exits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Emergency window exits. 238.113 Section 238.113... § 238.113 Emergency window exits. (a) Number and location. Except as provided in paragraph (a)(3) of... window exits. At least one emergency window exit shall be located in each side of each end (half) of...

  6. 46 CFR 127.440 - Operability of window coverings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Operability of window coverings. 127.440 Section 127.440... ARRANGEMENTS Construction of Windows, Visibility, and Operability of Coverings § 127.440 Operability of window coverings. Any covering or protection placed over a window or porthole that could be used as a means...

  7. 49 CFR 238.113 - Emergency window exits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Emergency window exits. 238.113 Section 238.113... § 238.113 Emergency window exits. (a) Number and location. Except as provided in paragraph (a)(3) of... window exits. At least one emergency window exit shall be located in each side of each end (half) of...

  8. Optimal blood sampling time windows for parameter estimation using a population approach: design of a phase II clinical trial.

    PubMed

    Chenel, Marylore; Ogungbenro, Kayode; Duval, Vincent; Laveille, Christian; Jochemsen, Roeline; Aarons, Leon

    2005-12-01

    The objective of this paper is to determine optimal blood sampling time windows for the estimation of pharmacokinetic (PK) parameters by a population approach within the clinical constraints. A population PK model was developed to describe a reference phase II PK dataset. Using this model and the parameter estimates, D-optimal sampling times were determined by optimising the determinant of the population Fisher information matrix (PFIM) using PFIM_ _M 1.2 and the modified Fedorov exchange algorithm. Optimal sampling time windows were then determined by allowing the D-optimal windows design to result in a specified level of efficiency when compared to the fixed-times D-optimal design. The best results were obtained when K(a) and IIV on K(a) were fixed. Windows were determined using this approach assuming 90% level of efficiency and uniform sample distribution. Four optimal sampling time windows were determined as follow: at trough between 22 h and new drug administration; between 2 and 4 h after dose for all patients; and for 1/3 of the patients only 2 sampling time windows between 4 and 10 h after dose, equal to [4 h-5 h 05] and [9 h 10-10 h]. This work permitted the determination of an optimal design, with suitable sampling time windows which was then evaluated by simulations. The sampling time windows will be used to define the sampling schedule in a prospective phase II study.

  9. Infrared absorption cross sections of alternative CFCs

    NASA Technical Reports Server (NTRS)

    Clerbaux, Cathy; Colin, Reginald; Simon, Paul C.

    1994-01-01

    Absorption cross sections have obtained in the infrared atmospheric window, between 600 and 1500 cm(exp -1), for 10 alternative hydrohalocarbons: HCFC-22, HCFC-123, HCFC-124, HCFC-141b, HCFC-142b, HCFC-225ca, HCFC-225cb, HFC-125, HFC-134a, and HFC-152a. The measurements were made at three temperatures (287K, 270K and 253K) with a Fourier transform spectrometer operating at 0.03 cm(exp -1) apodized resolution. Integrated cross sections are also derived for use in radiative models to calculate the global warming potentials.

  10. The NH3 spectrum in Saturn's 5 micron window

    NASA Technical Reports Server (NTRS)

    Bjoraker, G. L.; Fink, U.; Larson, H. P.; Johnson, J. R.

    1983-01-01

    Spectra of Saturn's 5-micron window were obtained at the Infrared Telescope Facility on Mauna Kea, Hawaii. The spectra have a resolution of 1.2/cm, and some exhibit extremely low amounts of approximately 300-micron ppt telluric H2O. The Saturn spectra show absorptions by the 2nu2 band of NH3. Long-path laboratory comparison spectra of NH3 were acquired and show considerable deviations in intensity from theoretical predictions. The calibration of Saturn's observed NH3 features with the laboratory data gives 2.0 + or - 0.5 m-amagat of NH3 using the 2nu2 Q-branch at 5.32 microns. The R(1) and R(2) lines yield an abundance about 3 times greater. Absorptions outside the range of the Q-branch can be accounted for by solid NH3 of 10-20 microns equivalent path length. The origin of Saturn's 5-micron flux is mostly thermal with some admixture of solar reflected radiation. A depletion of Saturn's NH3 abundance below the solar value is indicated, but confirmation of this conclusion will require a better understanding of the atmospheric penetration depth at 5 microns and more rigorous modeling of the spectral line formation.

  11. Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation.

    PubMed

    Zou, Jing; Saulnier, Patrick; Perrier, Thomas; Zhang, Ya; Manninen, Tommi; Toppila, Esko; Pyykkö, Ilmari

    2008-10-01

    Hearing loss is a major public health problem, and its treatment with traditional therapy strategies is often unsuccessful due to limited drug access deep in the temporal bone. Multifunctional nanoparticles that are targeted to specified cell populations, biodegradable, traceable in vivo, and equipped with controlled drug/gene release may resolve this problem. We developed lipid core nanocapsules (LNCs) with sizes below 50 nm. The aim of the present study is to evaluate the ability of the LNCs to pass through the round window membrane and reach inner ear targets. FITC was incorporated as a tag for the LNCs and Nile Red was encapsulated inside the oily core to assess the integrity of the LNCs. The capability of LNCs to pass through the round window membrane and the distribution of the LNCs inside the inner ear were evaluated in rats via confocal microscopy in combination with image analysis using ImageJ. After round window membrane administration, LNCs reached the spiral ganglion cells, nerve fibers, and spiral ligament fibrocytes within 30 min. The paracellular pathway was the main approach for LNC penetration of the round window membrane. LNCs can also reach the vestibule, middle ear mucosa, and the adjacent artery. Nuclear localization was detected in the spiral ganglion, though infrequently. These results suggest that LNCs are potential vectors for drug delivery into the spiral ganglion cells, nerve fibers, hair cells, and spiral ligament.

  12. Combined Pressure and Thermal Window System for Space Vehicles

    NASA Technical Reports Server (NTRS)

    Svartstrom, Kirk Nils (Inventor)

    2015-01-01

    A window system for a vehicle comprising a pressure and thermal window pane, a seal system, and a retainer system. The pressure and thermal window pane may be configured to provide desired pressure protection and desired thermal protection when exposed to an environment around the vehicle during operation of the vehicle. The pressure and thermal window pane may have a desired ductility. The seal system may be configured to contact the pressure and thermal window pane to seal the pressure and thermal window pane. The retainer system may be configured to hold the seal system and the pressure and thermal window pane.

