Thermal stability in the blended lithium manganese oxide – Lithium nickel cobalt manganese oxide cathode materials: An in situ time-resolved X-Ray diffraction and mass spectroscopy study

DOE PAGES

Hu, Enyuan; Bak, Seong Min; Senanayake, Sanjaya D.; ...

2015-03-01

Thermal stabilities of a series of blended LiMn 2O 4(LMO)-LiNi 1/3Co 1/3Mn 1/3O 2 (NCM) cathode materials with different weight ratios were studied by in situ time-resolved X-ray diffraction (XRD) combined with mass spectroscopy in the temperature range of 25°C-580°C under helium atmosphere. Upon heating, the electrochemically delithiated LMO changed into Mn 3O 4 phase at around 250°C. Formation of MnO with rocksalt structure started at 520°C. This observation is in contrast to the previous report for chemically delithiate LMO in air, in which a process of λ-MnO 2 transforming to β-MnO 2 was observed. Oxygen peak was not observedmore » in all cases, presumably as a result of either consumption by the carbon or detection limit. CO 2 profile correlates well with the phase transition and indirectly suggests the oxygen release of the cathode. Introducing NCM into LMO has two effects: first, it makes the high temperature rock-salt phase formation more complicated with more peaks in CO 2 profile due to different MO (M = Ni, Mn, Co) phases; secondly, the onset temperature of CO 2 release is lowered, implying lowered oxygen release temperature. Upon heating, XRD patterns indicate the NCM part reacts first, followed by the LMO part. This confirms the better thermal stability of LMO over NCM.« less

Chromospheric Response during the Precursor and the Main Phase of a B6.4 Flare on 2005 August 20

NASA Astrophysics Data System (ADS)

Awasthi, Arun Kumar; Rudawy, Pawel; Falewicz, Robert; Berlicki, Arkadiusz; Liu, Rui

2018-05-01

Solar flare precursors depict a constrained rate of energy release, in contrast to the imminent rapid energy release, which calls for a different regime of plasma processes to be at play. Due to the subtle emission during the precursor phase, its diagnostics remain delusive, revealing either nonthermal electrons (NTEs) or thermal conduction to be the driver. In this regard, we investigate the chromospheric response during various phases of a B6.4 flare on 2005 August 20. Spatiotemporal investigation of flare ribbon enhancement during the precursor phase, carried out using spectra images recorded in several wavelength positions on the Hα line profile, revealed its delayed response (180 s) compared to the X-ray emission, as well as a sequential increment in the width of the line profile, which are indicative of a slow heating process. However, the energy contained in the Hα emission during the precursor phase can reach as high as 80% of that estimated during the main phase. Additionally, the plasma hydrodynamics during the precursor phase, resulting from the application of a single-loop one-dimensional model, revealed the presence of a power-law extension in the model-generated X-ray spectra, with a flux lower than the RHESSI background. Therefore, our multiwavelength diagnostics and hydrodynamical modeling of the precursor emission indicates the role of a two-stage process. First, reconnection-triggered NTEs, although too small in flux to overcome the observational constraints, thermalize in the upper chromosphere. This leads to the generation of a slow conduction front, which causes plasma heating during the precursor phase.

Validation of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug.

PubMed

Söderlind, Erik; Abrahamsson, Bertil; Erlandsson, Fredrik; Wanke, Christoph; Iordanov, Ventzeslav; von Corswant, Christian

2015-11-10

A clinical study was conducted to validate the in vivo drug release performance of IntelliCap® CR capsules. 12 healthy, male volunteers were administered IntelliCap® CR capsules, filled with metoprolol as a BCS 1 model drug, and programmed to release the drug with 3 different release profiles (2 linear profiles extending over 6h and 14h, respectively, and a pulsed profile with two equal pulses separated by 5h) using a cross-over design. An oral metoprolol solution was included as a reference. Standard bioavailability variables were determined. In vivo drug release-time profiles for the IntelliCap® CR capsules were calculated from the plasma drug concentrations by deconvolution, and they were subsequently compared with the in vitro drug release profiles including assessment of level A in vitro/in vivo correlation (IVIVC). The relative bioavailability for the linear, extended release profiles was about 85% which is similar to other extended release administrations of metoprolol. There was an excellent agreement between the predetermined release profiles and the in vivo release for these two administrations. For IntelliCap® CR capsules programmed to deliver 2 distinct and equal drug pulses, the first pulse was delivered as expected whereas only about half of the second dose was released. Thus, it is concluded that the IntelliCap® system is well suited for the fast and reliable generation of in vivo pharmacokinetic data for extended release drug profiles, e.g. in context of regional drug absorption investigations. For immediate release pulses delivered in the distal GI tract this version of the device appears however less suitable. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of the risk due to release of carbon fiber in civil aircraft accidents, phase 2

NASA Technical Reports Server (NTRS)

Pocinki, L.; Cornell, M. E.; Kaplan, L.

1980-01-01

The risk associated with the potential use of carbon fiber composite material in commercial jet aircraft is investigated. A simulation model developed to generate risk profiles for several airports is described. The risk profiles show the probability that the cost due to accidents in any year exceeds a given amount. The computer model simulates aircraft accidents with fire, release of fibers, their downwind transport and infiltration of buildings, equipment failures, and resulting ecomomic impact. The individual airport results were combined to yield the national risk profile.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, W.; Kan, A.T.; Fu, G.

Neutral organic contaminants commonly reside on the solid portion of soils and sediments. The extent of desorption from these solids determines the fate, reactivity, and toxicity. Numerous researchers have observed that, after an initial exposure of a few days, desorption takes place in two phases, namely, an initial rapid release followed by a long-term resistant phase. Resistant desorption has been highly unpredictable. In this research, the adsorption and desorption of chlorobenzenes, hexachlorobutadiene, and naphthalene have been studied using historically and freshly contaminated bayou sediments from Lake Charles, Louisiana, USA. After an initial release period, both laboratory-spiked and historically contaminated sedimentsmore » from Lake Charles, Louisiana, USA. After an initial release period, both laboratory-spiked and historically contaminated sediments exhibit similar desorption profiles. The simulations compare favorably with previous in situ measurements. All desorption results, both laboratory and field, could reasonably be interpreted using a single irreversible isotherm. Consequences of these results in terms of sediment quality criteria (SQC) are also discussed. Finally, an index of fractional irreversible adsorption is proposed and tested.« less

Application of a biphasic test for characterization of in vitro drug release of immediate release formulations of celecoxib and its relevance to in vivo absorption.

PubMed

Shi, Yi; Gao, Ping; Gong, Yuchuan; Ping, Haili

2010-10-04

A biphasic in vitro test method was used to examine release profiles of a poorly soluble model drug, celecoxib (CEB), from its immediate release formulations. Three formulations of CEB were investigated in this study, including a commercial Celebrex capsule, a solution formulation (containing cosolvent and surfactant) and a supersaturatable self-emulsifying drug delivery system (S-SEDDS). The biphasic test system consisted of an aqueous buffer and a water-immiscible organic solvent (e.g., octanol) with the use of both USP II and IV apparatuses. The aqueous phase provided a nonsink dissolution medium for CEB, while the octanol phase acted as a sink for CEB partitioning. For comparison, CEB concentration-time profiles of these formulations in the aqueous medium under either a sink condition or a nonsink condition were also explored. CEB release profiles of these formulations observed in the aqueous medium from either the sink condition test, the nonsink condition test, or the biphasic test have little relevance to the pharmacokinetic observations (e.g., AUC, C(max)) in human subjects. In contrast, a rank order correlation among the three CEB formulations is obtained between the in vitro AUC values of CEB from the octanol phase up to t = 2 h and the in vivo mean AUC (or C(max)) values. As the biphasic test permits a rapid removal of drug from the aqueous phase by partitioning into the organic phase, the amount of drug in the organic phase represents the amount of drug accumulated in systemic circulation in vivo. This hypothesis provides the scientific rationale for the rank order relationship among these CEB formulations between their CEB concentrations in the organic phase and the relative AUC or C(max). In addition, the biphasic test method permits differentiation and discrimination of key attributes among the three different CEB formulations. This work demonstrates that the biphasic in vitro test method appears to be useful as a tool in evaluating performance of formulations of poorly water-soluble drugs and to provide potential for establishing an in vitro-in vivo relationship.

Simulation of stimuli-triggered release of molecular species from halloysite nanotubes

NASA Astrophysics Data System (ADS)

Elumalai, Divya Narayan; Tully, Joshua; Lvov, Yuri; Derosa, Pedro A.

2016-10-01

A Monte Carlo model is used to study the effect of environmental variables (pH and temperature) on the transport and release of dexamethasone molecules from Halloysite Nanotubes (HNTs) in a dielectric fluid medium. The model used for this study was introduced elsewhere and it is based on basic physics interactions without experimental parameters for these interactions. An intermediate phase between the burst and saturation phase is found and explained. Molecules experience a 1-D diffusion process that is different from the diffusion in the burst phase or the surface diffusion experienced by molecules attached to the wall. It is predicted that this phase exists when the molecule-wall interaction is attractive but not always noticeable in the release profile. In this work, it is shown that an agreement with the experiment better than previously reported is obtained when simulated delivery curves are produced by the weighted average of the release profiles from a collection of HNTs with diameters and lengths distributed according to the experimental sample, highlighting the relevance of HNTs' morphology in the release. HNTs are suitable for environment-triggered release and thus the effect of temperature, molecule zeta potential, and pH is studied. It is observed that for temperatures that significantly differ from room temperature (by 100's of degrees), the release profile changes significantly, increasing the delivery speed at high temperature and reducing that speed at low temperature. Finally, it is observed that as the pH becomes more acidic, both the molecule and inner wall surface become more positive (or less negative) with both eventually becoming positive leading to a repulsive interaction; thus, molecules are pushed out by electrostatic repulsion. On the contrary, as the pH becomes more basic, positive molecules become more positive while the wall becomes less negative, but even at pH 12, the wall remains negative and the interaction is attractive. Changes in pH between different regions may act as a trigger for delivery or as a control in the delivery rate.

Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery.

PubMed

Sharma, Varsha; Anandhakumar, Sundaramurthy; Sasidharan, Manickam

2015-11-01

In this study, we have examined the encapsulation and release of hydrophilic and hydrophobic drugs in self-degrading niosomes as a unique method for anticancer therapy. Niosomes were prepared by amphiphilic self-assembly of Tween 80 and cholesterol through film hydration method. Encapsulation studies with two active molecules curcumin and doxorubicin hydrochloride (Dox) showed that curcumin is supposed to accumulate in the shell whereas Dox accumulates in the inner aqueous core of the niosome. Confocal studies indicated that nile red adsorbs preferentially to the head group of the Tween 80 and forms two separate layers in the shell. It was also seen that the niosomes undergo self-degradation in PBS through a sequential process, forming interconnected pores followed by complete collapse after 1week. The release profile shows two phases: i) initial Dox release in the first two days, followed by ii) curcumin release over 7days. Enhanced (synergistic) cytotoxicity was observed for dual-drug loaded niosomes against HeLa cell lines. Thus these niosomes are shown to offer a promising delivery system for hydrophobic and hydrophilic drugs collectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of ionic complexation on release rate profiles from multiple water-in-oil-in-water (W/O/W) emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; David-Briand, Elisabeth; Anton, Marc; Leal-Calderon, Fernando

2010-07-14

Water-in-oil-in-water (W/O/W) double emulsions were prepared, and the kinetics of release of magnesium ions from the internal to the external water phase was followed. Different chelating agents (phosvitin and gluconate) were used to bind magnesium within the prospect of improving the ion retention in the internal aqueous droplets. Magnesium release was monitored for 1 month of storage, for each formulation, with and without chelation, at two storage temperatures (4 and 25 degrees C). Leakage occurred without film rupturing (coalescence) and was mainly due to entropically driven diffusion/permeation phenomena. The experimental results revealed a clear correlation between the effectiveness of chelating agents to delay the delivery and their binding capacity characterized by the equilibrium affinity constant. The kinetic data (percent released versus time curves) were interpreted within the framework of a kinetic model based on diffusion and taking into account magnesium chelation.

Using NMR chemical shift imaging to monitor swelling and molecular transport in drug-loaded tablets of hydrophobically modified poly(acrylic acid): methodology and effects of polymer (in)solubility.

PubMed

Knöös, Patrik; Topgaard, Daniel; Wahlgren, Marie; Ulvenlund, Stefan; Piculell, Lennart

2013-11-12

A new technique has been developed using NMR chemical shift imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.

Influence of the oil globule fraction on the release rate profiles from multiple W/O/W emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; Monteil, Julien; Anton, Marc; Leal-Calderon, Fernando

2010-06-15

Water-in-oil-in-water (W/O/W) double emulsions were prepared and the kinetics of release of magnesium ions from the internal to the external water phase was investigated as a function of the formulation and the globule volume fraction. All the emulsions were formulated using the same surface-active species (polyglycerol polyricinoleate and sodium caseinate). Also, the internal droplet and oil globule diameters were almost identical for all the systems. Two types of W/O/W emulsions were prepared based either on a synthetic oil (miglyol) or on an edible oil (olive oil). The globule volume fraction varied from 11% to 72%. At constant temperature (T=25 degrees C) and irrespective of the oil type, the percentage of magnesium released was lowered by increasing the globule fraction. In all cases, magnesium leakage occurred without film rupturing (no coalescence). Thus, the experimental data were interpreted within the frame of a model based on diffusion. The rate of release was determined by the permeation coefficient of magnesium across the oil phase and by the binding (chelation) of magnesium by caseinate molecules. The data could be adequately fitted by considering a time-dependant permeation coefficient. The better retention of magnesium at high globule fractions could account for two distinct phenomena: (i) the reduction of the relative volume of the outer phase, and (ii) the attenuation of the permeation coefficient over time induced by interfacial magnesium binding, all the more important than the globule fraction increased. Copyright 2010 Elsevier B.V. All rights reserved.

Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate.

PubMed

Amrutkar, P P; Chaudhari, P D; Patil, S B

2012-01-01

Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions.

PubMed

Learoyd, Tristan P; Burrows, Jane L; French, Eddie; Seville, Peter C

2010-01-01

The sustained delivery of multiple agents to the lung offers potential benefits to patients. This study explores the preparation of highly respirable dual-loaded spray-dried double emulsions. Spray-dried powders were produced from water-in-oil-in-water (w/o/w) double emulsions, containing salbutamol sulphate and/or beclometasone dipropionate in varying phases. The double emulsions contained the drug release modifier polylactide co-glycolide (PLGA 50 : 50) in the intermediate organic phase of the original micro-emulsion and low molecular weight chitosan (Mw<190 kDa: emulsion stabilizer) and leucine (aerosolization enhancer) in the tertiary aqueous phase. Following spray-drying resultant powders were physically characterized: with in vitro aerosolization performance and drug release investigated using a Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. Powders generated were of a respirable size exhibiting emitted doses of over 95% and fine particle fractions of up to 60% of the total loaded dose. Sustained drug release profiles were observed during dissolution for powders containing agents in the primary aqueous and secondary organic phases of the original micro-emulsion; the burst release of agents was witnessed from the tertiary aqueous phase. The novel spray-dried emulsions from this study would be expected to deposit and display sustained release character in the lung.

Development of in vitro-in vivo correlation of parenteral naltrexone loaded polymeric microspheres.