  13. Combined Pressure and Thermal Window System for Space Vehicles

    NASA Technical Reports Server (NTRS)

    Svartstrom, Kirk Nils (Inventor)

    2017-01-01

    A window system for a vehicle comprising a pressure and thermal window pane, a seal system, and a retainer system. The pressure and thermal window pane may be configured to provide desired pressure protection and desired thermal protection when exposed to an environment around the vehicle during operation of the vehicle. The pressure and thermal window pane may have a desired ductility. The seal system may be configured to contact the pressure and thermal window pane to seal the pressure and thermal window pane. The retainer system may be configured to hold the seal system and the pressure and thermal window pane.

  14. High-Temperature Optical Window Design

    NASA Technical Reports Server (NTRS)

    Roeloffs, Norman; Taranto, Nick

    1995-01-01

    A high-temperature optical window is essential to the optical diagnostics of high-temperature combustion rigs. Laser Doppler velocimetry, schlieren photography, light sheet visualization, and laser-induced fluorescence spectroscopy are a few of the tests that require optically clear access to the combustor flow stream. A design was developed for a high-temperature window that could withstand the severe environment of the NASA Lewis 3200 F Lean Premixed Prevaporized (LPP) Flame Tube Test Rig. The development of this design was both time consuming and costly. This report documents the design process and the lessons learned, in an effort to reduce the cost of developing future designs for high-temperature optical windows.

  15. A simple hazemeter for window pollution assessment

    NASA Astrophysics Data System (ADS)

    Toy, M.; White, M. R.

    1980-03-01

    Window dirtiness is an obvious result of air pollution. The hazemeter described is a cheap and proven device for assessing two optical factors related to this. The value of measuring direct transmission loss is immediately apparent. The value of the haze or scattered light factor is not so obvious. It affects the total light passed through the window and was shown to have correlations with some of the psychological tests of which a brief mention has been made. The potential of this instrument can be extended to the design of more sophisticated analyses of the effect of pollution on windows; for example, the correlation of optical factors with deposit gauge and rain gauge readings, spectral distributions (say at twilight) and the effect on drivers of dirty windscreens.

  16. Apparatus for insulating windows and the like

    DOEpatents

    Mitchell, R.A.

    1984-06-19

    Apparatus for insulating window openings through walls and the like includes a thermal shutter, a rail for mounting the shutter adjacent to the window opening and a coupling for connecting the shutter to the rail. The thermal shutter includes an insulated panel adhered to frame members which surround the periphery of the panel. The frame members include a hard portion for providing the frame and a soft portion for providing a seal with that portion of the wall adjacent to the periphery of the opening. The coupling means is preferably integral with the attachment rail. According to a preferred embodiment, the coupling means includes a continuous hinge of reduced thickness. The thermal shutter can be permanently attached, hinged, bi-folded, or sliding with respect to the window and wall. A distribution method is to market the apparatus in kit'' form. 11 figs.

  17. Apparatus for insulating windows and the like

    DOEpatents

    Mitchell, Robert A.

    1984-01-01

    Apparatus for insulating window openings through walls and the like includes a thermal shutter, a rail for mounting the shutter adjacent to the window opening and a coupling for connecting the shutter to the rail. The thermal shutter includes an insulated panel adhered to frame members which surround the periphery of the panel. The frame members include a hard portion for providing the frame and a soft portion for providing a seal with that portion of the wall adjacent to the periphery of the opening. The coupling means is preferably integral with the attachment rail. According to a preferred embodiment, the coupling means includes a continuous hinge of reduced thickness. The thermal shutter can be permanently attached, hinged, bi-folded, or sliding with respect to the window and wall. A distribution method is to market the apparatus in "kit" form.

  18. Single-agent parallel window search

    NASA Technical Reports Server (NTRS)

    Powley, Curt; Korf, Richard E.

    1991-01-01

    Parallel window search is applied to single-agent problems by having different processes simultaneously perform iterations of Iterative-Deepening-A(asterisk) (IDA-asterisk) on the same problem but with different cost thresholds. This approach is limited by the time to perform the goal iteration. To overcome this disadvantage, the authors consider node ordering. They discuss how global node ordering by minimum h among nodes with equal f = g + h values can reduce the time complexity of serial IDA-asterisk by reducing the time to perform the iterations prior to the goal iteration. Finally, the two ideas of parallel window search and node ordering are combined to eliminate the weaknesses of each approach while retaining the strengths. The resulting approach, called simply parallel window search, can be used to find a near-optimal solution quickly, improve the solution until it is optimal, and then finally guarantee optimality, depending on the amount of time available.

  19. Radcalc for Windows. Volume 2: Technical manual

    SciTech Connect

    Green, J.R.

    1995-09-27

    Radcalc for Windows is a user-friendly menu-driven Windows-compatible software program with applications in the transportation of radioactive materials. It calculates the radiolytic generation of hydrogen gas in the matrix of low-level and high-level radioactive waste using NRC-accepted methodology. It computes the quantity of a radionuclide and its associated products for a given period of time. In addition, the code categorizes shipment quantities as radioactive, Type A or Type B, limited quantity, low specific activity, highway route controlled, and fissile excepted using DOT definitions and methodologies, as outlined in 49 CFR Subchapter C. The code has undergone extensive testing and validation. Volume I is a User`s Guide, and Volume II is the Technical Manual for Radcalc for Windows

  20. Integral window hermetic fiber optic components

    SciTech Connect

    Dalton, R.D.; Kramer, D.P.; Massey, R.T.; Waker, D.A.

    1994-12-31

    In the fabrication of igniters, actuators, detonators, and other pyrotechnic devices to be activated by a laser beam, an integral optical glass window is formed by placing a preform in the structural member of the device and then melting the glass and sealing it in place by heating at a temperature between the ceramming temperature of the glass and the melting point of the metal, followed by rapid furnace cooling to avoid devitrification. No other sealing material is needed to achieve hermeticity. A preferred embodiment of this type of device is fabricated by allowing the molten glass to flow further and form a plano-convex lens integral with and at the bottom of the window. The lens functions to decrease the beam divergence caused by refraction of the laser light passing through the window when the device is fired by means of a laser beam.

  1. Fused silica windows for solar receiver applications

    NASA Astrophysics Data System (ADS)

    Hertel, Johannes; Uhlig, Ralf; Söhn, Matthias; Schenk, Christian; Helsch, Gundula; Bornhöft, Hansjörg

    2016-05-01

    A comprehensive study of optical and mechanical properties of quartz glass (fused silica) with regard to application in high temperature solar receivers is presented. The dependence of rupture strength on different surface conditions as well as high temperature is analyzed, focussing particularly on damage by devitrification and sandblasting. The influence of typical types of contamination in combination with thermal cycling on the optical properties of fused silica is determined. Cleaning methods are compared regarding effectiveness on contamination-induced degradation for samples with and without antireflective coating. The FEM-aided design of different types of receiver windows and their support structure is presented. A large-scale production process has been developed for producing fused silica dome shaped windows (pressurized window) up to a diameter of 816 mm. Prototypes were successfully pressure-tested in a test bench and certified according to the European Pressure Vessel Directive.