PubMed

Andhariya, Janki V; Shen, Jie; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J

2017-06-10

Establishment of in vitro-in vivo correlations (IVIVCs) for parenteral polymeric microspheres has been very challenging, due to their complex multiphase release characteristics (which is affected by the nature of the drug) as well as the lack of compendial in vitro release testing methods. Previously, a Level A correlation has been established and validated for polymeric microspheres containing risperidone (a practically water insoluble small molecule drug). The objectives of the present study were: 1) to investigate whether a Level A IVIVC can be established for polymeric microspheres containing another small molecule drug with different solubility profiles compared to risperidone; and 2) to determine whether release characteristic differences (bi-phasic vs tri-phasic) between microspheres can affect the development and predictability of IVIVCs. Naltrexone was chosen as the model drug. Three compositionally equivalent formulations of naltrexone microspheres with different release characteristics were prepared using different manufacturing processes. The critical physicochemical properties (such as drug loading, particle size, porosity, and morphology) as well as the in vitro release characteristics of the prepared naltrexone microspheres and the reference-listed drug (Vivitrol®) were determined. The pharmacokinetics of the naltrexone microspheres were investigated using a rabbit model. The obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method, and compared with the in vitro release profiles of the naltrexone microspheres obtained using USP apparatus 4. Level A IVIVCs were established and validated for predictability. The results demonstrated that the developed USP 4 method was capable of detecting manufacturing process related performance changes, and most importantly, predicting the in vivo performance of naltrexone microspheres in the investigated animal model. A critical difference between naltrexone and risperidone loaded microspheres is their respective bi-phasic and tri-phasic release profiles with varying burst release and lag phase. These variations in release profiles affect the development of IVIVCs. Nevertheless, IVIVCs have been established and validated for polymeric microspheres with different release characteristics. Copyright © 2017. Published by Elsevier B.V.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Development and evaluation of perfluorocarbon nanobubbles for apomorphine delivery.

PubMed

Hwang, Tsong-Long; Lin, Yin-Ku; Chi, Chen-Hsien; Huang, Tse-Hung; Fang, Jia-You

2009-10-01

Apomorphine is a dopamine receptor agonist for treating Parkinson's disease. However, its clinical application is limited by its instability and the need for frequent injections. The aim of the present work was to develop acoustically active perfluorocarbon nanobubbles (PNs) for encapsulation of both apomorphine HCl and base forms to circumvent these delivery problems. The PNs were prepared using coconut oil and perfluoropentane as the inner phase, which was emulsified by phospholipids and cholesterol. The morphology, size, zeta potential, and drug release of the PNs were characterized. The particle size ranged from 150 to 380 nm, with differences in the oil or perfluorocarbon ratio in the formulations. Atomic force microscopy confirmed oval- or raisin-shaped particles and a narrow size distribution of these systems (polydispersity index = 0.25-0.28). The stability experimental results indicated that PNs could protect apomorphine from degradation. Evaporation of the PNs at 37 degrees C was also limited. Apomorphine HCl and base in PNs showed retarded and sustained release profiles. Ultrasound imaging confirmed the echogenic activity of PNs developed in this study. The apomorphine HCl release by insonation at 1 MHz showed enhancements of two- to fourfold compared to the non-ultrasound group, illustrating a possible drug-targeting effect. On the contrary, apomorphine base showed a decreased release profile with ultrasound application. Apomorphine-loaded PNs showed promising stability and safety. They were successful in sustaining apomorphine delivery.

In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres and controlled release of progesterone.

PubMed

Turino, Ludmila N; Mariano, Rodolfo N; Mengatto, Luciano N; Luna, Julio A

2015-01-01

One possibility to obtain a higher dose of drug in a lower formulation volume can be by using of saturated quantity of drug in one of the phases of an emulsion. These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer is added to the organic phase of suspoemulsions, these formulations can be used to entrap the drug inside microspheres after in situ precipitation of the polymer-drug-excipients mix. In this work, performance and stability of progesterone suspensions in triacetin as organic phase of suspoemulsions were evaluated. These formulations were compared with O/W emulsions. Mathematical models were used to study in vitro release profiles. The results confirmed that S/O/W systems could be an attractive alternative to O/W formulations for the entrapment of progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based models fit the in vitro release of progesterone from in situ-formed microspheres. For longer release periods, a time-dependent diffusion coefficient was successfully estimated.

The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

PubMed

Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

2015-04-01

For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Calcium modified edible Canna (Canna edulis L) starch for controlled released matrix

NASA Astrophysics Data System (ADS)

Putri, A. P.; Ridwan, M.; Darmawan, T. A.; Darusman, F.; Gadri, A.

2017-07-01

Canna edulis L starch was modified with calcium chloride in order to form controlled released matrix. Present study aim to analyze modified starch characteristic. Four different formulation of ondansetron granules was used to provide dissolution profile of controlled released, two formula consisted of 15% and 30% modified starch, one formula utilized matrix reference standards and the last granules was negative control. Methocel-hydroxypropyl methyl cellulose was used as controlled released matrix reference standards in the third formula. Calcium starch was synthesized in the presence of sodium hydroxide to form gelatinized mass and calcium chloride as the cross linking agent. Physicochemical and dissolution properties of modified starch for controlled released application were investigated. Modified starch has higher swelling index, water solubility and compressibility index. Three of four different formulation of granules provide dissolution profile of controlled released. The profiles indicate granules which employed calcium Canna edulis L starch as matrix are able to resemble controlled drug released profile of matrix reference, however their bigger detain ability lead to lower bioavailability.

[Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets for colon-specific release].

PubMed

Cui, Qi-Hua; Cui, Jing-Hao; Zhang, Jin-Jin

2008-10-01

To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release. In order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties. The formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%. The preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

PubMed

Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

2018-06-14

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.

PubMed

Qiu, Shi; Li, Mingzhong

2015-02-01

The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term ground penetrating radar monitoring of a small volume DNAPL release in a natural groundwater flow field.

PubMed

Hwang, Yong Keun; Endres, Anthony L; Piggott, Scott D; Parker, Beth L

2008-04-04

An earlier field experiment at Canadian Forces Base Borden by Brewster and Annan [Geophysics 59 (1994) 1211] clearly demonstrated the capability of ground penetrating radar (GPR) reflection profiling to detect and monitor the formation of DNAPL layers in the subsurface. Their experiment involved a large volume release (770 L) of tetrachloroethylene into a portion of the sand aquifer that was hydraulically isolated from groundwater flow by sheet pile walls. In this study, we evaluated the ability of GPR profiling to detect and monitor much smaller volume releases (50 L). No subsurface confining structure was used in this experiment; hence, the DNAPL impacted zone was subjected to the natural groundwater flow regime. This condition allowed us to geophysically monitor the DNAPL mass loss over a 66 month period. Reflectivity variations on the GPR profiles were used to infer the presence and evolution of the solvent layers. GPR imaging found significant reflectivity increases due to solvent layer formation during the two week period immediately after the release. These results demonstrated the capacity of GPR profiling for the detection and monitoring of lesser volume DNAPL releases that are more representative of small-scale industrial spills. The GPR imaged solvent layers subsequently reduced in both areal extent and reflectivity after 29 months and almost completely disappeared by the end of the 66 month monitoring period. Total DNAPL mass estimates based on GPR profiling data indicated that the solvent mass was reduced to 34%-36% of its maximum value after 29 months; only 4%-9% of the solvent mass remained in the study area after 66 months. These results are consistent with independent hydrogeological estimates of remaining DNAPL mass based on the downgradient monitoring of the dissolved solvent phase. Hence, we have concluded that the long-term GPR reflectivity changes of the DNAPL layers are likely the result from the dissolution of chlorinated solvents residing in those layers. The long-term monitoring results demonstrated that GPR profiling is a promising non-invasive method for use at DNAPL contaminated sites in sandy aquifers where temporal information about immiscible contaminant mass depletion due to either natural flow or remediation is needed. However, our results also indicated that the GPR signature of older DNAPL impacted zones may not differ greatly from the uncontaminated background if significant mass reduction due to dissolution has occurred.

Development of thermosensitive microgel-loaded cotton fabric for controlled drug release

NASA Astrophysics Data System (ADS)

Sun, Xiao-Zhu; Wang, Xiao; Wu, Jun-Zi; Li, Shu-De

2017-05-01

COS-g-PVCL copolymer was synthesized and infiltrated into CaCO3 particles to prepare thermosensitive porous microgels which exhibited phase transition behavior at the temperature that was similar to the lower critical solution temperature(LCST) of copolymer. The incorporation of microgel to cotton was done by pad-dry-cure method from aqueous microparticle dispersion that contained citric acid as a crosslinking agent. In vitro drug release experiments were performed at two different temperatures (25 and 37 °C) in PBS of pH 7.4 to study its drug release behavior with response to temperature. Due to the shrinkage of microgels, drug release profiles obtained were found to have enhanced release for aloin when the temperature was above LCST than other release conditions. Microgel-loaded fabrics proved to be in vivo biocompatible by skin irritation studies and displayed an obviously high water vapor permeability at 40 °C. The MTT assay showed no obvious cytotoxicity of microgel-loaded cotton against mouse fibroblast cells within 5 days. The results obtained demonstrated the potential use of the thermos-responsive microgel-loaded cotton fabrics as a textile-based drug delivery system for treating sunburn or skin care.

Velocity Profile measurements in two-phase flow using multi-wave sensors

NASA Astrophysics Data System (ADS)

Biddinika, M. K.; Ito, D.; Takahashi, H.; Kikura, H.; Aritomi, M.

2009-02-01

Two-phase flow has been recognized as one of the most important phenomena in fluid dynamics. In addition, gas-liquid two-phase flow appears in various industrial fields such as chemical industries and power generations. In order to clarify the flow structure, some flow parameters have been measured by using many effective measurement techniques. The velocity profile as one of the important flow parameter, has been measured by using ultrasonic velocity profile (UVP) technique. This technique can measure velocity distributions along a measuring line, which is a beam formed by pulse ultrasounds. Furthermore, a multi-wave sensor can measure the velocity profiles of both gas and liquid phase using UVP method. In this study, two types of multi-wave sensors are used. A sensor has cylindrical shape, and another one has square shape. The piezoelectric elements of each sensor have basic frequencies of 8 MHz for liquid phase and 2 MHz for gas phase, separately. The velocity profiles of air-water bubbly flow in a vertical rectangular channel were measured by using these multi-wave sensors, and the validation of the measuring accuracy was performed by the comparison between the velocity profiles measured by two multi-wave sensors.

Co-delivery of ibuprofen and gentamicin from nanoporous anodic titanium dioxide layers.

PubMed

Pawlik, Anna; Jarosz, Magdalena; Syrek, Karolina; Sulka, Grzegorz D

2017-04-01

Although single-drug therapy may prove insufficient in treating bacterial infections or inflammation after orthopaedic surgeries, complex therapy (using both an antibiotic and an anti-inflammatory drug) is thought to address the problem. Among drug delivery systems (DDSs) with prolonged drug release profiles, nanoporous anodic titanium dioxide (ATO) layers on Ti foil are very promising. In the discussed research, ATO samples were synthesized via a three-step anodization process in an ethylene glycol-based electrolyte with fluoride ions. The third step lasted 2, 5 and 10min in order to obtain different thicknesses of nanoporous layers. Annealing the as-prepared amorphous layers at the temperature of 400°C led to obtaining the anatase phase. In this study, water-insoluble ibuprofen and water-soluble gentamicin were used as model drugs. Three different drug loading procedures were applied. The desorption-desorption-diffusion (DDD) model of the drug release was fitted to the experimental data. The effects of crystalline structure, depth of TiO 2 nanopores and loading procedure on the drug release profiles were examined. The duration of the drug release process can be easily altered by changing the drug loading sequence. Water-soluble gentamicin is released for a long period of time if gentamicin is loaded in ATO as the first drug. Additionally, deeper nanopores and anatase phase suppress the initial burst release of drugs. These results confirm that factors such as morphological and crystalline structure of ATO layers, and the procedure of drug loading inside nanopores, allow to alter the drug release performance of nanoporous ATO layers. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, I. John; Murthy, N. Sanjeeva; Kohn, Joachim

2015-10-30

Voclosporin is a highly potent, new cyclosporine -- a derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. It was selected as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic componentmore » is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.« less

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets.

PubMed

Ullah, Majeed; Ullah, Hanif; Murtaza, Ghulam; Mahmood, Qaisar; Hussain, Izhar

2015-01-01

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

PubMed Central

Ullah, Majeed; Ullah, Hanif; Mahmood, Qaisar; Hussain, Izhar

2015-01-01

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID:26380301

Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics

PubMed Central

Tan, Qunyou; Jiang, Rong; Xu, Meiling; Liu, Guodong; Li, Songlin; Zhang, Jingqing

2013-01-01

Background Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine. Methods The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium. Results The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. Conclusion PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors. PMID:23459707

Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics.

PubMed

Tan, Qunyou; Jiang, Rong; Xu, Meiling; Liu, Guodong; Li, Songlin; Zhang, Jingqing

2013-01-01

Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine. The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium. The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors.

Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.

PubMed

Miao, Yanfei; Chen, Guoguang; Ren, Lili; Pingkai, Ouyang

2016-09-01

The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

Polymeric nanoparticles loaded with the 3,5,3'-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics.

PubMed

Dos Santos, Karen C; da Silva, Maria Fatima Gf; Pereira-Filho, Edenir R; Fernandes, Joao B; Polikarpov, Igor; Forim, Moacir R

2012-01-01

This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3'-triiodothyroacetic acid (Triac). A 2(11-6) fractional factorial design and another 2(2) factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment.

Bursting Bubbles and Bilayers

PubMed Central

Wrenn, Steven P.; Dicker, Stephen M.; Small, Eleanor F.; Dan, Nily R.; Mleczko, Michał; Schmitz, Georg; Lewin, Peter A.

2012-01-01

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the “brush” regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly “theranostic” vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery. PMID:23382772

Bursting bubbles and bilayers.

PubMed

Wrenn, Steven P; Dicker, Stephen M; Small, Eleanor F; Dan, Nily R; Mleczko, Michał; Schmitz, Georg; Lewin, Peter A

2012-01-01

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition-- in particular, poly (ethylene glyclol) (PEG)--is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the "brush" regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those--not necessarily involving microubbles--to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly "theranostic" vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.

Microphase separation in solid lipid dosage forms as the cause of drug release instability.

PubMed

Lopes, Diogo Gomes; Koutsamanis, Ioannis; Becker, Karin; Scheibelhofer, Otto; Laggner, Peter; Haack, Detlev; Stehr, Michael; Zimmer, Andreas; Salar-Behzadi, Sharareh

2017-01-30

Although lipid excipients are of increasing interest for development of taste-masked and modified release formulations, the drug release instability and the lack of mechanistic understanding in that regard still prevent their larger-scale application. In this work, we investigated the physical stability of a binary (tripalmitin/polysorbate 65) lipid coating formulation with a known stable polymorphism. The coating composition was characterized using DSC to construct the phase diagram of binary system and polarized light microscopy to display the microstructure organization. The water uptake and the erosion of slabs cast from the coating formulations were investigated post-production and after storage. Subsequently, N-acetylcysteine particles were coated with the selected formulations and the drug release stability was investigated. Additionally, microstructure characterization was performed via SEM and X-ray diffraction. The drug release instability was explained by polysorbate 65 and tripalmitin phase growth during storage, especially at 40°C, suggesting that polysorbate 65 can leak out of tripalmitin spherulitic structures, creating lipophilic and impermeable tripalmitin regions. The growth of polysorbate 65 phase leads to larger hydrophilic channels with reduced tortuosity. This work indicates that for obtaining stable drug release profiles from advanced lipid formulations, microphase separation should be prevented during storage. Copyright © 2016 Elsevier B.V. All rights reserved.

High-pressure phase transition in silicon carbide under shock loading using ultrafast x-ray diffraction

NASA Astrophysics Data System (ADS)

Tracy, S. J.; Smith, R. F.; Wicks, J. K.; Fratanduono, D. E.; Gleason, A. E.; Bolme, C.; Speziale, S.; Appel, K.; Prakapenka, V. B.; Fernandez Panella, A.; Lee, H. J.; MacKinnon, A.; Eggert, J.; Duffy, T. S.