  2. Integration Window Position Estimation in TR Receivers

    SciTech Connect

    Nekoogar, F; Dowla, F; Spiridon, A

    2005-03-15

    Transmitted-reference (TR) receivers avoid the stringent synchronization requirements that exist in conventional pulse detection schemes. However, the performance of such receivers is highly sensitive to precise timing acquisition and tracking as well as the length of their integration window. This window in TR receivers defines the limits of the finite integrator prior to the final decision making block. In this paper, we propose a novel technique that allows us to extract the timing information of the integration window very accurately in UWB-TR receivers in the presence of channel noise. The principles of the method are presented and the BER performance of a modified UWB-TR receiver is investigated by computer simulation. Our studies show that the proposed estimation technique adds value to the conventional TR receiver structure with modest increase in complexity.

  3. The Intestinal Absorption of Folates

    PubMed Central

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I. David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

  4. Error-Based Design Space Windowing

    NASA Technical Reports Server (NTRS)

    Papila, Melih; Papila, Nilay U.; Shyy, Wei; Haftka, Raphael T.; Fitz-Coy, Norman

    2002-01-01

    Windowing of design space is considered in order to reduce the bias errors due to low-order polynomial response surfaces (RS). Standard design space windowing (DSW) uses a region of interest by setting a requirement on response level and checks it by a global RS predictions over the design space. This approach, however, is vulnerable since RS modeling errors may lead to the wrong region to zoom on. The approach is modified by introducing an eigenvalue error measure based on point-to-point mean squared error criterion. Two examples are presented to demonstrate the benefit of the error-based DSW.

  5. Window for radiation detectors and the like

    DOEpatents

    Sparks, C.J. Jr.; Ogle, J.C.

    1975-10-28

    An improved x- and gamma-radiation and particle transparent window for the environment-controlling enclosure of various types of radiation and particle detectors is provided by a special graphite foil of a thickness of from about 0.1 to 1 mil. The graphite must have very parallel hexagonal planes with a mosaic spread no greater than 5$sup 0$ to have the necessary strength in thin sections to support one atmosphere or more of pressure. Such graphite is formed by hot- pressing and annealing pyrolytically deposited graphite and thereafter stripping off layers of sufficient thickness to form the window.

  6. Interior and Exterior Low-E Storm Window Installation

    ScienceCinema

    Witters, Sarah

    2016-07-12

    Until recently, energy-efficient window retrofit options have largely been limited to repair or replacement; leaving the homeowner to decide between affordability and deeper energy savings. A new and improved low-e storm window boasts a combination of curb appeal and energy efficiency, all for a fraction of the cost of window replacement. A recent whole-home experiment performed by PNNL suggests that attaching low-e storm windows can result in as much energy savings replacing the windows.

  7. Interior and Exterior Low-E Storm Window Installation

    SciTech Connect

    Witters, Sarah

    2014-09-03

    Until recently, energy-efficient window retrofit options have largely been limited to repair or replacement; leaving the homeowner to decide between affordability and deeper energy savings. A new and improved low-e storm window boasts a combination of curb appeal and energy efficiency, all for a fraction of the cost of window replacement. A recent whole-home experiment performed by PNNL suggests that attaching low-e storm windows can result in as much energy savings replacing the windows.

  8. Ingestion of drugs by "parachuting": a unique drug delivery technique.

    PubMed

    Kenerson, Katherine L; Lear-Kaul, Kelly C

    2012-06-01

    "Parachuting" is a technique of drug delivery where medications or illicit drugs are ingested by wrapping the drug of choice in a covering, which then will dissolve or unravel in the gastrointestinal tract, thereby releasing the drug for absorption. Parachuting of drugs can entail crushing of a pill prior to packaging to theoretically increase the surface area for absorption or may involve the packaging of a higher than usual dose of a drug in attempts to attain a sustained-release effect as the "parachute" dissolves or unravels. A case is presented in which a prescription drug abuser known to parachute his medications dies from obstruction of his airway by the inhaled packet. Risks of parachuting any drug would include overdose and fatal toxic effect from the drug itself and adverse effects from the packaging including bowel obstruction or perforation, or airway obstruction.

  9. Aberration and boresight error correction for conformal aircraft windows using the inner window surface and tilted fixed correctors.

    PubMed

    Zhao, Chunzhu; Cui, Qingfeng; Mao, Shan

    2016-04-01

    A static solution to aberrations and boresight error for tilted conformal aircraft windows at different look angles is reported. The solution uses the inner window surface to correct the window aberrations at a 0° look angle and uses fixed correctors behind the window to correct the residual window aberrations at other look angles. Then, the boresight error for the window at different look angles is corrected by tilting the fixed correctors. The principle of the solution is discussed, and a design example shows that the solution is effective in correcting the aberrations and boresight error for a tilted conformal aircraft window at different look angles.

  10. Nearedge Absorption Spectroscopy of Interplanetary Dust Particles

    SciTech Connect

    Brennan, S.; Luening, K.; Pianetta, P.; Bradley, J.; Graham, G.; Westphal, A.; Snead, C.; Dominguez, G.; /SLAC, SSRL

    2006-10-25

    Interplanetary Dust Particles (IDPs) are derived from primitive Solar System bodies like asteroids and comets. Studies of IDPs provide a window onto the origins of the solar system and presolar interstellar environments. We are using Total Reflection X-ray Fluorescence (TXRF) techniques developed for the measurement of the cleanliness of silicon wafer surfaces to analyze these particles with high detection sensitivity. In addition to elemental analysis of the particles, we have collected X-ray Absorption Near-Edge spectra in a grazing incidence geometry at the Fe and Ni absorption edges for particles placed on a silicon wafer substrate. We find that the iron is dominated by Fe{sub 2}O{sub 3}.

  11. Atmospheric absorption cell characterization

    NASA Astrophysics Data System (ADS)

    1982-06-01

    The measurement capability of the Avionics Laboratory IR Facility was used to evaluate an absorption cell that will be used to simulate atmospheric absorption over horizontal paths of 1 - 10 km in length. Band models were used to characterize the transmittance of carbon dioxide (CO2), nitrogen (N2), and nitrous oxide (N2O) in the cell. The measured transmittance was compared to the calculated values. Nitrous oxide is important in the 4 - 4.5 micron range in shaping the weak line absorption of carbon dioxide. The absorption cell is adequate for simulating atmospheric absorption over these paths.

  12. Considerations When Upgrading and Renovating Window Systems

    ERIC Educational Resources Information Center

    Gille, Steve

    2010-01-01

    Today's educational facilities managers face many challenges. As stewards of their campus' physical assets, these professionals are charged with improving students' learning environments, saving money, and maintaining the historical and aesthetic integrity of their buildings. For schools and universities that have not replaced their windows in…

  13. Creation Stories: Windows to Cultural Values.

    ERIC Educational Resources Information Center

    Hodges, David H.

    1995-01-01

    Maintains that a difficulty in teaching humanities survey courses is coordinating data from the various disciplines of cultural history. Recommends the use of creation stories as "windows" on the cultures of the Egyptians, Mesopotamians, and the Hebrews. Provides an overview of each culture's creation stories and a bibliography of…

  14. Schools Facing the Expiration of Windows XP

    ERIC Educational Resources Information Center

    Cavanagh, Sean

    2013-01-01

    Microsoft's plans to end support for Windows XP, believed to be the dominant computer operating system in K-12 education, could pose big technological and financial challenges for districts nationwide--issues that many school systems have yet to confront. The giant software company has made it clear for years that it plans to stop supporting XP…

  15. Windows 8: What Educators Need to Know

    ERIC Educational Resources Information Center

    Vedder, Richard G.

    2012-01-01

    In October 2012, Microsoft will release the commercial version of its next operating system, presently called "Windows 8." This version represents a significant departure from the past. Microsoft wants this operating system to meet user needs regardless of physical platform (e.g., desktop, notebook, tablet, mobile phone). As part of this mission,…

  16. Dressed fluxon in a Josephson window junction

    NASA Astrophysics Data System (ADS)

    Caputo, Jean Guy; Flytzanis, Nikos; Devoret, Michel

    1994-09-01

    The static fluxon solutions of a Josephson window junction have been studied numerically. We show that the effect of the idle region surrounding the junction is to ``dress'' the fluxon causing its energy to increase. This effect can be predicted accurately by a simple model.

  17. Ada To X-Window Bindings

    NASA Technical Reports Server (NTRS)

    Souleles, Dean

    1993-01-01

    Ada to X-Window Bindings computer program developed to provide Ada programmers with complete interfaces to Xt Intrinsics and OSF Motif toolkits. Provides "Ada view" of some mostly C-language programming libraries. Package of software written in Ada and C languages.

  18. A simple image display application for windows.

    PubMed

    Conrad, G R

    1997-08-01

    The purpose of this project was to develop a simple application for displaying low-to-moderate resolution digital images under the Windows operating environment. The display of scintigraphic images was of special interest, and for this reason the program was designed to show sequences of images and to account for broad ranges of pixel values. In order to function under a variety of Windows versions, the program was developed using the 16-bit Microsoft C +2 compiler and targeted for Windows 3.1 enhanced. It was tested with Trionix images for nuclear medicine and Siemens for computed tomography (CT) and magnetic resonance (MR). The resulting application, called SID, successfully read Magnetom, Somatom, Trionix, and Interfile images of dimension 512 or less on Intel-based Windows PCs with 256 color SVGA-compatible (Super Video Graphics Adapters) video hardware. Early applications of the program included remote monitoring of image studies, resident review of teaching cases, review of research images, and preparation of educational materials. This article describes the features, operation, and potential applications of SID.

  19. Learning in Lectures: Do 'Interactive Windows' Help?

    ERIC Educational Resources Information Center

    Huxham, Mark

    2005-01-01

    Many educational development resources recommend making conventional lectures more interactive. However, there is little firm evidence supporting either the acceptability (to students) or efficacy of doing so. This research examined the use of short 'interactive windows' (discussions and problem-solving exercises) in first year evolution lectures…

  20. Inexpensive anti-fog coating for windows

    NASA Technical Reports Server (NTRS)

    Carmin, D. L., Jr.; Morrison, H. D.

    1971-01-01

    Coating applications include anti-fog protection for deep-sea diving equipment, fire protection helmets, and windows of vehicles used in hazardous environments. Basic coating composition includes liquid detergent, deionized water, and oxygen compatible fire-resistant oil. Composition prevents visor fogging under maximum metabolic load for 5 hours and longer.

  1. New Window into the Human Body

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Michael Vannier, MD, a former NASA engineer, recognized the similarity between NASA's computerized image processing technology and nuclear magnetic resonance. With technical assistance from Kennedy Space Center, he developed a computer program for Mallinckrodt Institute of Radiology enabling Nuclear Magnetic Resonance (NMR) to scan body tissue for earlier diagnoses. Dr. Vannier feels that "satellite imaging" has opened a new window into the human body.

  2. BMDP/Diamond for Windows [software review].

    ERIC Educational Resources Information Center

    Lay, Colette M.

    1996-01-01

    BMDP/Diamond for Windows was developed as a stand-alone software package for initial data exploration and screening. The program uses advanced visualization techniques to allow one to examine the data from different perspectives, or to manipulate graphics to gain greater insight. Data can be checked quickly for a variety of characteristics. (SLD)

  3. Window Presentation Styles and User's Spatial Ability.

    ERIC Educational Resources Information Center

    Bastecki, Victoria L.; Berry, Louis H.

    The purpose of this study was to examine the effects of spatial ability level and window presentation style of tiled and overlapped computer displays on the achievement of dental hygiene students. Participants were 43 first-term Dental Hygiene students enrolled full-time at a University School of Dental Medicine. Phase one of this project…

  4. Engineering adenylate cyclases regulated by near-infrared window light.

    PubMed

    Ryu, Min-Hyung; Kang, In-Hye; Nelson, Mathew D; Jensen, Tricia M; Lyuksyutova, Anna I; Siltberg-Liberles, Jessica; Raizen, David M; Gomelsky, Mark