2017-12-01

The behavior of silicon carbide (SiC) under shock loading was investigated through a series of time-resolved pump-probe x-ray diffraction (XRD) measurements. SiC is found at impact sites and has been put forward as a possible constituent in the proposed class of extra-solar planets known as carbon planets. Previous studies have used wave profile measurements to identify a phase transition under shock loading near 1 Mbar, but crystal structure information was not obtained. We have carried out an in situ XRD study of shock-compressed SiC using the Matter in Extreme Conditions instrument of the Linac Coherent Light Source. The femtosecond time resolution of the x-ray free electron laser allows for the determination of time-dependent atomic arrangements during shock loading and release. Two high-powered lasers were used to generate ablation-driven compression waves in the samples. Time scans were performed using the same drive conditions and nominally identical targets. For each shot in a scan, XRD data was collected at a different probe time after the shock had entered the SiC. Probe times extended up to 40 ns after release. Scans were carried out for peak pressures of 120 and 185 GPa. Our results demonstrate that SiC transforms directly from the ambient tetrahedrally-coordinated phase to the octahedral B1 structure on the nanosecond timescale of laser-drive experiments and reverts to the tetrahedrally coordinated ambient phase within nanoseconds of release. The data collected at 120 GPa exhibit diffraction peaks from both compressed ambient phase and transformed B1 phase, while the data at 185 GPa show a complete transformation to the B1 phase. Densities determined from XRD peaks are in agreement with an extrapolation of previous continuum data as well as theoretical predictions. Additionally, a high degree of texture was retained in both the high-pressure phase as well as on back transformation. Two-dimensional fits to the XRD data reveal details of the orientational relationships between the low- and high-pressure phases that can be interpreted to provide information about transformation pathways between tetrahedral and octahedral coordination structures. We acknowledge support for this work from SLAC National Accelerator Laboratory, Lawrence Livermore National Laboratory, and Los Alamos National Laboratory.

Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

PubMed

Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

2014-01-02

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights reserved.

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

PubMed

Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet

PubMed Central

Bhalekar, M. R.; Madgulkar, A. R.; Sheladiya, D. D.; Kshirsagar, S. J.; Wable, N. D.; Desale, S. S.

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 32 full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X1) and bees wax (X2) were selected as independent variables and release after 12 h and time required for 50% (t50) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t50 but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings. PMID:20046773

Effect of alginate composition on profile release and characteristics of chitosan-alginate microparticles loaded with mangosteen extract

NASA Astrophysics Data System (ADS)

Mulia, Kamarza; Halimah, Nur; Krisanti, Elsa

2017-03-01

Preparation of mangostin-loaded chitosan-alginate microparticles, chemical and physical characterization of the particles, and mangostin release profiles, are described herein. Mangostin rich fraction was obtained from Garcinia mangostana L. pericarp by extraction followed by fractionation. Mangostin-loaded chitosan-alginate microparticles were prepared by ionic gelation method using tripolyphosphate as the linking agent and various concentration of alginate. Mangostin was effectively loaded in all microparticle formulations, resulting in ˜97% encapsulation efficiencies. The loading of mangostin and the in-vitro release profiles in simulated gastrointestinal fluids were affected by the chitosan to alginate ratios used in the preparation of the microparticles. Increased alginate concentration resulted in lowered release of mangostin from microparticles immersed in simulated gastric fluid (pH 1.2) up to two hours. Low release of mangostin in acidic fluid but high release in simulated colon fluid, indicated that the chitosan-alginate microparticles are prospective carrier for extended release of active compound in gastrointestinal system.

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Different magnesium release profiles from W/O/W emulsions based on crystallized oils.

PubMed

Herzi, Sameh; Essafi, Wafa

2018-01-01

Water-in-oil-in-water (W/O/W) double emulsions based on crystallized oils were prepared and the release kinetics of magnesium ions from the internal to the external aqueous phase was investigated at T=4°C, for different crystallized lipophilic matrices. All the emulsions were formulated using the same surface-active species, namely polyglycerol polyricinoleate (oil-soluble) and sodium caseinate (water-soluble). The external aqueous phase was a lactose or glucose solution at approximately the same osmotic pressure as that of the inner droplets, in order to avoid osmotic water transfer phenomena. We investigated two types of crystallized lipophilic systems: one based on blends of cocoa butter and miglyol oil, exploring a solid fat content from 0 to 90% and the other system based on milk fat fractions for which the solid fat content varies between 54 and 86%. For double emulsions based on cocoa butter/miglyol oil, the rate of magnesium release was gradually lowered by increasing the % of fat crystals i.e. cocoa butter, in agreement with a diffusion/permeation mechanism. However for double emulsions based on milk fat fractions, the rate of magnesium release was independent of the % of fat crystals and remains the one at t=0. This difference in diffusion patterns, although the solid content is of the same order, suggests a different distribution of fat crystals within the double globules: a continuous fat network acting as a physical barrier for the diffusion of magnesium for double emulsions based on cocoa butter/miglyol oil and double globule/water interfacial distribution for milk fat fractions based double emulsions, through the formation of a crystalline shell allowing an effective protection of the double globules against diffusion of magnesium to the external aqueous phase. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic analysis of modified-release metoprolol formulations: An interspecies comparison.

PubMed

De Thaye, Elien; Vervaeck, Anouk; Marostica, Eleonora; Remon, Jean Paul; Van Bocxlaer, Jan; Vervaet, Chris; Vermeulen, An

2017-01-15

In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling, and two commercially available formulations, ZOK-ZID ® (reservoir) and Slow-Lopresor ® (matrix) in both New Zealand White rabbits and Beagle dogs, using a population pharmacokinetic analysis approach. The aim of this study was to compare the in vivo pharmacokinetic (PK) profiles of different formulations based on metoprolol, a selective adrenergic β 1 -receptor antagonist, in dogs and rabbits and to contrast the observed differences. To that end, metoprolol (50 to 200mg) was administered to 6 Beagle dogs and 6 New Zealand White rabbits as a single intravenous (IV) bolus injection and to 8 dogs and 6 rabbits as an oral modified release formulation. To derive pharmacokinetic parameters from the data, a non-linear mixed-effects model was developed using NONMEM ® where the contribution of observations below the limit of detection (BDL, below detection limit) to the parameter estimates was taken into account in the parameter estimation procedure. In both species and for the three modified release formulations, different absorption models were tested to describe the PK of metoprolol following oral dosing. In Beagle dogs, plasma concentration-time profiles were best described using a sequential zero- and first-order absorption model. In rabbits though, the absorption phase was best described using a first-order process only. In both species, the reservoir formulation ZOK-ZID ® was behaving quite similarly. In contrast, the absorption properties of both matrix formulations were rather different between species. This study indicates that the PK of the reservoir formulation is similar in both species, even after accounting for the almost completely missed absorption phase in rabbits. The insights gained further illustrate that rabbits are not very well suited to study the PK of the current matrix formulations in view of their less optimal prolonged release characteristics and the resulting fast decline in metoprolol plasma levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Two complementary reversed-phase separations for comprehensive coverage of the semipolar and nonpolar metabolome.

PubMed

Naser, Fuad J; Mahieu, Nathaniel G; Wang, Lingjue; Spalding, Jonathan L; Johnson, Stephen L; Patti, Gary J

2018-02-01

Although it is common in untargeted metabolomics to apply reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) methods that have been systematically optimized for lipids and central carbon metabolites, here we show that these established protocols provide poor coverage of semipolar metabolites because of inadequate retention. Our objective was to develop an RPLC approach that improved detection of these metabolites without sacrificing lipid coverage. We initially evaluated columns recently released by Waters under the CORTECS line by analyzing 47 small-molecule standards that evenly span the nonpolar and semipolar ranges. An RPLC method commonly used in untargeted metabolomics was considered a benchmarking reference. We found that highly nonpolar and semipolar metabolites cannot be reliably profiled with any single method because of retention and solubility limitations of the injection solvent. Instead, we optimized a multiplexed approach using the CORTECS T3 column to analyze semipolar compounds and the CORTECS C 8 column to analyze lipids. Strikingly, we determined that combining these methods allowed detection of 41 of the total 47 standards, whereas our reference RPLC method detected only 10 of the 47 standards. We then applied credentialing to compare method performance at the comprehensive scale. The tandem method showed more than a fivefold increase in credentialing coverage relative to our RPLC benchmark. Our results demonstrate that comprehensive coverage of metabolites amenable to reversed-phase separation necessitates two reconstitution solvents and chromatographic methods. Thus, we suggest complementing HILIC methods with a dual T3 and C 8 RPLC approach to increase coverage of semipolar metabolites and lipids for untargeted metabolomics. Graphical abstract Analysis of semipolar and nonpolar metabolites necessitates two reversed-phase chromatography (RPLC) methods, which extend metabolome coverage more than fivefold for untargeted profiling. HILIC hydrophilic interaction liquid chromatography.

Preparation and characterization of silica xerogels as carriers for drugs.

PubMed

Czarnobaj, K

2008-11-01

The aim of the present study was to utilize the sol-gel method to synthesize different forms of xerogel matrices for drugs and to investigate how the synthesis conditions and solubility of drugs influence the change of the profile of drug release and the structure of the matrices. Silica xerogels doped with drugs were prepared by the sol-gel method from a hydrolyzed tetraethoxysilane (TEOS) solution containing two model compounds: diclofenac diethylamine, (DD)--a water-soluble drug or ibuprofen, (IB)--a water insoluble drug. Two procedures were used for the synthesis of sol-gel derived materials: one-step procedure (the sol-gel reaction was carried out under acidic or basic conditions) and the two-step procedure (first, hydrolysis of TEOS was carried out under acidic conditions, and then condensation of silanol groups was carried out under basic conditions) in order to obtain samples with altered microstructures. In vitro release studies of drugs revealed a similar release profile in two steps: an initial diffusion-controlled release followed by a slower release rate. In all the cases studied, the released amount of DD was higher and the released time was shorter compared with IB for the same type of matrices. The released amount of drugs from two-step prepared xerogels was always lower than that from one-step base-catalyzed xerogels. One-step acid-catalyzed xerogels proved unsuitable as the carriers for the examined drugs.

Interplanetary propagation of flare-associated energetic particles

NASA Technical Reports Server (NTRS)

Masung, L. L.; Earl, J. A.

1978-01-01

A propagation model which combines a Gaussian profile for particle release from the sun, with interplanetary particle densities predicted by focused diffusion, was proposed to explain the propagation history of flare associated energetic particles. This model, which depends on only two parameters, successfully describes the time-intensity profiles of 30 proton and electron events originating from the western hemisphere of the sun. Generally, particles are released from the sun over a finite interval. In almost all events, particle release begins at the time of flare acceleration.

Influence of Polymer Type on the Physical Properties and Release Profile of Papaverine Hydrochloride From Hard Gelatin Capsules.

PubMed

Polski, Andrzej; Iwaniak, Karol; Kasperek, Regina; Modrzewska, Joanna; Sobótka-Polska, Karolina; Sławińska, Karolina; Poleszak, Ewa

2015-01-01

The capsule is one of the most important solid dosage forms in the pharmaceutical industry. It is easier and faster to produce than a tablet, because it requires fewer excipients. Generally, capsules are easy to swallow and mask any unpleasant taste of the substances used while their release profiles can be easily modified. Papaverine hydrochloride was used as a model substance to show different release profiles using different excipients. The main aim of the study was to analyze the impact of using different polymers on the release profile of papaverine hydrochloride from hard gelatin capsules. Six series of hard gelatin capsules containing papaverine hydrochloride as a model drug and different excipients were made. Then, the angle of repose, flow rate, mass flow rate and volume flow rate of the powders used for capsule production were analyzed. The uniform weight and disintegration time of the capsules were studied. The dissolution study was performed in a basket apparatus, while the amount of papaverine hydrochloride released was determined spectrophotometrically at 251 nm. Only one formula of powder had satisfactory flow properties, while all formulas had good Hausner ratios. The best properties were from powder containing polyvinylpyrrolidone 10k. The disintegration time of capsules varied from 1:30 min to 2:00 min. As required by Polish Pharmacopoeia X, 80% of the active substance in all cases was released within 15 minutes. The capsules with polyvinylpyrrolidone 10k were characterized by the longest release. On the other hand, capsules containing microcrystalline cellulose had the fastest release profile. Using 10% of different polymers, without changing the other excipients, had a significant impact on the physical properties of the powders and papaverine hydrochloride release profile. The two most preferred capsule formulations contained either polyvinylpyrrolidone 10k or microcrystalline cellulose.

Release profile and stability evaluation of optimized chitosan/alginate nanoparticles as EGFR antisense vector

PubMed Central

Azizi, Ebrahim; Namazi, Alireza; Haririan, Ismaeil; Fouladdel, Shamileh; Khoshayand, Mohammad R; Shotorbani, Parisa Y; Nomani, Alireza; Gazori, Taraneh

2010-01-01

Chitosan/alginate nanoparticles which had been optimized in our previous study using two different N/P ratios were chosen and their ability to release epidermal growth factor receptor (EGFR) antisense was investigated. In addition, the stability of these nanoparticles in aqueous medium and after freeze-drying was investigated. In the case of both N/P ratios (5, 25), nanoparticles started releasing EGFR antisense as soon as they were exposed to the medium and the release lasted for approximately 50 hours. Nanoparticle size, shape, zeta potential, and release profile did not show any significant change after the freeze-drying process (followed by reswelling). The nanoparticles were reswellable again after freeze-drying in phosphate buffer with a pH of 7.4 over a period of six hours. Agarose gel electrophoresis of the nanoparticles with the two different N/P ratios showed that these nanoparticles could protect EGFR antisense molecules for six hours. PMID:20957167

Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen.

PubMed

Abrego, Guadalupe; Alvarado, Helen L; Egea, Maria A; Gonzalez-Mira, Elizabeth; Calpena, Ana C; Garcia, Maria L

2014-10-01

Pranoprofen (PF)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were optimized and characterized as a means of exploring novel formulations to improve the biopharmaceutical profile of this drug. These systems were prepared using the solvent displacement technique, with polyvinyl alcohol (PVA) as a stabilizer. A factorial design was applied to study the influence of several factors (the pH of the aqueous phase and the stabilizer, polymer and drug concentrations) on the physicochemical properties of the NPs. After optimization, the study was performed at two different aqueous phase pH values (4.50 and 5.50), two concentrations of PF (1.00 and 1.50 mg/mL), three of PVA (5, 10, and 25 mg/mL), and two of PLGA (9.00 and 9.50 mg/mL). These conditions produced NPs of a size appropriate particle size for ocular administration (around 350 nm) and high entrapment efficiency (80%). To improve their stability, the optimized NPs were lyophilized. X-ray, FTIR, and differential scanning calorimetry analysis confirmed the drug was dispersed inside the particles. The release profiles of PF from the primary nanosuspensions and rehydrated freeze-dried NPs were similar and exhibited a sustained drug delivery pattern. The ocular tolerance was assessed by an HET-CAM test. No signs of ocular irritancy were detected (score 0). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

PubMed

Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

2018-01-01

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release profiles were dissimilar. The correlation coefficients (R2) of IVIVC were all above 0.95 and the slopes were all between 0.9564 and 1.1868 in spite of fitted model and microsphere formulation. An in vitro accelerated release method of risperidone microspheres with good IVIVC was established in this paper and this accelerated release method was supposed to have great potential in both in vivo performance prediction and quality control for risperidone loaded PLGA microspheres. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-beta-cyclodextrin.

PubMed

Trapani, Giuseppe; Lopedota, Angela; Boghetich, Giancarlo; Latrofa, Andrea; Franco, Massimo; Sanna, Enrico; Liso, Gaetano

2003-12-11

The goal of this study was to design a prolonged release system of the hypnotic agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone or in the presence of HP-beta-CD was encapsulated in microparticles constituted by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug release from these systems was evaluated. ZP alone-loaded microparticles were prepared by the classical O/W emulsion-solvent evaporation method. Conversely, ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion-solvent evaporation method following two different procedures (i.e. A and B). Following procedure A, the previously produced ZP/HP-beta-CD solid complex was added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was added to the aqueous phase and ZP to the organic phase. The resulting microparticles were characterized about morphology, size, encapsulation efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is in an essentially amorphous state within the microparticles. The release profiles of ZP from microparticles were in general biphasic, being characterized by an initial burst effect and a subsequent slow ZP release. It resulted that co-encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release from the corresponding microparticles was protracted. Moreover, in a preliminary pharmacological screening, the ataxic activity in rats was investigated and it was found that intragastric administration of the ZP/HP-beta-CD/PLGA microparticles prepared according to procedure B produced the same ataxic induction time as the one induced by the currently used formulation Stilnox. Interestingly moreover, there was a longer ataxic lasting and a lower intensity of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min following the administration. However, a need for further pharmacokinetic and pharmacodynamic studies resulted to fully evaluate the utility of this last formulation for the sustained delivery of ZP.