    2014-07-15

    Bacteriophytochromes sense light in the near-infrared window, the spectral region where absorption by mammalian tissues is minimal, and their chromophore, biliverdin IXα, is naturally present in animal cells. These properties make bacteriophytochromes particularly attractive for optogenetic applications. However, the lack of understanding of how light-induced conformational changes control output activities has hindered engineering of bacteriophytochrome-based optogenetic tools. Many bacteriophytochromes function as homodimeric enzymes, in which light-induced conformational changes are transferred via α-helical linkers to the rigid output domains. We hypothesized that heterologous output domains requiring homodimerization can be fused to the photosensory modules of bacteriophytochromes to generate light-activated fusions. Here, we tested this hypothesis by engineering adenylate cyclases regulated by light in the near-infrared spectral window using the photosensory module of the Rhodobacter sphaeroides bacteriophytochrome BphG1 and the adenylate cyclase domain from Nostoc sp. CyaB1. We engineered several light-activated fusion proteins that differed from each other by approximately one or two α-helical turns, suggesting that positioning of the output domains in the same phase of the helix is important for light-dependent activity. Extensive mutagenesis of one of these fusions resulted in an adenylate cyclase with a sixfold photodynamic range. Additional mutagenesis produced an enzyme with a more stable photoactivated state. When expressed in cholinergic neurons in Caenorhabditis elegans, the engineered adenylate cyclase affected worm behavior in a light-dependent manner. The insights derived from this study can be applied to the engineering of other homodimeric bacteriophytochromes, which will further expand the optogenetic toolset.

  5. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine.

  6. Time-dependent oral absorption models

    NASA Technical Reports Server (NTRS)

    Higaki, K.; Yamashita, S.; Amidon, G. L.

    2001-01-01

    The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

  7. Potassium emission absorption system. Topical report 12

    SciTech Connect

    Bauman, L.E.

    1995-04-01

    The Potassium Emission Absorption System is one of the advanced optical diagnostics developed at Mississippi State University to provide support for the demonstration of prototype-scale coal-fired combustion magnetohydrodynamic (MHD) electrical power generation. Intended for application in the upstream of an MHD flow, the system directly measures gas temperature and neutral potassium atom number density through spectroscopic emission absorption techniques. From these measurements the electron density can be inferred from a statistical equilibrium calculation and the electron conductivity in the MHD channel found by use of an electron mobility model. The instrument has been utilized for field test measurements on MHD facilities for almost a decade and has been proven to provide useful measurements as designed for MHD nozzle, channel, and diffuser test sections. The theory of the measurements, a system description, its capabilities, and field test measurement results are reported here. During the development and application of the instrument several technical issues arose which when addressed advanced the state of the art in emission absorption measurement. Studies of these issues are also reported here and include: two-wavelength measurements for particle-laden flows, potassium D-line far wing absorption coefficient, bias in emission absorption measurements arising from dirty windows and misalignments, non-coincident multiwavelength emission absorption sampling errors, and lineshape fitting for boundary layer flow profile information. Although developed for NLHD application, the instrument could be applied to any high temperature flow with a resonance line in the 300 to 800 nm range, for instance other types of flames, rocket plumes or low temperature plasmas.

  8. Low Loss Window Materials for Chemical Lasers

    DTIC Science & Technology

    1975-08-01

    ß’s extracted are listed in Table 1 along with the earlier ZnSe results which are summarized for completeness. The surface absorption shown is for...15 I I It is untortunate that a meaningful surface absorption could not be extracted from all of this data. It is still felt that SrF^ has...M^^m^ BMaa •^^^w»^1’ ^," •■’ I I I Table 3 Absorption Coefficients for Ge and Si at DF and HF Wavelengths Sample Wavelength (microns) B total

  9. Novel high-pressure windows made of glass-like carbon for x-ray analysis.

    PubMed

    Testemale, Denis; Prat, Alain; Lahera, Eric; Hazemann, Jean-Louis

    2016-07-01

    Original high-pressure glass-like carbon windows developed for x-ray spectroscopy applications are presented. The scientific and technological background of this new technical development is exposed, in particular the limitations of our existing beryllium windows in the context of x-ray absorption spectroscopy (XAS) measurements of solutions with very low solute concentrations at hydrothermal conditions (0.1-200 MPa, 30-600 °C). The benefits of glass-like carbon are exposed, notably its non-crystalline character, the absence of impurities which has been verified by micro-fluorescence laboratory measurements, and its non-toxicity which makes its machining safer. Finite elements mechanical calculations and experimental pressure tests were conducted to determine the pressure limits of windows with two different geometries: cylindrical (thickness 0.5 mm) and inversed-dome shape (thickness 0.5 mm at the tip of the dome). The former break at 150 MPa and the latter show no sign of rupture at 400 MPa. Recent XAS measurements conducted with the new dome shaped windows are presented to show the advantages of the design that allow for the detection of very low concentrations in the transmission mode (down to 30 ppm) and the acquisition of fluorescence XAS spectra in diluted solutions at high pressure. Eventually the perspectives of this original development are discussed.

  10. Novel high-pressure windows made of glass-like carbon for x-ray analysis

    NASA Astrophysics Data System (ADS)

    Testemale, Denis; Prat, Alain; Lahera, Eric; Hazemann, Jean-Louis

    2016-07-01

    Original high-pressure glass-like carbon windows developed for x-ray spectroscopy applications are presented. The scientific and technological background of this new technical development is exposed, in particular the limitations of our existing beryllium windows in the context of x-ray absorption spectroscopy (XAS) measurements of solutions with very low solute concentrations at hydrothermal conditions (0.1-200 MPa, 30-600 °C). The benefits of glass-like carbon are exposed, notably its non-crystalline character, the absence of impurities which has been verified by micro-fluorescence laboratory measurements, and its non-toxicity which makes its machining safer. Finite elements mechanical calculations and experimental pressure tests were conducted to determine the pressure limits of windows with two different geometries: cylindrical (thickness 0.5 mm) and inversed-dome shape (thickness 0.5 mm at the tip of the dome). The former break at 150 MPa and the latter show no sign of rupture at 400 MPa. Recent XAS measurements conducted with the new dome shaped windows are presented to show the advantages of the design that allow for the detection of very low concentrations in the transmission mode (down to 30 ppm) and the acquisition of fluorescence XAS spectra in diluted solutions at high pressure. Eventually the perspectives of this original development are discussed.

  11. WINDOW 4.0: Documentation of calculation procedures

    SciTech Connect

    Finlayson, E.U.; Arasteh, D.K.; Huizenga, C.; Rubin, M.D.; Reilly, M.S.

    1993-07-01

    WINDOW 4.0 is a publicly available IBM PC compatible computer program developed by the Building Technologies Group at the Lawrence Berkeley Laboratory for calculating the thermal and optical properties necessary for heat transfer analyses of fenestration products. This report explains the calculation methods used in WINDOW 4.0 and is meant as a tool for those interested in understanding the procedures contained in WINDOW 4.0. All the calculations are discussed in the International System of units (SI). WINDOW 4.0 is the latest in a series of programs released by the Lawrence Berkeley Laboratory. The WINDOW program has its roots in a paper detailing a method for calculating heat transfer through windows [Rubin, 1982]. WINDOW 4.0 replaces the widely used 3.1 version. Although WINDOW 4.0 is a major revision, many of the algorithms used in WINDOW 4.0 build upon those previously documented [Arasteh, 1989b], [Furler, 1991]. This report documents the calculations that are unchanged from WINDOW 3.1, as well as those calculations that are new to WINDOW 4.0. This report uses the organization of the WINDOW 4.0 program. Results displayed on a WINDOW 4.0 screen are discussed in a section describing that screen. In the conclusion the aspects of the calculation method currently slated for revision are discussed. A glossary of variables used throughout the report is found in Section 11.

  12. Virtual window telepresence system for telerobotic inspection

    NASA Astrophysics Data System (ADS)

    Tharp, Gregory K.; Hayati, Samad; Phan, Linh

    1995-12-01

    Telerobotic inspection can be used in environments that are too hazardous, removed, or expensive for direct human inspection. Telerobotic inspection is a complex task requiring an operator to control and coordinate a robot and sensors, while monitoring and interpreting sensor data to detect flaws. A virtual window telepresence system has been developed to aid the operator in performing these inspections. While the operator is looking at a monitor displaying stereo video from cameras mounted on the robot, the system tracks operator head position and moves the robot to create the illusion that the operator is looking out a window. This interface allows the operator to naturally specify desired viewpoint and enables him to concentrate on the visual examination of the area that may contain a flaw.

  13. Advances in glazing materials for windows

    SciTech Connect

    Not Available

    1994-11-01

    No one type of glazing is suitable for every application. Many materials are available that serve different purposes. Moreover, consumers may discover that they need two types of glazing for a home because of the directions that the windows face and the local climate. To make wise purchases, consumers should first examine their heating and cooling needs and prioritize desired features such as daylighting, solar heating, shading, ventilation, and aesthetic value. Research and development into types of glazing have created a new generation of materials that offer improved window efficiency and performance for consumers. While this new generation of glazing materials quickly gains acceptance in the marketplace, the research and development of even more efficient technology continues.

  14. Colored light application in retail display window

    NASA Astrophysics Data System (ADS)

    Simeonova, Milena; Narendran, Nadarajah

    2002-06-01

    A laboratory experiment was conducted to investigate the usefulness of colored LEDs in retail display window applications. Human subjects viewed two side-by-side, identical mock-up display windows, and rated their preference. Subjects showed strong preference for the colored background, compared to the white background. In general, subjects disliked the modulated intensity background. Furthermore, the use of colored light (static red and blue) on the background allowed the accent light to be decreased without sacrificing visual appeal, ability to capture attention, and ability to see displayed objects clearly. It appears from this initial laboratory study that the amount of accent light can be reduced significantly, which could provide energy savings. We believe a field study would be greatly beneficial for further confirming these results and for quantifying the total energy savings in an actual store.

  15. Diamondlike carbon protective coatings for optical windows

    NASA Technical Reports Server (NTRS)

    Swec, Diane M.; Mirtich, Michael J.

    1989-01-01

    Diamondlike carbon (DLC) films were deposited on infrared transmitting optical windows and were evaluated as protective coatings for these windows exposed to particle and rain erosion. The DLC films were deposited on zinc selenide (ZnSe) and zinc sulfide (ZnS) by three different ion beam methods: (1) sputter deposition from a carbon target using an 8-cm argon ion source; (2) direct deposition by a 30-cm hollow cathode ion source with hydrocarbon gas in argon; and (3) dual beam direct deposition by the 30-cm hollow cathode ion source and an 8-cm argon ion source. In an attempt to improve the adherence of the DLC films on ZnSc and ZnS, ion beam cleaning, ion implantation with helium and neon ions, or sputter deposition of a thin, ion beam intermediate coating was employed prior to deposition of the DLC film. The protection that the DLC films afforded the windows from particle and rain erosion was evaluated, along with the hydrogen content, adherence, intrinsic stress, and infrared transmittance of the films. Because of the elevated stress levels in the ion beam sputtered DLC films and in those ion beam deposited with butane, films thicker than 0.1 micron and with good adherence on ZnS and ZnSe could not be generated. An intermediate coating of germanium successfully allowed the DLC films to remain adherent to the optical windows and caused only negligible reduction in the specular transmittance of the ZnS and ZnSe at 10 microns.

  16. Performance Evaluation of Vinyl Replacement Windows.

    DTIC Science & Technology

    1980-07-15

    VINYL REPLACEMENT WINDOWS P. B. SHEPHERD JOHNS - MANVILLE SALES CORPORATION LEU ! RESEARCH & DEVELOPMENT CENTER CLE 0 KEN-CARYL RANCH DENVER, COLORADO...PE F -I.. E RI.. Philip B.heperd/K^678D00 9. PERFORMING ORGANIZATION NAME AND ADDRESS SO. PROGRAM ELEMENT. PROJECT, TASK Johns - Manville Sales Corporatp...Development Center Ken-Caryl Ranch Denver. Colorado 80217 (303) 979-1000 October 23, 1979 Dear Sir: The Johns - Manville R&D Center has been contacted

  17. Thin-ice Arctic Acoustic Window (THAAW)

    DTIC Science & Technology

    2014-09-30

    STATEMENT A. Approved for public release; distribution is unlimited. Thin- ice Arctic Acoustic Window (THAAW) Peter F. Worcester Scripps Institution of...of the ice cover and extensive warming of the intermediate layers. The multiyear ice is melting . Ice keels are getting smaller. With more open water...determine the fundamental limits to signal processing in the Arctic imposed by ocean and ice processes. The hope is that these first few new steps will

  18. Laser Window Materials and Optical Coating Science

    DTIC Science & Technology

    1977-08-01

    10 Torr pressure , is presently the favored alternative RAP agent. Comparison studies of optical coatings prepared under conventional high...In principle , the uncoated surface heat also contributes to the first and second slopes but in practice, as discussed in the results in Sec. Ill...jim), CO (5.3 jim), and CO2 (9.27 and 10.6 fi.m). The window materials that are under investigation include selected alkali halides and

  19. Improving Wang-Landau sampling with adaptive windows.

    PubMed

    Cunha-Netto, A G; Caparica, A A; Tsai, Shan-Ho; Dickman, Ronald; Landau, D P

    2008-11-01

    Wang-Landau sampling (WLS) of large systems requires dividing the energy range into "windows" and joining the results of simulations in each window. The resulting density of states (and associated thermodynamic functions) is shown to suffer from boundary effects in simulations of lattice polymers and the five-state Potts model. Here, we implement WLS using adaptive windows. Instead of defining fixed energy windows (or windows in the energy-magnetization plane for the Potts model), the boundary positions depend on the set of energy values on which the histogram is flat at a given stage of the simulation. Shifting the windows each time the modification factor f is reduced, we eliminate border effects that arise in simulations using fixed windows. Adaptive windows extend significantly the range of system sizes that may be studied reliably using WLS.