Snow instability evaluation: calculating the skier-induced stress in a multi-layered snowpack

NASA Astrophysics Data System (ADS)

Monti, Fabiano; Gaume, Johan; van Herwijnen, Alec; Schweizer, Jürg

2016-03-01

The process of dry-snow slab avalanche formation can be divided into two phases: failure initiation and crack propagation. Several approaches tried to quantify slab avalanche release probability in terms of failure initiation based on shear stress and strength. Though it is known that both the properties of the weak layer and the slab play a major role in avalanche release, most previous approaches only considered slab properties in terms of slab depth, average density and skier penetration. For example, for the skier stability index, the additional stress (e.g. due to a skier) at the depth of the weak layer is calculated by assuming that the snow cover can be considered a semi-infinite, elastic, half-space. We suggest a new approach based on a simplification of the multi-layered elasticity theory in order to easily compute the additional stress due to a skier at the depth of the weak layer, taking into account the layering of the snow slab and the substratum. We first tested the proposed approach on simplified snow profiles, then on manually observed snow profiles including a stability test and, finally, on simulated snow profiles. Our simple approach reproduced the additional stress obtained by finite element simulations for the simplified profiles well - except that the sequence of layering in the slab cannot be replicated. Once implemented into the classical skier stability index and applied to manually observed snow profiles classified into different stability classes, the classification accuracy improved with the new approach. Finally, we implemented the refined skier stability index into the 1-D snow cover model SNOWPACK. The two study cases presented in this paper showed promising results even though further verification is still needed. In the future, we intend to implement the proposed approach for describing skier-induced stress within a multi-layered snowpack into more complex models which take into account not only failure initiation but also crack propagation.

Snow instability evaluation: calculating the skier-induced stress in a multi-layered snowpack

NASA Astrophysics Data System (ADS)

Monti, F.; Gaume, J.; van Herwijnen, A.; Schweizer, J.

2015-08-01

The process of dry-snow slab avalanche formation can be divided into two phases: failure initiation and crack propagation. Several approaches tried to quantify slab avalanche release probability in terms of failure initiation based on shear stress and strength. Though it is known that both the properties of the weak layer and the slab play a major role in avalanche release, most previous approaches only considered slab properties in terms of slab depth, average density and skier penetration. For example, for the skier stability index, the additional stress (e.g. due to a skier) at the depth of the weak layer is calculated by assuming that the snow cover can be considered a semi-infinite, elastic half-space. We suggest a new approach based on a simplification of the multi-layered elasticity theory in order to easily compute the additional stress due to a skier at the depth of the weak layer taking into account the layering of the snow slab and the substratum. We first tested the proposed approach on simplified snow profiles, then on manually observed snow profiles including a stability test and, finally, on simulated snow profiles. Our simple approach well reproduced the additional stress obtained by finite element simulations for the simplified profiles - except that the sequence of layering in the slab cannot be replicated. Once implemented into the classical skier stability index and applied to manually observed snow profiles classified into different stability classes, the classification accuracy improved with the new approach. Finally, we implemented the refined skier stability index into the 1-D snow cover model SNOWPACK. For the two study cases presented in this paper, this approach showed promising results even though further verification is still needed. In the future, we intend to implement the proposed approach for describing skier-induced stress within a multi-layered snowpack into more complex models which take into account not only failure initiation but also crack propagation.

Gonadotropin-releasing hormone antagonist in the management of prostate cancer.

PubMed

Debruyne, Frans M J

2004-01-01

Luteinizing hormone-releasing hormone (LHRH) agonist therapy to induce medical castration has become the most common form of hormonal therapy for advanced and metastatic prostate cancer. When treatment is started, LHRH agonists initially stimulate the release of LH, causing a surge in serum testosterone that can precipitate a "flare" phenomenon or worsening of disease, particularly in patients with bone metastatic disease. Gonadotropin-releasing hormone (GnRH) receptor antagonism represents a newer approach to medical castration. Abarelix is a pure GnRH receptor antagonist that is devoid of any LHRH agonist activity. Results from 1 phase II and 3 phase III clinical trials demonstrate that abarelix produces medical castration more quickly and without causing testosterone surge, as compared with LHRH agonists with or without a nonsteroidal antagonist. The safety profile in terms of adverse events is comparable between the 2 types of treatment, but the lack of testosterone surge with abarelix might confer a safety advantage by abolishing the risk of a disease flare.

Another Look at the Draft Mil-Std-1540E Unit Random Vibration Test Requirements

NASA Astrophysics Data System (ADS)

Perl, E.; Peterson, A. J..; Davis, D.

2012-07-01

The draft Mil-Std-1540E has been updated to reflect lessons learned since its publication as an SMC Standard in 2008, [1], and an earlier Aerospace Corporation Technical Report released in 2006, [2]. This paper discusses the technical rationale supporting some of the unit random vibration test requirements to provide better insight into their derivation and application to programs. It is intended that these requirements be tailored for each program to reflect the customer risk profile. Several tailoring options are provided and a two phase test strategy is discussed to highlight its applicability to utilizing heritage hardware in new applications.

Development of soy lecithin based novel self-assembled emulsion hydrogels.

PubMed

Singh, Vinay K; Pandey, Preeti M; Agarwal, Tarun; Kumar, Dilip; Banerjee, Indranil; Anis, Arfat; Pal, Kunal

2015-03-01

The current study reports the development and characterization of soy lecithin based novel self-assembled emulsion hydrogels. Sesame oil was used as the representative oil phase. Emulsion gels were formed when the concentration of soy lecithin was >40% w/w. Metronidazole was used as the model drug for the drug release and the antimicrobial tests. Microscopic study showed the apolar dispersed phase in an aqueous continuum phase, suggesting the formation of emulsion hydrogels. FTIR study indicated the formation of intermolecular hydrogen bonding, whereas, the XRD study indicated predominantly amorphous nature of the emulsion gels. Composition dependent mechanical and drug release properties of the emulsion gels were observed. In-depth analyses of the mechanical studies were done using Ostwald-de Waele power-law, Kohlrausch and Weichert models, whereas, the drug release profiles were modeled using Korsmeyer-Peppas and Peppas-Sahlin models. The mechanical analyses indicated viscoelastic nature of the emulsion gels. The release of the drug from the emulsion gels was diffusion mediated. The drug loaded emulsion gels showed good antimicrobial activity. The biocompatibility test using HaCaT cells (human keratinocytes) suggested biocompatibility of the emulsion gels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Soil moisture profile variability in land-vegetation- atmosphere continuum

NASA Astrophysics Data System (ADS)

Wu, Wanru

Soil moisture is of critical importance to the physical processes governing energy and water exchanges at the land-air boundary. With respect to the exchange of water mass, soil moisture controls the response of the land surface to atmospheric forcing and determines the partitioning of precipitation into infiltration and runoff. Meanwhile, the soil acts as a reservoir for the storage of liquid water and slow release of water vapor into the atmosphere. The major motivation of the study is that the soil moisture profile is thought to make a substantial contribution to the climate variability through two-way interactions between the land-surface and the atmosphere in the coupled ocean-atmosphere-land climate system. The characteristics of soil moisture variability with soil depth may be important in affecting the atmosphere. The natural variability of soil moisture profile is demonstrated using observations. The 16-year field observational data of soil moisture with 11-layer (top 2.0 meters) measured soil depths over Illinois are analyzed and used to identify and quantify the soil moisture profile variability, where the atmospheric forcing (precipitation) anomaly propagates down through the land-branch of the hydrological cycle with amplitude damping, phase shift, and increasing persistence. Detailed statistical data analyses, which include application of the periodogram method, the wavelet method and the band-pass filter, are made of the variations of soil moisture profile and concurrently measured precipitation for comparison. Cross-spectral analysis is performed to obtain the coherence pattern and phase correlation of two time series for phase shift and amplitude damping calculation. A composite of the drought events during this time period is analyzed and compared with the normal (non-drought) case. A multi-layer land surface model is applied for modeling the soil moisture profile variability characteristics and investigating the underlying mechanisms. Numerical experiments are conducted to examine the impacts of some potential controlling factors, which include atmospheric forcing (periodic and pulse) at the upper boundary, the initial soil moisture profile, the relative root abundance and the soil texture, on the variability of soil moisture profile and the corresponding evapotranspiration. Similar statistical data analyses are performed for the experimental data. Observations from the First International Satellite Land Surface Climatological Project (ISLSCP) Field Experiment (FIFE) are analyzed and used for the testing of model. The integration of the observational and modeling approaches makes it possible to better understand the mechanisms by which the soil moisture profile variability is generated with phase shift, fluctuation amplitude damping and low-pass frequency filtering with soil depth, to improve the strategies of parameterizations in land surface schemes, and furthermore, to assess its contribution to climate variability.

Release of DNA from polyelectrolyte multilayers fabricated using 'charge-shifting' cationic polymers: tunable temporal control and sequential, multi-agent release.

PubMed

Sun, Bin; Lynn, David M

2010-11-20

We report an approach to the design of multilayered polyelectrolyte thin films (or 'polyelectrolyte multilayers', PEMs) that can be used to provide tunable control over the release of plasmid DNA (or multiple different DNA constructs) from film-coated surfaces. Our approach is based upon methods for the layer-by-layer assembly of DNA-containing thin films, and exploits the properties of a new class of cationic 'charge-shifting' polymers (amine functionalized polymers that undergo gradual changes in net charge upon side chain ester hydrolysis) to provide control over the rates at which these films erode and release DNA. We synthesized two 'charge-shifting' polymers (polymers 1 and 2) containing different side chain structures by ring-opening reactions of poly(2-alkenyl azlactone)s with two different tertiary amine functionalized alcohols (3-dimethylamino-1-propanol and 2-dimethylaminoethanol, respectively). Subsequent characterization revealed large changes in the rates of side chain ester hydrolysis for these two polymers; whereas the half-life for the hydrolysis of the esters in polymer 1 was ~200 days, the half-life for polymer 2 was ~6 days. We demonstrate that these large differences in side chain hydrolysis make possible the design of PEMs that erode and promote the surface-mediated release of DNA either rapidly (e.g., over ~3 days for films fabricated using polymer 2) or slowly (e.g., over ~1 month for films fabricated using polymer 1). We demonstrate further that it is possible to design films with release profiles that are intermediate to these two extremes by fabricating films using solutions containing different mixtures of these two polymers. This approach can thus expand the usefulness of these two polymers and achieve a broader range of DNA release profiles without the need to synthesize polymers with new structures or properties. Finally, we demonstrate that polymers 1 and 2 can be used to fabricate multilayered films with hierarchical structures that promote the sequential release of two different DNA constructs with separate and distinct release profiles (e.g., the release of a first construct over a period of ~3 days, followed by the sustained release of a second for a period of ~70 days). With further development, this approach could contribute to the design of functional thin films and surface coatings that provide sophisticated control over the timing and the order of the release of two or more DNA constructs (or other agents) of interest in a range of biomedical contexts. Copyright © 2010 Elsevier B.V. All rights reserved.

Imaging height fluctuations in free-standing graphene membranes

NASA Astrophysics Data System (ADS)

Dorsey, Kyle; Miskin, Marc; Barnard, Arthur; Rose, Peter; Cohen, Itai; McEuen, Paul

We present a technique based on multi-wavelength interference microscopy to measure the heights of observed ripples in free-standing graphene membranes. Graphene membranes released from a transparent substrate produce interference fringes when viewed in the reflection mode of an inverted microscope(Blees et. al. Nature 524 (7564): 204-207 (2015)). The fringes correspond to corrugation of the membrane as it floats near an interface. A single set of fringes is insufficient to uniquely determine the height profile, as a given fringe spacing can correspond to an increase or decrease in height by λ / 2 . Imaging at multiple wavelengths resolves the ambiguities in phase, and enables unique determination of the height profile of the membrane (Schilling et. al.Phys. Rev. E, 69:021901, 2004). We utilize this technique to map out the height fluctuations in free-standing graphene membranes to answer questions about fundamental mechanical properties of two-dimensional materials.

In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

PubMed Central

Stallmann, Hein P; Faber, Chris; Bronckers, Antonius LJJ; Nieuw Amerongen, Arie V; Wuisman, Paul IJM

2006-01-01

Background Polymethyl-methacrylate (PMMA) beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days), the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days). The relative release of all cements (36–85%) and granules (30–62%) was higher than previously reported for injectable PMMA-cements (up to 17%) and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained) may be achieved. PMID:16504140

Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings

PubMed Central

Shen, Jie; Burgess, Diane J.

2011-01-01

Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under “real-time” and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to “real-time” conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict “real-time” release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under “real-time” and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. PMID:22016033

Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

PubMed

Shen, Jie; Burgess, Diane J

2012-01-17

Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

PubMed

Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

2015-09-01

Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

The in vitro antibiotic release from anti-washout apatite cement using chitosan.

PubMed

Takechi, Masaaki; Miyamoto, Youji; Momota, Yukihiro; Yuasa, Tetsuya; Tatehara, Seikou; Nagayama, Masaru; Ishikawa, Kunio; Suzuki, Kazuomi

2002-10-01

The in vitro antibiotic release from anti-washout apatite cement using chitosan (aw-AC(chi)) was investigated in a preliminary evaluation. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder phase aw-AC(chi) at up to 10%. The setting times were measured for aw-AC(chi) containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug release profile, set aw-AC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The setting time was prolonged slightly with the addition of flomoxef sodium. The difference at 10% flomoxef sodium (0% vs. 10%) was not significant (p>0.05), and can be negligible in clinic. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-AC(chi) was reduced, even after 24 h, when the aw-AC(chi) contained flomoxef sodium at 8% or more. The flomoxef sodium release from aw-AC(chi) showed the typical profile observed in skeleton type drug delivery system (DDS). Changing the concentration of chitosan can control the rate of drug release from aw-AC. Therefore, we conclude that aw-AC(chi) is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease.

PubMed

Gareb, Bahez; Eissens, Anko C; Kosterink, Jos G W; Frijlink, Hendrik W

2016-06-01

Ulcerative colitis (UC) and Crohn's disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient's response. The aim of this study was to develop a zero-order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse® coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX®-mesalazine and MMX®-budesonide. Lag-time, release rate (k0), completeness of release, and zero-order correlation coefficient (R(2)0) could be manipulated by varying ColoPulse® coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250min (simulated ileum targeted), a linear release profile (mesalazine R(2)0=0.9002; budesonide R(2)0=0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX®-mesalazine had a linear (R(2)0=0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210min), assuring simulated ileum specificity. Remarkably, MMX®-budesonide lag-time was 480min and release was only 7% with a linear character (R(2)0=0.9906). The in vitro results suggest that MMX®-budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

PubMed

Moghimipour, Eskandar; Rezaei, Mohsen; Kouchak, Maryam; Fatahiasl, Jafar; Angali, Kambiz Ahmadi; Ramezani, Zahra; Amini, Mohsen; Dorkoosh, Farid Abedin; Handali, Somayeh

2018-05-01

The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

An in situ-forming phospholipid-based phase transition gel prolongs the duration of local anesthesia for ropivacaine with minimal toxicity.

PubMed

Li, Hanmei; Liu, Tao; Zhu, Yuxuan; Fu, Qiang; Wu, Wanxia; Deng, Jie; Lan, Li; Shi, Sanjun

2017-08-01

An injectable, phospholipid-based phase transition gel (PPTG) has been developed for prolonging the release of ropivacaine (RO) for local anesthesia. PPTG was prepared by mixing phospholipids, medium-chain triglyceride and ethanol. Prior to injection, the PPTG is in a sol state with low viscosity. After subcutaneous injection, the PPTG rapidly forms a gel in situ, which acts as a drug release depot as verified by in vitro release profiles and in vivo pharmacokinetics. Administering RO-PPTG to rats led to a significantly smaller initial burst release than administering RO solution or RO base suspension. Nerve blockade in guinea pigs lasted 3-fold longer after injection of RO-PPTG than after injection of RO solution. RO-PPTG showed good biocompatibility and excellent degradability in vivo. These results suggest that this PPTG-based depot system may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity. The sustained release of local anesthetics at the surgical site after a single injection is the optimal method to control post-surgical pain. In situ forming implant is an attractive alternative for the sustained release of local anesthetics. However, its practical use is highly limited by certain drawbacks including high viscosity, involved toxic organic solvents and fast drug release. To date, phospholipids-based phase transition gel (PPTG) is emerging for clinical development because of the non-toxicity, biocompatibility and ready availability of phospholipids in body. Thus, we present a novel strategy for sustained release of local anesthetics to control post-surgical pain based on PPTG, which showed a prolonged duration of nerve blockade and excellent biocompatibility. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modified-release hydrocortisone to provide circadian cortisol profiles.