  20. 35. DETAIL VIEW, WEST WINDOW IN WEST ELEVATION GABLE (NOTE: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. DETAIL VIEW, WEST WINDOW IN WEST ELEVATION GABLE (NOTE: THE MOLDED STRINGCOURSE THAT PROJECTS FROM THE BASE OF THE FIRST FLOOR WINDOW ARCH AND VISIBLE WATERTABLE) - Kenworthy Hall, State Highway 14 (Greensboro Road), Marion, Perry County, AL

  1. Evaluation criteria and test methods for electrochromic windows

    SciTech Connect

    Czanderna, A.W. ); Lampert, C.M. )

    1990-07-01

    Report summarizes the test methods used for evaluating electrochromic (EC) windows, and summarizes what is known about degradation of their performance, and recommends methods and procedures for advancing EC windows for buildings applications. 77 refs., 13 figs., 6 tabs.

  2. 44. Interior detail, stone sill, east study window. This is ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. Interior detail, stone sill, east study window. This is the only stone window sill in the house. - John Bartram House & Garden, House, 54th Street & Lindbergh Boulevard, Philadelphia, Philadelphia County, PA

  3. DETAIL, EAST ELEVATION. THIS LUNETTE WINDOW POSITIONED IN A BLIND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL, EAST ELEVATION. THIS LUNETTE WINDOW POSITIONED IN A BLIND ARCH ECHOES A SIMILAR TREATMENT OF THE VENETIAN WINDOWS IN THE HOUSE - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  4. 6. INTERIOR DETAIL OF WINDOW IN EAST WALL NORTH END ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. INTERIOR DETAIL OF WINDOW IN EAST WALL NORTH END ROOM. BUILDING 4 IS VISIBLE THROUGH WINDOW. - Chollas Heights Naval Radio Transmitting Facility, Recreation Building, 6410 Zero Road, San Diego, San Diego County, CA

  5. 16. INTERIOR VIEW OF WINDOWS ABOVE MAIN ENTRANCE ON WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. INTERIOR VIEW OF WINDOWS ABOVE MAIN ENTRANCE ON WEST ELEVATION. THE WINDOWS ARE HINGED AT THE BOTTOM AND OPEN INWARD - Kodiak Naval Operating Base, Gymnasium, U.S. Coast Guard Station, Kodiak, Kodiak Island Borough, AK

  6. 9. Detail of a typical window and a ventilator just ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Detail of a typical window and a ventilator just below the window sill - the only instance of such placement of this feature in the structure. - Perry Township School No. 3, Middle Mount Vernon & Eickhoff Roads, Evansville, Vanderburgh County, IN

  7. 17. LARGE WINDOWS ON NORTH WALL. THE PROTECTIVE WIRE ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. LARGE WINDOWS ON NORTH WALL. THE PROTECTIVE WIRE ON THE INTERIOR CAN BE SEEN. THE WINDOWS HAVE BEEN BOARDED OVER THE EXTERIOR - Kodiak Naval Operating Base, Gymnasium, U.S. Coast Guard Station, Kodiak, Kodiak Island Borough, AK

  8. DETAIL VIEW, OXEYE WINDOW, SOUTH WALL OF SOUTH GARRET. THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW, OX-EYE WINDOW, SOUTH WALL OF SOUTH GARRET. THE MUNTIN PATTERN USED IN THIS WINDOW WAS REFERRED TO AS “GOTHIC” IN THE EIGHTEENTH CENTURY - The Woodlands, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  9. WINDOW WITH ORIGINAL PANELED FOLDING SHUTTERS, SECOND FLOOR FRONT ROOM, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WINDOW WITH ORIGINAL PANELED FOLDING SHUTTERS, SECOND FLOOR FRONT ROOM, LOOKING OUT WALNUT STREET (SOUTH). NOTE ALTERED LOWER SECTION MADE CA. 1840. Compare window in PA-1436 A-37 - Kid-Chandler House, 323 Walnut Street, Philadelphia, Philadelphia County, PA

  10. 13. INTERIOR OF NORTHEAST PHOTO TOWER WITH WINDOW OPEN; ELECTRICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. INTERIOR OF NORTHEAST PHOTO TOWER WITH WINDOW OPEN; ELECTRICAL POWER BOX BELOW WINDOW - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  11. Orthogonal sets of data windows constructed from trigonometric polynomials

    NASA Technical Reports Server (NTRS)

    Greenhall, C. A.

    1989-01-01

    Suboptimal, easily computable substitutes for the discrete prolate-spheroidal windows used by Thomson for spectral estimation are given. Trigonometric coefficients and energy leakages of the window polynomials are tabulated.

  12. 10. TYPICAL SIDE WALL WINDOW AND WATER TABLE. The water ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. TYPICAL SIDE WALL WINDOW AND WATER TABLE. The water table is an extension of the order base, and the lower torus breaks for ventilation, which applies to all windows. - Westminster Presbyterian Church, 273 Meeting Street, Charleston, Charleston County, SC

  13. Crewmembers photographing the Earth from the aft flight deck windows.

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Mission Pilot Mike Baker and Mission Specialist Tamara Jernigan looking out the aft flight deck overhead windows and photographing the Earth below. Jernigan is looking out the window while Baker is photographing with a Hasselblad 70mm camera.

  14. Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs - a case study with valsartan.

    PubMed

    Chella, Naveen; Tadikonda, Ramarao

    2015-06-01

    Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30 min against the plain drug which showed only 11.31% of drug release in 30 min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher Cmax compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.

  15. Rumor Detection over Varying Time Windows.

    PubMed

    Kwon, Sejeong; Cha, Meeyoung; Jung, Kyomin

    2017-01-01

    This study determines the major difference between rumors and non-rumors and explores rumor classification performance levels over varying time windows-from the first three days to nearly two months. A comprehensive set of user, structural, linguistic, and temporal features was examined and their relative strength was compared from near-complete date of Twitter. Our contribution is at providing deep insight into the cumulative spreading patterns of rumors over time as well as at tracking the precise changes in predictive powers across rumor features. Statistical analysis finds that structural and temporal features distinguish rumors from non-rumors over a long-term window, yet they are not available during the initial propagation phase. In contrast, user and linguistic features are readily available and act as a good indicator during the initial propagation phase. Based on these findings, we suggest a new rumor classification algorithm that achieves competitive accuracy over both short and long time windows. These findings provide new insights for explaining rumor mechanism theories and for identifying features of early rumor detection.

  16. Tuning vibrational mode localization with frequency windowing

    NASA Astrophysics Data System (ADS)

    Cheng, Xiaolu; Talbot, Justin J.; Steele, Ryan P.

    2016-09-01

    Local-mode coordinates have previously been shown to be an effective starting point for anharmonic vibrational spectroscopy calculations. This general approach borrows techniques from localized-orbital machinery in electronic structure theory and generates a new set of spatially localized vibrational modes. These modes exhibit a well-behaved spatial decay of anharmonic mode couplings, which, in turn, allows for a systematic, a priori truncation of couplings and increased computational efficiency. Fully localized modes, however, have been found to lead to unintuitive mixtures of characteristic motions, such as stretches and bends, and accordingly large bilinear couplings. In this work, a very simple, tunable localization frequency window is introduced, in order to realize the transition from normal modes to fully localized modes. Partial localization can be achieved by localizing only pairs of modes within this traveling frequency window, which allows for intuitive interpretation of modes. The optimal window size is suggested to be a few hundreds of wave numbers, based on small- to medium-sized test systems, including water clusters and polypeptides. The new sets of partially localized coordinates retain their spatial coupling decay behavior while providing a reduced number of potential energy evaluations for convergence of anharmonic spectra.

  17. Heating efficiency of multi-walled carbon nanotubes in the first and second biological windows.

    PubMed

    Maestro, Laura Martínez; Haro-González, Patricia; del Rosal, Blanca; Ramiro, Julio; Caamaño, A J; Carrasco, Elisa; Juarranz, Angeles; Sanz-Rodríguez, Francisco; Solé, José García; Jaque, Daniel

    2013-09-07

    Quantum dot based-thermometry, in combination with double beam confocal microscopy and infrared thermal imaging, has been used to investigate the heating efficiency of multi-walled carbon nanotubes (MWCNTs) under optical excitation within the first (808 nm) and second (1090 nm) biological windows as well as in the spectral region separating them (980 nm). It has been found that for the three excitation wavelengths the heating efficiency of MWCNTs (10 nm in diameter and 1.5 μm in length) is close to 50%. Despite this "flat" heating efficiency, we have found that the excitation wavelength is, indeed, critical during in vivo experiments due to the spectral dependence of both tissue absorption and scattering coefficients. It has been concluded that efficiency and selectivity of in vivo photothermal treatments based on MWCNTs are simultaneously optimized when laser irradiation lies within the first or second biological window.

  18. Window Area and Development Drive Spatial Variation in Bird-Window Collisions in an Urban Landscape

    PubMed Central

    Hager, Stephen B.; Cosentino, Bradley J.; McKay, Kelly J.; Monson, Cathleen; Zuurdeeg, Walt; Blevins, Brian

    2013-01-01

    Collisions with windows are an important human-related threat to birds in urban landscapes. However, the proximate drivers of collisions are not well understood, and no study has examined spatial variation in mortality in an urban setting. We hypothesized that the number of fatalities at buildings varies with window area and habitat features that influence avian community structure. In 2010 we documented bird-window collisions (BWCs) and characterized avian community structure at 20 buildings in an urban landscape in northwestern Illinois, USA. For each building and season, we conducted 21 daily surveys for carcasses and nine point count surveys to estimate relative abundance, richness, and diversity. Our sampling design was informed by experimentally estimated carcass persistence times and detection probabilities. We used linear and generalized linear mixed models to evaluate how habitat features influenced community structure and how mortality was affected by window area and factors that correlated with community structure. The most-supported model was consistent for all community indices and included effects of season, development, and distance to vegetated lots. BWCs were related positively to window area and negatively to development. We documented mortalities for 16/72 (22%) species (34 total carcasses) recorded at buildings, and BWCs were greater for juveniles than adults. Based on the most-supported model of BWCs, the median number of annual predicted fatalities at study buildings was 3 (range = 0–52). These results suggest that patchily distributed environmental resources and levels of window area in buildings create spatial variation in BWCs within and among urban areas. Current mortality estimates place little emphasis on spatial variation, which precludes a fundamental understanding of the issue. To focus conservation efforts, we illustrate how knowledge of the structural and environmental factors that influence bird-window collisions can be used

  19. Window area and development drive spatial variation in bird-window collisions in an urban landscape.

    PubMed

    Hager, Stephen B; Cosentino, Bradley J; McKay, Kelly J; Monson, Cathleen; Zuurdeeg, Walt; Blevins, Brian

    2013-01-01

    Collisions with windows are an important human-related threat to birds in urban landscapes. However, the proximate drivers of collisions are not well understood, and no study has examined spatial variation in mortality in an urban setting. We hypothesized that the number of fatalities at buildings varies with window area and habitat features that influence avian community structure. In 2010 we documented bird-window collisions (BWCs) and characterized avian community structure at 20 buildings in an urban landscape in northwestern Illinois, USA. For each building and season, we conducted 21 daily surveys for carcasses and nine point count surveys to estimate relative abundance, richness, and diversity. Our sampling design was informed by experimentally estimated carcass persistence times and detection probabilities. We used linear and generalized linear mixed models to evaluate how habitat features influenced community structure and how mortality was affected by window area and factors that correlated with community structure. The most-supported model was consistent for all community indices and included effects of season, development, and distance to vegetated lots. BWCs were related positively to window area and negatively to development. We documented mortalities for 16/72 (22%) species (34 total carcasses) recorded at buildings, and BWCs were greater for juveniles than adults. Based on the most-supported model of BWCs, the median number of annual predicted fatalities at study buildings was 3 (range = 0-52). These results suggest that patchily distributed environmental resources and levels of window area in buildings create spatial variation in BWCs within and among urban areas. Current mortality estimates place little emphasis on spatial variation, which precludes a fundamental understanding of the issue. To focus conservation efforts, we illustrate how knowledge of the structural and environmental factors that influence bird-window collisions can be used to

  20. Solar absorption surface panel

    DOEpatents

    Santala, Teuvo J.

    1978-01-01

    A composite metal of aluminum and nickel is used to form an economical solar absorption surface for a collector plate wherein an intermetallic compound of the aluminum and nickel provides a surface morphology with high absorptance and relatively low infrared emittance along with good durability.