PubMed

Debono, Miguel; Ghobadi, Cyrus; Rostami-Hodjegan, Amin; Huatan, Hiep; Campbell, Michael J; Newell-Price, John; Darzy, Ken; Merke, Deborah P; Arlt, Wiebke; Ross, Richard J

2009-05-01

Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. The study was performed at a Clinical Research Facility. Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen. The key variables in the physiological cortisol profile included: peak 15.5 microg/dl (95% reference range 11.7-20.6), acrophase 0832 h (95% confidence interval 0759-0905), nadir less than 2 microg/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (sem) maximum observed concentration of 16.6 (1.4) microg/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels. By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol.

Anomalous fast dynamics of adsorbate overlayers near an incommensurate structural transition.

PubMed

Granato, Enzo; Ying, S C; Elder, K R; Ala-Nissila, T

2013-09-20

We investigate the dynamics of a compressively strained adsorbed layer on a periodic substrate via a simple two-dimensional model that admits striped and hexagonal incommensurate phases. We show that the mass transport is superfast near the striped-hexagonal phase boundary and in the hexagonal phase. For an initial step profile separating a bare substrate region (or "hole") from the rest of a striped incommensurate phase, the superfast domain wall dynamics leads to a bifurcation of the initial step profile into two interfaces or profiles propagating in opposite directions with a hexagonal phase in between. This yields a theoretical understanding of the recent experiments for the Pb/Si(111) system.

Mechanistic modelling of drug release from a polymer matrix using magnetic resonance microimaging.

PubMed

Kaunisto, Erik; Tajarobi, Farhad; Abrahmsen-Alami, Susanna; Larsson, Anette; Nilsson, Bernt; Axelsson, Anders

2013-03-12

In this paper a new model describing drug release from a polymer matrix tablet is presented. The utilization of the model is described as a two step process where, initially, polymer parameters are obtained from a previously published pure polymer dissolution model. The results are then combined with drug parameters obtained from literature data in the new model to predict solvent and drug concentration profiles and polymer and drug release profiles. The modelling approach was applied to the case of a HPMC matrix highly loaded with mannitol (model drug). The results showed that the drug release rate can be successfully predicted, using the suggested modelling approach. However, the model was not able to accurately predict the polymer release profile, possibly due to the sparse amount of usable pure polymer dissolution data. In addition to the case study, a sensitivity analysis of model parameters relevant to drug release was performed. The analysis revealed important information that can be useful in the drug formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Microencapsulation of rifampicin for the prevention of endophthalmitis: In vitro release studies and antibacterial assessment.

PubMed

Lee, Mi Yeon; Bourgeois, Sandrine; Almouazen, Eyad; Pelletier, Jocelyne; Renaud, François; Fessi, Hatem; Kodjikian, Laurent

2016-05-30

Rifampicin encapsulated microparticles were designed for intraocular injection after cataract surgery to prevent postoperative endophthalmitis. Microparticles were formulated by emulsification diffusion method using poly(lactic acid-co-glycolic acid) (PLGA) as polymer in order to propose a new form of rifampicin that overcome its limitations in intraocular delivery. Depending on processing formulation, different types of microparticles were prepared, characterized and evaluated by in vitro release studies. Two types of microparticles were selected to get a burst release of rifampicin, to reach minimal inhibitory concentrations to inhibit 90% of Staphylococcus epidermidis mainly involved in postoperative endophthalmitis, combined with a sustained release to maintain rifampicin concentration over 24h. The antibacterial activity and antiadhesive property on intraocular lenses were evaluated on S. epidermidis. Microparticles, with a rapid rifampicin release profile, showed an effect towards bacteria development similar to free rifampicin over 48h. However, slow-release profile microparticles exhibited a similar antibacterial effect during the first 24h, and were able to destroy all the S epidermidis in the medium after 30h. The association of the two formulations allowed obtaining interesting antibacterial profile. Moreover, rifampicin-loaded microparticles have shown a very efficient anti-adherent effect of S. epidermidis on intraocular lenses at 24h. These results propose rifampicin microparticles as suitable for antibioprophylaxis of the postoperative endophthalmitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Liquid Crystalline Systems Based on Glyceryl Monooleate and Penetration Enhancers for Skin Delivery of Celecoxib: Characterization, In Vitro Drug Release, and In Vivo Studies.

PubMed

Dante, Mariane de Cássia Lima; Borgheti-Cardoso, Livia Neves; Fantini, Marcia Carvalho de Abreu; Praça, Fabíola Silva Garcia; Medina, Wanessa Silva Garcia; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2018-03-01

Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB. Analysis of their phase behavior revealed the formation of cubic and hexagonal phases depending on the systems' composition. The systems' structure and composition markedly affected the in vitro CXB release profile. Oleic acid reduced CXB release rate, but association oleic acid/propylene glycol increased the drug release rate. The developed systems significantly reduced inflammation in an aerosil-induced rat paw edema model. The systems' composition and liquid crystalline structure influenced their anti-inflammatory potency. Cubic phase systems containing oleic acid/propylene glycol association reduced edema in a sustained manner, indicating that they modulate CXB release and permeation. Our findings demonstrate that the developed liquid crystalline systems are potential carriers for the skin delivery of CXB. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Energetics of a two-phase model of lithospheric damage, shear localization and plate-boundary formation

NASA Astrophysics Data System (ADS)

Bercovici, David; Ricard, Yanick

2003-03-01

The two-phase theory for compaction and damage proposed by Bercovici et al. (2001a, J. Geophys. Res.,106, 8887-8906) employs a nonequilibrium relation between interfacial surface energy, pressure and viscous deformation, thereby providing a model for damage (void generation and microcracking) and a continuum description of weakening, failure and shear localization. Here we examine further variations of the model which consider (1) how interfacial surface energy, when averaged over the mixture, appears to be partitioned between phases; (2) how variability in deformational-work partitioning greatly facilitates localization; and (3) how damage and localization are manifested in heat output and bulk energy exchange. Microphysical considerations of molecular bonding and activation energy suggest that the apparent partitioning of surface energy between phases goes as the viscosity of the phases. When such partitioning is used in the two-phase theory, it captures the melt-compaction theory of McKenzie (1984, J. Petrol.,25, 713-765) exactly, as well as the void-damage theory proposed in a companion paper (Ricard & Bercovici, submitted). Calculations of 1-D shear localization with this variation of the theory still show at least three possible regimes of damage and localization: at low stress is weak localization with diffuse slowly evolving shear bands; at higher stress strong localization with narrow rapidly growing bands exists; and at yet higher shear stress it is possible for the system to undergo broadly distributed damage and no localization. However, the intensity of localization is strongly controlled by the variability of the deformational-work partitioning with dilation rate, represented by the parameter γ. For γ>> 1, extreme localization is allowed, with sharp profiles in porosity (weak zones), nearly discontinuous separation velocities and effectively singular dilation rates. Finally, the bulk heat output is examined for the 1-D system to discern how much deformational work is effectively stored as surface energy. In the high-stress, distributed-damage cases, heat output is reduced as more interfacial surface energy is created. Yet, in either the weak or strong localizing cases, the system always releases surface energy, regardless of the presence of damage or not, and thus slightly more heat is in fact released than energy is input through external work. Moreover, increased levels of damage (represented by the maximum work-partitioning f*) make the localizing system release surface energy faster as damage enhances phase separation and focusing of the porosity field, thus yielding more rapid loss of net interfacial surface area. However, when cases with different levels of damage are compared at similar stages of development (say, the peak porosity of the localization) it is apparent that increased damage causes smaller relative heat release and retards loss of net interfacial surface energy. The energetics and energy partitioning of this damage and shear-localization model are applied to estimating the energy costs of forming plate boundaries and generating plates from mantle convection.

Volatile organic compounds released by blowfly larvae and pupae: new perspectives in forensic entomology.

PubMed

Frederickx, C; Dekeirsschieter, J; Brostaux, Y; Wathelet, J-P; Verheggen, F J; Haubruge, E

2012-06-10

To evaluate postmortem intervals (PMIs), one should take into account the determined age of necrophagous flies present on the cadaver. However, PMI determination needs further improvement, and rapid and accurate approaches have therefore to be developed. While previous studies have focussed on insect cuticular hydrocarbons, here we explore the volatile profile released by larvae and pupae of Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae). We monitored changes in volatile compounds daily, by headspace solid-phase microextraction, followed by gas chromatography-mass spectrometry. Branched and unbranched hydrocarbons, alcohols, esters and acids were identified, and the volatile profile was shown to vary, in both composition and quantity, with the age of the larva/pupa under investigation. We concluded, based on the analysis of the released volatile organic compounds, that it is possible to increase the accuracy of the estimated PMI, through improved estimation of the age of blowflies present on the cadaver. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles.

PubMed

Ebrahimi, Hossein Ali; Javadzadeh, Yousef; Hamidi, Mehrdad; Jalali, Mohammad Barzegar

2015-09-21

Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations. Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer. The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release. The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.

Releasing intracellular product to prepare whole cell biocatalyst for biosynthesis of Monascus pigments in water-edible oil two-phase system.

PubMed

Hu, Minglue; Zhang, Xuehong; Wang, Zhilong

2016-11-01

Selective releasing intracellular product in Triton X-100 micelle aqueous solution to prepare whole cell biocatalyst is a novel strategy for biosynthesis of Monascus pigments, in which cell suspension culture exhibits some advantages comparing with the corresponding growing cell submerged culture. In the present work, the nonionic surfactant Triton X-100 was successfully replaced by edible plant oils for releasing intracellular Monascus pigments. High concentration of Monascus pigments (with absorbance nearly 710 AU at 470 nm in the oil phase, normalized to the aqueous phase volume approximately 142 AU) was achieved by cell suspension culture in peanut oil-water two-phase system. Furthermore, the utilization of edible oil as extractant also fulfills the demand for application of Monascus pigments as natural food colorant.

Thermally coupled moving boundary model for charge-discharge of LiFePO4/C cells

NASA Astrophysics Data System (ADS)

Khandelwal, Ashish; Hariharan, Krishnan S.; Gambhire, Priya; Kolake, Subramanya Mayya; Yeo, Taejung; Doo, Seokgwang

2015-04-01

Optimal thermal management is a key requirement in commercial utilization of lithium ion battery comprising of phase change electrodes. In order to facilitate design of battery packs, thermal management systems and fast charging profiles, a thermally coupled electrochemical model that takes into account the phase change phenomenon is required. In the present work, an electrochemical thermal model is proposed which includes the biphasic nature of phase change electrodes, such as lithium iron phosphate (LFP), via a generalized moving boundary model. The contribution of phase change to the heat released during the cell operation is modeled using an equivalent enthalpy approach. The heat released due to phase transformation is analyzed in comparison with other sources of heat such as reversible, irreversible and ohmic. Detailed study of the thermal behavior of the individual cell components with changing ambient temperature, rate of operation and heat transfer coefficient is carried out. Analysis of heat generation in the various regimes is used to develop cell design and operating guidelines. Further, different charging protocols are analyzed and a model based methodology is suggested to design an efficient quick charging protocol.

LC-MS/MS Peptide Mapping with Automated Data Processing for Routine Profiling of N-Glycans in Immunoglobulins

NASA Astrophysics Data System (ADS)

Shah, Bhavana; Jiang, Xinzhao Grace; Chen, Louise; Zhang, Zhongqi

2014-06-01

Protein N-Glycan analysis is traditionally performed by high pH anion exchange chromatography (HPAEC), reversed phase liquid chromatography (RPLC), or hydrophilic interaction liquid chromatography (HILIC) on fluorescence-labeled glycans enzymatically released from the glycoprotein. These methods require time-consuming sample preparations and do not provide site-specific glycosylation information. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) peptide mapping is frequently used for protein structural characterization and, as a bonus, can potentially provide glycan profile on each individual glycosylation site. In this work, a recently developed glycopeptide fragmentation model was used for automated identification, based on their MS/MS, of N-glycopeptides from proteolytic digestion of monoclonal antibodies (mAbs). Experimental conditions were optimized to achieve accurate profiling of glycoforms. Glycan profiles obtained from LC-MS/MS peptide mapping were compared with those obtained from HPAEC, RPLC, and HILIC analyses of released glycans for several mAb molecules. Accuracy, reproducibility, and linearity of the LC-MS/MS peptide mapping method for glycan profiling were evaluated. The LC-MS/MS peptide mapping method with fully automated data analysis requires less sample preparation, provides site-specific information, and may serve as an alternative method for routine profiling of N-glycans on immunoglobulins as well as other glycoproteins with simple N-glycans.

Replacement of Ablators with Phase-Change Material for Thermal Protection of STS Elements

NASA Technical Reports Server (NTRS)

Kaul, Raj K.; Stuckey, Irvin; Munafo, Paul M. (Technical Monitor)

2002-01-01

As part of the research and development program to develop new Thermal Protection System (TPS) materials for aerospace applications at NASA's Marshall Space Flight Center (MSFC), an experimental study was conducted on a new concept for a non-ablative TPS material. Potential loss of TPS material and ablation by-products from the External Tank (ET) or Solid Rocket Booster (SRB) during Shuttle flight with the related Orbiter tile damage necessitates development of a non-ablative thermal protection system. The new Thermal Management Coating (TMC) consists of phase-change material encapsulated in micro spheres and a two-part resin system to adhere the coating to the structure material. The TMC uses a phase-change material to dissipate the heat produced during supersonic flight rather than an ablative material. This new material absorbs energy as it goes through a phase change during the heating portion of the flight profile and then the energy is slowly released as the phase-change material cools and returns to its solid state inside the micro spheres. The coating was subjected to different test conditions simulating design flight environments at the NASA/MSFC Improved Hot Gas Facility (IHGF) to study its performance.

Release profile of synthesized coumarin derivatives as a novel antibacterial agent from glass ionomer cement (GIC)

NASA Astrophysics Data System (ADS)

Rahman, Fatimah Suhaily Abdul; Osman, Hasnah; Mohamad, Dasmawati

2017-12-01

Glass ionomer cements (GIC) are widely used as dental restorative materials due to their aesthetics features and fluoride content. However, a capability of fluoride content in GIC to inhibit bacteria growth in an oral environment was insufficient for a long term which may lead to secondary caries. Therefore, two types of synthesized coumarin derivatives were incorporated with GIC to act as new antibacterial agent. However prior to the antibacterial evaluation, this study investigated the release profile of GIC incorporated with 3-Acetylcoumarin (GIC-1) and hydrazinyl thiosemicarbazide of coumarin derivatives (GIC-2) at three different concentrations of 0.5, 1.0 and 1.5 wt% up to 30 days. At early incubation period, GIC-1 revealed a higher release profile at 0.5 % fabrication that reached almost 45 % of cumulative release for 8 hours observational. Meanwhile, a slightly different output was obtained for GIC-2 in which 1.0 % fabrication of coumarin gave a better release in the initial hour. However, the pattern was replaced by 0.5 % substitution after 4 hours incubation time. A substitution of 1.5 % coumarin seems to be low in releasing activity for all materials. Conversely, in a longer period 1.0 % fabrication was discovered to be the highest coumarin release among others fabrications for both materials. Filler particle size and porosity of the materials were considered to be the main factor that may affect the coumarin release. Nonetheless, both synthesized coumarin derivatives can be incorporated with GIC as their release profile look very promising. Ultimately, the coumarin derivatives could improve the properties of GIC.

Bioavailability, safety, and pharmacodynamics of delayed-release dexlansoprazole administered as two 30 mg orally disintegrating tablets or one 60 mg capsule.

PubMed

Kukulka, Michael; Nudurupati, Sai; Perez, Maria Claudia

2016-11-01

Dual delayed-release dexlansoprazole is approved for use in adults as a 30 mg orally disintegrating tablet (ODT) or as 30 mg and 60 mg capsules. The pharmacokinetics, pharmacodynamics, and safety profile of two dexlansoprazole 30 mg ODTs were compared with one dexlansoprazole 60 mg capsule in this randomized, phase I, open-label, single-center, multiple-dose, two-period crossover study. Participants were randomized in one of two treatment sequences, each comprised two 5-day treatment periods during which two dexlansoprazole 30 mg ODTs or one 60 mg capsule was administered once daily. Pharmacokinetic parameters and the mean intragastric pH profile for the 24-hour period after dosing on days 1 and 5 were described. Adverse events were monitored during study duration and followed up with a phone call 5-10 days after the last dose of study drug. On day 1, peak observed plasma concentration ( C max ) values were similar between two 30 mg ODTs (1047 ng/ml) and one 60 mg capsule (1164 ng/ml). Systemic exposure, measured by the area under the plasma concentration-time curve (AUC), was approximately 25% lower after ODT administration. On day 5, mean pH after daily doses of two 30 mg ODT or one 60 mg capsule was 4.33 and 4.36, respectively; both regimens maintained intragastric pH above 4.0 for 60% of the 24-hour period. Headache was the most commonly reported adverse event (observed in 19.2% of participants); no adverse events leading to study withdrawal occurred. While systemic exposure (AUC) was 25% lower with ODT, peak concentrations ( C max ) after administration of two dexlansoprazole 30 mg ODTs and one 60 mg capsule were similar. The 24-hour intragastric pH control after administration of two dexlansoprazole 30 mg ODTs was equivalent to one dexlansoprazole 60 mg capsule. Both ODT and capsule were well tolerated.

Controlled delivery of basal insulin from phase-sensitive polymeric systems after subcutaneous administration: in vitro release, stability, biocompatibility, in vivo absorption, and bioactivity of insulin.

PubMed

Al-Tahami, Khaled; Oak, Mayura; Singh, Jagdish

2011-06-01

The purpose of this study was to investigate the phase-sensitive delivery systems (D,L-polylactide in triacetin) for controlled delivery of insulin at basal level. The effect of varying concentration of zinc, polymer, and insulin on the in vitro release of insulin was evaluated. Stability of released insulin was investigated by differential scanning calorimetry, circular dichroism, and matrix-assisted laser desorption/ionization time of flight mass spectrometry. In Vivo insulin absorption and bioactivity were studied in diabetic rats. In vitro and In Vivo biocompatibility of delivery systems were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and skin histology, respectively. Extended release profiles of insulin for 2, 4, and 8 weeks from delivery systems containing 20%, 30%, and 40% (w/v) polymer concentration was observed. A ratio of 1:5 insulin hexamer to zinc was shown to be optimum. Physical and chemical stability of released insulin was greatly conserved. In Vivo studies demonstrated controlled release of insulin with reduction in blood glucose for approximately 1 month. In vitro and In Vivo studies demonstrated that the delivery system was biocompatible and controlled the delivery of insulin for longer durations after single subcutaneous injection. Copyright © 2010 Wiley-Liss, Inc.

Alpha 2 LASSO Data Bundles

DOE Data Explorer

Gustafson, William Jr; Vogelmann, Andrew; Endo, Satoshi; Toto, Tami; Xiao, Heng; Li, Zhijin; Cheng, Xiaoping; Kim, Jinwon; Krishna, Bhargavi

2015-08-31

The Alpha 2 release is the second release from the LASSO Pilot Phase that builds upon the Alpha 1 release. Alpha 2 contains additional diagnostics in the data bundles and focuses on cases from spring-summer 2016. A data bundle is a unified package consisting of LASSO LES input and output, observations, evaluation diagnostics, and model skill scores. LES input include model configuration information and forcing data. LES output includes profile statistics and full domain fields of cloud and environmental variables. Model evaluation data consists of LES output and ARM observations co-registered on the same grid and sampling frequency. Model performance is quantified by skill scores and diagnostics in terms of cloud and environmental variables.

Effect of HPMC - E15 LV premium polymer on release profile and compression characteristics of chitosan/ pectin colon targeted mesalamine matrix tablets and in vitro study on effect of pH impact on the drug release profile.

PubMed

Newton, A M J; Lakshmanan, Prabakaran

2014-04-01

The study was designed to investigate the in vitro dissolution profile and compression characteristics of colon targeted matrix tablets prepared with HPMC E15 LV in combination with pectin and Chitosan. The matrix tablets were subjected to two dissolution models in various simulated fluids such as pH 1.2, 6, 6.8, 7.2, 5.5. The fluctuations in colonic pH conditions during IBD (inflammatory bowel disease) and the nature of less fluid content in the colon may limit the expected drug release in the polysaccharide-based matrices when used alone. The Hydrophilic hydroxyl propyl methylcellulose ether premium polymer (HPMC E15 LV) of low viscosity grade was used in the formulation design, which made an excellent modification in physical and compression characteristics of the granules. The release studies indicated that the prepared matrices could control the drug release until the dosage form reaches the colon and the addition HPMC E15 LV showed the desirable changes in the dissolution profile by its hydrophilic nature since the colon is known for its less fluid content. The hydrophilic HPMC E15 LV allowed the colonic fluids to enter into the matrix and confirmed the drug release at the target site from a poorly water soluble polymer such as Chitosan and also from water soluble Pectin. The dramatic changes occurred in the drug release profile and physicochemical characteristics of the Pectin, Chitosan matrix tablets when a premium polymer HPMC E15 LV added in the formulation design in the optimized concentration. Various drug release mechanisms used for the examination of drug release characteristics. Drug release followed the combined mechanism of diffusion, erosion, swelling and polymer entanglement. In recent decade, IBD attracts many patents in novel treatment methods by using novel drug delivery systems.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

PubMed Central

Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

2015-01-01

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

Diffractive Alvarez lens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barton, Ian M.; Dixit, Sham N.; Summers, Leslie J.

2000-01-01

A diffractive Alvarez lens is demonstrated that consists of two separate phase plates, each having complementary 16-level surface-relief profiles that contain cubic phase delays. Translation of these two components in the plane of the phase plates is shown to produce a variable astigmatic focus. Both spherical and cylindrical phase profiles are demonstrated with good accuracy, and the discrete surface-relief features are shown to cause less than {lambda}/10 wave-front aberration in the transmitted wave front over a 40 mmx80 mm region. (c) 2000 Optical Society of America.

Probing the kinetic energy-release dynamics of H-atom products from the gas-phase reaction of O(3P) with vinyl radical C2H3.

PubMed

Jang, Su-Chan; Choi, Jong-Ho

2014-11-21

The gas-phase radical-radical reaction dynamics of ground-state atomic oxygen O((3)P) with vinyl radicals C2H3 has been studied by combining the results of vacuum-ultraviolet laser-induced fluorescence spectroscopy in a crossed beam configuration with ab initio calculations. The two radical reactants O((3)P) and C2H3 were produced by photolysis of NO2 and supersonic flash pyrolysis of C2H3I, respectively. Doppler profile analysis of the kinetic energy release of the nascent H-atom products from the title reaction O((3)P) + C2H3→ H((2)S) + CH2CO (ketene) revealed that the average translational energy of the products and the average fraction of the total available energy were 7.03 ± 0.30 kcal mol(-1) and 7.2%. The empirical data combined with CBS-QB3 level ab initio theory and statistical calculations demonstrated that the title oxygen-hydrogen exchange reaction is a major reaction channel, through an addition-elimination mechanism involving the formation of a short-lived, dynamical complex on the doublet potential energy surface. On the basis of systematic comparison with several exchange reactions of hydrocarbon radicals, the observed kinetic energy release can be explained in terms of the weak impulse at the moment of decomposition in the loose transition state with a product-like geometry and a small reverse barrier along the exit channel.

Investigation of triacetin effect on indomethacin release from poly(methyl methacrylate) microspheres: evaluation of interactions using FT-IR and NMR spectroscopies.

PubMed

Yuksel, Nilufer; Baykara, Meltem; Shirinzade, Hanif; Suzen, Sibel

2011-02-14

The purpose of this study was to form indomethacin (IND)-loaded poly(methyl methacrylate) (PMMA) microspheres having an extended drug release profile over a period of 24h. Microspheres were prepared by solvent evaporation method using sucrose stearate as a droplet stabilizer. When PMMA was used alone for the preparation of microspheres, only 44% of IND could be released at the end of 8h. Triacetin was added to PMMA, as a minor phase, and the obtained microspheres showed a high yield process with recovery of 89.82% and incorporation efficiency of 102.3%. A desired release profile lasting 24h was achieved. Differential scanning calorimetry (DSC) analysis showed that IND was found to be in an amorphous state in the microspheres. Fourier transform infrared (FT-IR) and nuclear magnetic resonance ((1)H NMR) spectra suggested that there might be a hydrogen bond present between the IND hydroxyl group and PMMA. No interaction between triacetin and IND or PMMA as the formation of secondary bonds was observed. The release enhancement of IND from microspheres was attributed to the physical plasticization effect of triacetin on PMMA and, to some extent, the amorphous state of the drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.

PubMed

Lu, Cheng; Lu, Yi; Chen, Jian; Zhang, Wentong; Wu, Wei

2007-05-01

Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.

Fiber-optic projected-fringe digital interferometry

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1990-01-01

A phase-stepped projected-fringe interferometer was developed which uses a closed-loop fiber-optic phase-control system to make very accurate surface profile measurements. The closed-loop phase-control system greatly reduces phase-stepping error, which is frequently the dominant source of error in digital interferometers. Two beams emitted from a fiber-optic coupler are combined to form an interference fringe pattern on a diffusely reflecting object. Reflections off of the fibers' output faces are used to create a phase-indicating signal for the closed-loop optical phase controller. The controller steps the phase difference between the two beams by pi/2 radians in order to determine the object's surface profile using a solid-state camera and a computer. The system combines the ease of alignment and automated data reduction of phase-stepping projected-fringe interferometry with the greatly improved phase-stepping accuracy of our closed-loop phase-controller. The system is demonstrated by measuring the profile of a plate containing several convex surfaces whose heights range from 15 to 25 micron high.

Polychlorinated biphenyls in tree bark near a former manufacturing plant in Anniston, Alabama.

PubMed

Hermanson, Mark H; Johnson, Glenn W

2007-05-01

Tree bark samples were collected to identify the relative amounts and congener profiles of atmospheric polychlorinated biphenyls dissolved into bark lipids from the gas phase in Anniston, Alabama, USA, where PCBs were manufactured from the 1920s until 1971. The area is heavily contaminated with PCBs: At least 4550 metric tons (mt) of PCB and 14000 mt of PCB distillation residue, known as Montar, remain buried in two landfills near the plant site. A minimum of 20.5 mt of PCBs were emitted to the atmosphere by the plant between 1953 and 1971 based on emissions figures for 1970. Bark results show that total PCB concentrations range over more than three orders of magnitude from 171927 ng/g lipid near the plant/landfill area, dropping exponentially to 35 ng/g lipid at a distance of about 7 km. The exponential trend is highly correlated (r=-0.77) and significant (p<0.05). The most concentrated tree started growing after 1971 showing that atmospheric PCB concentrations remained high after PCB production ended. All PCB congener profiles show persistent congeners 31+28, 52, 66, 153, 138, and 180. Congener profiles from trees growing near the plant/landfill all have somewhat similar profiles but those growing during PCB production show high molecular mass compounds not usually found in the atmosphere and not found in younger trees, even in the most concentrated sample. We believe that high-temperature Montar disposal released high molecular mass PCBs into the gas phase which were dissolved into older tree bark lipids.

Mercury (Hg) in meteorites: Variations in abundance, thermal release profile, mass-dependent and mass-independent isotopic fractionation

NASA Astrophysics Data System (ADS)

Meier, Matthias M. M.; Cloquet, Christophe; Marty, Bernard

2016-06-01

We have measured the concentration, isotopic composition and thermal release profiles of Mercury (Hg) in a suite of meteorites, including both chondrites and achondrites. We find large variations in Hg concentration between different meteorites (ca. 10 ppb to 14,000 ppb), with the highest concentration orders of magnitude above the expected bulk solar system silicates value. From the presence of several different Hg carrier phases in thermal release profiles (150-650 °C), we argue that these variations are unlikely to be mainly due to terrestrial contamination. The Hg abundance of meteorites shows no correlation with petrographic type, or mass-dependent fractionation of Hg isotopes. Most carbonaceous chondrites show mass-independent enrichments in the odd-numbered isotopes 199Hg and 201Hg. We show that the enrichments are not nucleosynthetic, as we do not find corresponding nucleosynthetic deficits of 196Hg. Instead, they can partially be explained by Hg evaporation and redeposition during heating of asteroids from primordial radionuclides and late-stage impact heating. Non-carbonaceous chondrites, most achondrites and the Earth do not show these enrichments in vapor-phase Hg. All meteorites studied here have however isotopically light Hg (δ202Hg = ∼-7 to -1) relative to the Earth's average crustal values, which could suggest that the Earth has lost a significant fraction of its primordial Hg. However, the late accretion of carbonaceous chondritic material on the order of ∼2%, which has been suggested to account for the water, carbon, nitrogen and noble gas inventories of the Earth, can also contribute most or all of the Earth's current Hg budget. In this case, the isotopically heavy Hg of the Earth's crust would have to be the result of isotopic fractionation between surface and deep-Earth reservoirs.

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

Zn(2+) release behavior and surface characteristics of Zn/LDPE nanocomposites and ZnO/LDPE nanocomposites in simulated uterine solution.

PubMed

Yang, Zhihong; Xie, Changsheng; Xia, Xianping; Cai, Shuizhou

2008-11-01

To decrease the side effects of the existing copper-bearing intrauterine devices, the zinc/low-density polyethylene (Zn/LDPE) nanocomposite and zinc-oxide/low-density polyethylene (ZnO/LDPE) nanocomposite have been developed in our research for intrauterine devices (IUDs). In this study, the influences of preparation methods of nanocomposites and particle sizes of zinc and zinc oxide on Zn(2+) release from composites incubated in simulated uterine solution were investigated. All release profiles are biphasic: an initial rapid release phase is followed by a near zero-order release period. Zn(2+) release rates of nanocomposites prepared by compressing moulding are higher than those of the nanocomposites prepared by hot-melt extrusing. Compared with Zn(2+) release from the microcomposites, the release profiles of the nanocomposites exhibit a sharp decrease in Zn(2+) release rate in the first 18 days, an early onset of the zero-order release period and a high release rate of Zn(2+) at the later stage. The microstructure of the Zn/LDPE sample and the ZnO/LDPE sample after being incubated for 200 days was characterized by SEM, XRD and EDX techniques. The results show that the dissolution depth of ZnO/LDPE nanocomposite is about 60 mum. Lots of pores were formed on the surface of the Zn/LDPE sample and ZnO/LDPE sample, indicating that these pores can provide channels for the dissolution of nanoparticles in the matrix. The undesirable deposits that are composed of ZnO are only detected on the surface of Zn/LDPE nanocomposite, which may increase the risk of side effects associated with IUDs. It can be expected that ZnO/LDPE nanocomposite is more suitable for IUDs than Zn/LDPE nanocomposite.

Control of the U and Th behaviour in forest soils

NASA Astrophysics Data System (ADS)

Rihs, Sophie; Gontier, Adrien; Chabaux, François; Pelt, Eric; Turpault, Marie-Pierre

2015-04-01

U- and Th-series disequilibria and U, Th, Fe and Al speciation, were measured in several soil profiles from the experimental forest site of Breuil (Morvan, France) in order to address the impact of the vegetation on U and Th nuclides behaviour in soils. Thirty-five years after an experimental clear-felling of the native forest, the soil developed under two replacing mono-specific plantations (Oak and Douglas fir) were therefore compared to the undisturbed native forest soil. The analogous physical and chemical properties of these soils before the replacement were formerly demonstrated. Our results suggest that a shift in the Iron distribution seems to occur under the stand replaced by Oaks, with a significant replacement of Fe-bearing silicates by well crystallized Fe oxides. In contrast, such evolution was not demonstrated in the soils under Douglas fir. The concurrent loss of U and Th from the soils under Oak was tentatively related to the dissolution of Fe-bearing minerals. A mass balance calculation demonstrates that the observed increase in U oxalate-extracted fractions can quantitatively be explained through the entire profiles by a mere dissolution of up to 20% of U-Fe-bearing silicated minerals, without significant re-adsorption onto the amorphous Fe-Al oxides for U. Beside this primary release from Fe-bearing silicate minerals, the mobility of U and Th seems more likely controlled by Al phases rather than Fe oxides in surface layers during further pedogenic processes. Indeed, some of the U- and Th series disequilibria seem to be strongly related to Al dynamic in these layers. This relationship can be seen in the native forest profiles as well as in the replaced profiles, suggesting that this feature is not linked to the cover change. The redistribution of U and Th isotopes through these pedogenic processes therefore rule out the use of U-series for weathering rate determination in shallowest soils layers. In contrast, below 25 cm, the release of U and Th as well as the change of their distribution among the soil phases does not affect U- and Th series disequilibria. The activity ratios measured in oxalate leachates and the residues allow to demonstrate that the dissolution of a U-bearing silicate mineral and the consequent release of up to 20% of U would shift the (234U/238U) and (230Th/234U) ratios by less than 2%. These results therefore reveal that, after 35 years, no significant impact of the cover change on U-series disequilibria was recorded in the main part of the soil profiles, which, at this stage, justify the use of these nuclides as chronometers for weathering determination.

In Vivo Formation of Cubic Phase in Situ after Oral Administration of Cubic Phase Precursor Formulation Provides Long Duration Gastric Retention and Absorption for Poorly Water-Soluble Drugs.

PubMed

Pham, Anna C; Hong, Linda; Montagnat, Oliver; Nowell, Cameron J; Nguyen, Tri-Hung; Boyd, Ben J

2016-01-04

Lipid-based liquid crystalline systems based on the combination of digestible and nondigestible lipids have been proposed as potential sustained release delivery systems for oral delivery of poorly water-soluble drugs. The potential for cubic phase liquid crystal formation to induce dramatically extended gastric retention in vivo has been shown previously to strongly influence the resulting pharmacokinetics of incorporated drug. In vitro studies showing the in situ formation of cubic phase from a disordered precursor comprising a mixture of digestible and nondigestible lipids under enzymatic digestion have also recently been reported. Combining both concepts, here we show the potential for such systems to form in vivo, increasing gastric retention, and providing a sustained release effect for a model poorly water-soluble drug cinnarizine. A mixture of phytantriol and tributyrin at an 85:15 mass ratio, shown previously to form cubic phase under the influence of digestion, induced a similar pharmacokinetic profile to that in the absence of tributyrin, but completely different from tributyrin alone. The gastric retention of the formulation, assessed using micro-X-ray CT imaging, was also consistent with the pharmacokinetic behavior, where phytantriol alone and with 15% tributyrin was greater than that of tributyrin in the absence of phytantriol. Thus, the concept of precursor lipid systems that form cubic phase in situ during digestion in vivo has been demonstrated and opens new opportunities for sustained release of poorly water-soluble drugs.

The Investigation of Perchlorate/Iron Phase Mixtures as A Possible Source of Oxygen Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater, Mars

NASA Technical Reports Server (NTRS)

Sutter, B.; Heil, E.; Morris, R. V.; Archer, P. D.; Ming, D. W.; Niles, P. B.; Eigenbrode, J. L.; Franz, H.; Freissinet C.; Glavin, D. P.;

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

PubMed

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

Surfactant-assisted water exposed electrospinning of novel super hydrophilic polycaprolactone based fibers.

PubMed

Zargarian, S Sh; Haddadi-Asl, V

2017-08-01

Hybrid scaffolds prepared by blend electrospinning of Polycaprolactone and Pluronic solution benefit from enhanced fiber hydrophilicity and may offer satisfactory cell attachment and proliferation. To improve hybrid scaffold wettability and water swelling ratio, adequate amount of hydrophilic polymer is required; though this amount is limited by fiber surface enrichment of Pluronic and cannot be exceeded without affecting the scaffold mechanical properties. To overcome this problem, a routine blend electrospinning setup was modified by exposing the blend solution to water in order to attract Pluronic chains toward the surface of the charged jet. Morphology of scaffolds produced by the routine blend electrospinning and modified method was studied. A 50 nm thick Pluronic layer with linty appearance on the surface of the fibers fabricated by the modified method was detected. Drug-loaded fibers from modified method showed a moderate initial burst and then a prolonged release period while an abnormal two-stage phased release profile was observed for the routine blend method. The latter was associated to Pluronic/drug accumulations within the fibers fabricated by the routine method which resulted in fiber disintegration and a subsequent second burst release.

Carbamazepine parenteral nanoemulsions prepared by spontaneous emulsification process.

PubMed

Kelmann, Regina G; Kuminek, Gislaine; Teixeira, Helder F; Koester, Letícia S

2007-09-05

Carbamazepine (CBZ), a widely used anticonvulsant drug, is a poorly soluble drug with no parenteral treatment available for patients. This study was aimed at developing a nanoemulsion for CBZ intravenous delivery. The spontaneous emulsification method was used to prepare different formulations containing 2mg/mL CBZ. Likewise, a 2(2) full factorial experimental design was applied to study the influence of two independent variables (type of oil and type of lipophilic emulsifier) on emulsion physicochemical characteristics. The nanoemulsions were evaluated concerning droplet size, zeta potential, viscosity, drug content and association to oily phase. The formulation, which presented the best characteristics required for intravenous administration was selected and refined with respect to the lipophilic emulsifier content (increase from 5% to 6% of soy lecithin). This formulation was characterized and kept its properties in a satisfactory range over the evaluated period (3 months), i.e. droplet size around 150 nm, drug content around 95% and zeta potential around -40 mV. The transmission electron microscopy revealed emulsion droplets almost spherical in shape with an amorphous core, whereas the in vitro release profile assessed by dialysis bags demonstrated a release kinetics square root time dependent, with 95% of ca. having been released within 11h.

Winner of the society for biomaterials student award in the Ph.D. category for the annual meeting of the society for biomaterials, april 11-14, 2018, Atlanta, GA: Development of a bimodal, in situ crosslinking method to achieve multifactor release from electrospun gelatin.

PubMed

Kishan, Alysha; Walker, Taneidra; Sears, Nick; Wilems, Thomas; Cosgriff-Hernandez, Elizabeth

2018-05-01

To better mimic native tissue microenvironments, current efforts have moved beyond single growth factor delivery to more complex multiple growth factor delivery with distinct release profiles. Electrospun gelatin, a widely investigated drug delivery vehicle, requires postprocessing crosslinking techniques that generate a mesh with uniform crosslinking density, limiting the ability to deliver multiple factors at different rates. Herein, we describe a method to independently control release of multiple factors from a single electrospun gelatin mesh. Two in situ crosslinking modalities, photocrosslinking of methacyrlated gelatin and reactive crosslinking of gelatin with a diisocyanate, are coelectrospun to generate distinct fiber populations with different crosslinking chemistry and density in a single mesh. The photocrosslinked gelatin-methacrylate resulted in a relatively rapid release of a model protein (48 ± 12% at day 1, 96 ± 3% at day 10) due to diffusion of embedded protein from the crosslinked fibers. The reactive crosslinking system displayed a more sustained release (7 ± 5% at day 1, 33 ± 2% at day 10) that was attributed to the conjugation of protein to gelatin with the diisocyanate, requiring degradation of gelatin prior to diffusion out of the fibers. Both modalities displayed tunable release profiles. Subsequent release studies of a cospun mesh with two different crosslinked fiber populations confirmed that the cospun mesh displayed multifactor release with independent release profiles. Overall, this bimodal, in situ crosslinking approach enables the delivery of multiple factors with distinct release kinetics from a single mesh and is expected to have broad utility in tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1155-1164, 2018. © 2018 Wiley Periodicals, Inc.

Release of genetically engineered insects: a framework to identify potential ecological effects

PubMed Central

David, Aaron S; Kaser, Joe M; Morey, Amy C; Roth, Alexander M; Andow, David A

2013-01-01

Genetically engineered (GE) insects have the potential to radically change pest management worldwide. With recent approvals of GE insect releases, there is a need for a synthesized framework to evaluate their potential ecological and evolutionary effects. The effects may occur in two phases: a transitory phase when the focal population changes in density, and a steady state phase when it reaches a new, constant density. We review potential effects of a rapid change in insect density related to population outbreaks, biological control, invasive species, and other GE organisms to identify a comprehensive list of potential ecological and evolutionary effects of GE insect releases. We apply this framework to the Anopheles gambiae mosquito – a malaria vector being engineered to suppress the wild mosquito population – to identify effects that may occur during the transitory and steady state phases after release. Our methodology reveals many potential effects in each phase, perhaps most notably those dealing with immunity in the transitory phase, and with pathogen and vector evolution in the steady state phase. Importantly, this framework identifies knowledge gaps in mosquito ecology. Identifying effects in the transitory and steady state phases allows more rigorous identification of the potential ecological effects of GE insect release. PMID:24198955

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres.

PubMed

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f(1)), the similarity factor (f(2)), and the Rescigno index (ξ(1) and ξ(2)) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres

PubMed Central

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f1), the similarity factor (f2), and the Rescigno index (ξ1 and ξ2) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations. PMID:21674019

Lack of circadian regulation of melatonin rhythms in the sockeye salmon (Oncorhynchus nerka) in vivo and in vitro.

PubMed

Iigo, Masayuki; Azuma, Teruo; Iwata, Munehico

2007-01-01

Melatonin profiles were determined in the plasma in vivo and in the pineal organ in vitro of the sockeye salmon (Oncorhynchus nerka) under various light conditions to test whether they are under circadian regulation. When serial blood samples were taken at 4-h intervals for 3 days via a cannula inserted into the dorsal aorta, plasma melatonin exhibited significant fluctuation under a light-dark cycle, with higher levels during the dark phase than during the light phase. No rhythmic fluctuations persisted under either constant dark or constant light, with constant low and high levels, respectively. Melatonin release from the pineal organ in flow-through culture exhibited a similar pattern in response to the change in light conditions, with high and low release associated with the dark and light phases, respectively. These results indicate that melatonin production in the sockeye salmon is driven by light and darkness but lacks circadian regulation.

Impact of phase of the estrous cycle and season on LH surge profile and fertility in dairy cows treated with different GnRH analogs (gonadorelin vs. buserelin).

PubMed

Armengol-Gelonch, R; Mallo, J M; Ponté, D; Jimenez, A; Valenza, A; Souza, A H

2017-03-15

Our aim was to assess the GnRH-induced LH surge profile in dairy cows receiving two GnRH products (gonadorelin vs buserelin) given at proestrus or diestrus phase and to investigate whether season could alter LH surge profile in dairy cows. In Experiment 1, dairy cows at 108.2 ± 2.3 DIM, producing 41.5 ± 0.3 kg/day were randomized to receive, during proestrus and diestrus: Ovarelin ® i.m. (OVA; n = 56; 100 mg of gonadorelin diacetate tetrahydrate; Ceva Animal Health, France) or Receptal ® i.m. (REC; n = 52; 10 mcg of buserelin diacetate; MSD, Germany). In Experiment 1, blood samples were collected at hour 0 (just before GnRH treatment) at 30min, 1 h and then hourly until 5 h post-GnRH. In Experiment 2, cows were synchronized with a modified G-6-G protocol and randomized to receive either OVA or REC throughout the synchronization program. In Experiment 1, peak LH concentrations (ng/mL) were not affected by type of GnRH (OVA = 6.2 ± 0.4 vs REC = 6.7 ± 0.4; P = 0.37) or season (Cool = 6.8 ± 0.4 vs Warm = 6.1 ± 0.4; P = 0.22), and there were no interactions between GnRH type and phase of the estrous cycle or season. Interestingly, the area under the curve (AUC) of LH release (ng/ml*time) was significantly lower during warmer months (Cool = 20.3 ± 1.2 vs Warm = 16.9 ± 1.1; P = 0.04). As expected, LH peak was affected by phase of the cycle (proestrus = 8.2 ± 0.4 vs diestrus = 4.7 ± 0.4; P < 0.01). Ovarelin caused LH concentrations to increase faster, reaching highest concentration sooner (h) than REC (1.5 ± 0.1 vs 2.3 ± 0.1; P < 0.01). As a result, cows receiving OVA had greater circulating LH concentrations (ng/mL) at 1 h after GnRH treatment than cows receiving REC (P < 0.01). In contrast, cows treated with REC had longer (P = 0.01) intervals from peak until return to nadir. In Experiment 2, pregnancy per AI (P/AI) was similar for cows receiving either GnRH product during the synchronization protocol, with no detectable interactions between GnRH type and season. In conclusion, phase of the estrous cycle had a great impact on the GnRH-induced LH surge profile and cows during warm season had reduced AUC. Additionally, type of GnRH did not influence LH surge profile and P/AI in synchronized cows. Regardless of GnRH type, strategies to avoid heat stress and excessively high levels of circulating P4 near the time of GnRH treatment might help improve LH release profile in dairy cows, and ultimately increase P/AI. Copyright © 2017 Elsevier Inc. All rights reserved.

D-region differential-phase measurements and ionization variability studies

NASA Technical Reports Server (NTRS)

Weiland, R. M.; Bowhill, S. A.

1978-01-01

Measurements of electron densities in the D region are made by the partial-reflection differential-absorption and differential-phase techniques. The differential-phase data are obtained by a hard-wired phase-measuring system. Electron-sensity profiles obtained by the two techniques on six occasions are plotted and compared. Electron-density profiles obtained at the same time on 30 occasions during the years 1975 through 1977 are averaged to form a single profile for each technique. The effect of varying the assumed collision-frequency profile on these averaged profiles is studied. Time series of D-region electron-sensity data obtained by 3.4 minute intervals on six days during the summer of 1977 are examined for wave-like disturbances and tidal oscillations.

A modified commercial gas chromatograph for the continuous monitoring of the thermal degradation of sunflower oil and off-line solid phase extraction gas-chromatography-mass spectrometry characterization of released volatiles.

PubMed

Ontañon, I; Sanz, J; Escudero, A; de Marcos, S; Ferreira, V; Galbán, J

2015-04-03

A homemade flow cell attached to a commercial Gas Chromatograph equipped with a Flame Ionization Detector (FID) has been designed for the continuous monitoring of volatile compounds released during heating edible oils. Analytical parameters such as mass of sample, temperature and flow rates have been optimized and the obtained results have been compared with the corresponding thermographs from standard TG systems. Results show that under optimum conditions, the profiles of volatiles released upon heating are comparable to the profiles of TG curves, suggesting that the FID based system could be an alternative to TGA. Additionally, volatiles have been retained in a Lichrolut EN(®) resin, eluted and analyzed by Gas Chromatography-Mass Spectrometry. In this case, forty five compounds have been identified (acids, alcohols, alkanes, aldehydes, ketones and furans) and compared with the FID signals, working both in air or nitrogen atmosphere. It has been concluded that the oxidative thermal degradation is prevented in the presence of a nitrogen atmosphere. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced oral bioavailability of lurasidone by self-nanoemulsifying drug delivery system in fasted state.

PubMed

Miao, Yanfei; Sun, Jiqin; Chen, Guoguang; Lili, Ren; Ouyang, Pingkai

2016-08-01

The purpose of this work was to develop a new formulation to enhance the bioavailability and reduce the food effect of lurasidone using self-nanoemulsifying drug delivery systems (SNEDDSs). The formulation of lurasidone-SNEDDS was selected by the solubility and pseudo-ternary phase diagram studies. The prepared lurasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis, zeta potential and in vitro drug release. Lurasidone-SNEDDSs were administered to beagle dogs in fed and fasted state and their pharmacokinetics were compared to commercial available tablet as a control. The result showed lurasidone-SNEDDS was successfully prepared using Capmul MCM, Tween 80 and glycerol as oil phase, surfactant and co-surfactant, respectively. In vitro drug release studies indicated that the lurasidone-SNEDDS showed improved drug release profiles and the release behavior was not affected by the medium pH with total drug release of over 90% within 5 min. Pharmacokinetic study showed that the AUC(0-∞) and Cmax for lurasidone-SNEDDS are similar in the fasted and fed state, indicating essentially there is no food effect on the drug absorption. It was concluded that enhanced bioavailability and no food effect of lurasidone had been achieved by using SNEDDS.

Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

PubMed

Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

2017-12-01

We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

Comparison of Conventional and Microwave Assisted Heating on Carbohydrate Content, Antioxidant Capacity and Postprandial Glycemic Response in Oat Meals

PubMed Central

Olędzki, Remigiusz

2018-01-01

Minimally processed cereal breakfast products from whole grain entered the market due to consumer demand of more nutritional food with more controlled sugar release. However, the subsequent processing of such products with different cooking methods in the consumer’s kitchen may lead to significant differentiation of their nutritional value. Therefore, the evaluation of the impact of frequently used cooking methods on a final quality of breakfast cereals meal is needed. The present study investigates how the two different methods of heating, conventional and microwave (MW) assisted, affect the carbohydrate content, profile and resulting glycemic index of so prepared food as well as the antioxidant activity of meals. Two products available on the market—oat bran and flakes—were used. The highest starch content in fluid phase of oatmeal was detected in samples heated for 3 min with microwaves, regardless the type. The lowest starch content was obtained for 5 min MW heated flakes sample. The total content of glucose was about 1.5 times lower in bran vs. flakes oatmeal. The highest β-glucan content in fluid fraction was also observed for bran meal but its release was independent of applied conditions. PMID:29443904

Functional Peptidomics: Stimulus- and Time-of-Day-Specific Peptide Release in the Mammalian Circadian Clock.

PubMed

Atkins, Norman; Ren, Shifang; Hatcher, Nathan; Burgoon, Penny W; Mitchell, Jennifer W; Sweedler, Jonathan V; Gillette, Martha U

2018-06-20

Daily oscillations of brain and body states are under complex temporal modulation by environmental light and the hypothalamic suprachiasmatic nucleus (SCN), the master circadian clock. To better understand mediators of differential temporal modulation, we characterize neuropeptide releasate profiles by nonselective capture of secreted neuropeptides in an optic nerve horizontal SCN brain slice model. Releasates are collected following electrophysiological stimulation of the optic nerve/retinohypothalamic tract under conditions that alter the phase of the SCN activity state. Secreted neuropeptides are identified by intact mass via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found time-of-day-specific suites of peptides released downstream of optic nerve stimulation. Peptide release was modified differentially with respect to time-of-day by stimulus parameters and by inhibitors of glutamatergic or PACAPergic neurotransmission. The results suggest that SCN physiology is modulated by differential peptide release of both known and unexpected peptides that communicate time-of-day-specific photic signals via previously unreported neuropeptide signatures.

Combining strategies to optimize a gel formulation containing miconazole: the influence of modified cyclodextrin on textural properties and drug release.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Freire, Cristina; Santos, Delfim; Veiga, Francisco

2010-06-01

Miconazol, an antimycotic drug, is commonly formulated into semisolid formulations designed to be applied in the oral cavity to treat oral candidiasis. However, given its limited aqueous solubility, permeation through the biological membranes is low and therefore its activity is also limited. Cyclodextrins (CDs) have been widely used to increase the solubility and stability of poorly water-soluble drugs. The aim of this study is to formulate a gel containing an inclusion complex between a modified CD, methyl-beta-cyclodextrin (MbetaCD), and miconazole (MCZ). The influence of the CD on the textural properties of the prepared gel and the drug release from formulation were evaluated. The gels were prepared using two polymers, Carbopol 71G and Pluronic F127, which were selected taking into account their bioadhesiveness and thermal-sensitive gelling properties, respectively. Texture profile analyses were performed at two different temperatures to ascertain the influence of the temperature on the gel texture properties. The in vitro MCZ release profiles from the prepared gel and the commercial gel formulations were evaluated and compared using modified Franz diffusion cells. The addition of MbetaCD to the gel resulted in a decrease of the gel adhesiveness and firmness, and the MCZ release profile through f1 and f2 proved to be similar to the commercial product. A gel comprising miconazol in the form of an inclusion complex with MbetaCD showed suitable textural properties to be applied to the buccal mucosa. The MbetaCD enhanced the solubility of the MCZ in the gel formulation resulting in adequate in vitro drug release profiles.

Mars entry guidance based on an adaptive reference drag profile

NASA Astrophysics Data System (ADS)

Liang, Zixuan; Duan, Guangfei; Ren, Zhang

2017-08-01

The conventional Mars entry tracks a fixed reference drag profile (FRDP). To improve the landing precision, a novel guidance approach that utilizes an adaptive reference drag profile (ARDP) is presented. The entry flight is divided into two phases. For each phase, a family of drag profiles corresponding to various trajectory lengths is planned. Two update windows are investigated for the reference drag profile. At each window, the ARDP is selected online from the profile database according to the actual range-to-go. The tracking law for the selected drag profile is designed based on the feedback linearization. Guidance approaches using the ARDP and the FRDP are then tested and compared. Simulation results demonstrate that the proposed ARDP approach achieves much higher guidance precision than the conventional FRDP approach.

Deep-release of Epon 828 epoxy from the shock-driven reaction product phase

NASA Astrophysics Data System (ADS)

Lang, John; Fredenburg, Anthony; Coe, Joshua; Dattelbaum, Dana

2017-06-01

A challenge in improving equations-of-state (EOS) for polymers and their product phase is the lack of off-Hugoniot data. Here, we describe a novel experimental approach for obtaining release pathways along isentropes from the shocked products. A series of gas-gun experiments was conducted to obtain release isentropes of the products for 70/30 wt% Epon 828 epoxy resin/Jeffamine T-403 curing agent. Thin epoxy flyers backed by a low-density syntactic foam were impacted into LiF windows at up to 6.3 mm/ μs, creating stresses in excess of those required for reaction ( 25 GPa). Following a sustained shock input, a rarefaction fan from the back of the thin flyer reduced the pressure in the epoxy products along a release isentrope. Optical velocimetry (PDV) was used to measure the particle velocity at the epoxy/LiF interface. Numerical simulations using several different EOS describing the reactant-to-product transformation were conducted, and the results were compared with measured wave profiles. The best agreement with experiment was obtained using separate tabular EOS for the polymer ``reactant'' (e.g. epoxy) and product mixture, suggesting the transition to the products is irreversible.

Atmospheric PM and volatile organic compounds released from Mediterranean shrubland wildfires

NASA Astrophysics Data System (ADS)

Garcia-Hurtado, Elisa; Pey, Jorge; Borrás, Esther; Sánchez, Pilar; Vera, Teresa; Carratalá, Adoración; Alastuey, Andrés; Querol, Xavier; Vallejo, V. Ramon

2014-06-01

Wildfires produce a significant release of gases and particles affecting climate and air quality. In the Mediterranean region, shrublands significantly contribute to burned areas and may show specific emission profiles. Our objective was to depict and quantify the primary-derived aerosols and precursors of secondary particulate species released during shrubland experimental fires, in which fire-line intensity values were equivalent to those of moderate shrubland wildfires, by using a number of different methodologies for the characterization of organic and inorganic compounds in both gas-phase and particulate-phase. Emissions of PM mass, particle number concentrations and organic and inorganic PMx components during flaming and smouldering phases were characterized in a field shrubland fire experiment. Our results revealed a clear prevalence of K+ and SO42- as inorganic ions released during the flaming-smouldering processes, accounting for 68-80% of the inorganic soluble fraction. During the residual-smouldering phases, in addition to K+ and SO42-, Ca2+ was found in significant amounts probably due the predominance of re-suspension processes (ashes and soil dust) over other emission sources during this stage. Concerning organic markers, the chromatograms were dominated by phenols, n-alkanals and n-alkanones, as well as by alcohol biomarkers in all the PMx fractions investigated. Levoglucosan was the most abundant degradation compound with maximum emission factors between 182 and 261 mg kg-1 in PM2.5 and PM10 respectively. However, levoglucosan was also observed in significant amounts in the gas-phase. The most representative organic volatile constituents in the smoke samples were alcohols, carbonyls, acids, monocyclic and bicyclic arenes, isoprenoids and alkanes compounds. The emission factors obtained in this study may contribute to the validation and improvement of national and international emission inventories of this intricate and diffuse emission source.

Development of theophylline sustained release dosage form based on Kollidon SR.

PubMed

Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

2002-01-01

Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

Release Kinetics of Paclitaxel and Cisplatin from Two and Three Layered Gold Nanoparticles

PubMed Central

England, Christopher G.; Miller, M. Clarke; Kuttan, Ashani; Trent, John O.; Frieboes, Hermann B.

2015-01-01

Gold nanoparticles functionalized with biologically-compatible layers may achieve stable drug release while avoiding adverse effects in cancer treatment. We study cisplatin and paclitaxel release from gold cores functionalized with hexadecanethiol (TL) and phosphatidylcholine (PC) to form two-layer nanoparticles, or TL, PC, and high density lipoprotein (HDL) to form three-layer nanoparticles. Drug release was monitored for 14 days to assess long term effects of the core surface modifications on release kinetics. Release profiles were fitted to previously developed kinetic models to differentiate possible release mechanisms. The hydrophilic drug (cisplatin) showed an initial (5-hr.) burst, followed by a steady release over 14 days. The hydrophobic drug (paclitaxel) showed a steady release over the same time period. Two layer nanoparticles released 64.0 ± 2.5% of cisplatin and 22.3 ± 1.5% of paclitaxel, while three layer nanoparticles released the entire encapsulated drug. The Korsmeyer-Peppas model best described each release scenario, while the simplified Higuchi model also adequately described paclitaxel release from the two layer formulation. We conclude that functionalization of gold nanoparticles with a combination of TL and PC may help to modulate both hydrophilic and hydrophobic drug release kinetics, while the addition of HDL may enhance long term release of hydrophobic drug. PMID:25753197

Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

PubMed

Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

2017-05-01

In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of drug release and matrix degradation of electrospun poly(DL-lactide) fibers with paracetanol inoculation.

PubMed

Cui, Wenguo; Li, Xiaohong; Zhu, Xinli; Yu, Guo; Zhou, Shaobing; Weng, Jie

2006-05-01

This study was aimed at assessing the potential use of electrospun fibers as drug delivery vehicles with focus on the different diameters and drug contents to control drug release and polymer fiber degradation. A drug-loaded solvent-casting polymer film was made with an average thickness of 100 microm for comparative purposes. DSC analysis indicated that electrospun fibers had a lower T(g) but higher transition enthalpy than solvent-casting polymer film due to the inner stress and high degree of alignment and orientation of polymer chains caused by the electrospinning process. Inoculation of paracetanol led to a further slight decrease in the T(g) and transition enthalpy. An in vitro drug release study showed that a pronounced burst release or steady release phase was initially observed followed by a plateau or gradual release during the rest time. Fibers with a larger diameter exhibited a longer period of nearly zero order release, and higher drug encapsulation led to a more significant burst release after incubation. In vitro degradation showed that the smaller diameter and higher drug entrapment led to more significant changes of morphologies. The electrospun fiber mat showed almost no molecular weight reduction, but mass loss was observed for fibers with small and medium size, which was characterized with surface erosion and inconsistent with the ordinarily polymer degrading form. Further wetting behavior analysis showed that the high water repellent property of electrospun fibers led to much slower water penetration into the fiber mat, which may contribute to the degradation profiles of surface erosion. The specific degradation profile and adjustable drug release behaviors by variation of fiber characteristics made the electrospun nonwoven mat a potential drug delivery system rather than polymer films and particles.

MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cifter, G; Ngwa, W; Univ Massachusetts Lowell, Lowell, MA

2015-06-15

Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescentmore » GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT.« less

In vivo release of levonorgestrel from Sino-implant (II) — an innovative comparison of explant data.

PubMed

Callahan, Rebecca L; Taylor, Douglas; Jenkins, David W; Owen, Derek H; Cheng, Linan; Cancel, Aida M; Dorflinger, Laneta J; Steiner, Markus J

2015-10-01

Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants. LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions.

PubMed

Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana

2005-05-30

The purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric glycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudo-ternary phase diagram at surfactant-cosurfactant mass ratio (K(m) 1:1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 microgcm(-2)h(-1) (W/O microemulsion) to 117.94 microgcm(-2)h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29.38-63.70 microgcm(-2)h(-1)) suggested that bicontinuous microstructure hampers the release of the amphiphilic drug.

Next generation radiotherapy biomaterials loaded with high-Z nanoparticles

NASA Astrophysics Data System (ADS)

Cifter, Gizem

This research investigates the dosimetric feasibility of using high-Z nanoparticles as localized radiosensitizers to boost the dose to the residual tumor cells during accelerated partial breast irradiation while minimizing the dose to surrounding healthy tissue. Analytical microdosimetry calculations were carried out to calculate dose enhancement (DEF) in the presence of high-Z nanoparticles. It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. Prototype smart biomaterials were produced by incorporating the GNPs in poly (D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. In vitro release of GNPs was monitored over time by optical/spectroscopy methods as a function of various design parameters. The prototype smart biomaterials displayed sustained customizable release of NPs in-vitro, reaching a burst release profile approximately after 25 days. The results also show that customizable release profiles can be achievable by varying GNP concentrations that are embedded within smart biomaterials, as well as other design parameters. This would potentially allow customizable local dose boost resulting in diverse treatment planning opportunities for individual cases. Considered together, the results provide preliminary data for development of next generation of RT biomaterials, which can be employed at no additional inconvenience to RT patients.

Berry phase in controlled light propagation and storage

NASA Astrophysics Data System (ADS)

Raczyński, Andrzej; Zaremba, Jarosław; Zielińska-Raczyńska, Sylwia

2018-04-01

It is shown that during light storage in an atomic medium in the Λ configuration, with not only the amplitude of the control field but also its phase changing adiabatically, a photon gains a Berry (geometric) phase. In the case of the tripod configuration with two probe fields the Berry phase is replaced by a 2 ×2 matrix. The probe fields are shown to be superpositions of two modes, each of them being characterized not only by its own velocity but also by its own Berry phase. If after light storage photons are released backwards, the contributions of the two modes interfere and the distribution of the outgoing photons can be steered by changing the difference between the Berry phases of the modes, due to the choice of the control field at the storage and release stages. In particular, one can turn a single photon of one of the probe fields into a photon of the other field or essentially modify coherent states of the incoming pulses.

Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

PubMed

Tan, Q Y; Xu, M L; Wu, J Y; Yin, H F; Zhang, J Q

2012-04-01

A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

Development and application of a robust N-glycan profiling method for heightened characterization of monoclonal antibodies and related glycoproteins.

PubMed

Shang, Tanya Q; Saati, Andrew; Toler, Kelly N; Mo, Jianming; Li, Heyi; Matlosz, Tonya; Lin, Xi; Schenk, Jennifer; Ng, Chee-Keng; Duffy, Toni; Porter, Thomas J; Rouse, Jason C

2014-07-01

A highly robust hydrophilic interaction liquid chromatography (HILIC) method that involves both fluorescence and mass spectrometric detection was developed for profiling and characterizing enzymatically released and 2-aminobenzamide (2-AB)-derivatized mAb N-glycans. Online HILIC/mass spectrometry (MS) with a quadrupole time-of-flight mass spectrometer provides accurate mass identifications of the separated, 2-AB-labeled N-glycans. The method features a high-resolution, low-shedding HILIC column with acetonitrile and water-based mobile phases containing trifluoroacetic acid (TFA) as a modifier. This column and solvent system ensures the combination of robust chromatographic performance and full compatibility and sensitivity with online MS in addition to the baseline separation of all typical mAb N-glycans. The use of TFA provided distinct advantages over conventional ammonium formate as a mobile phase additive, such as, optimal elution order for sialylated N-glycans, reproducible chromatographic profiles, and matching total ion current chromatograms, as well as minimal signal splitting, analyte adduction, and fragmentation during HILIC/MS, maximizing sensitivity for trace-level species. The robustness and selectivity of HILIC for N-glycan analyses allowed for method qualification. The method is suitable for bioprocess development activities, heightened characterization, and clinical drug substance release. Application of this HILIC/MS method to the detailed characterization of a marketed therapeutic mAb, Rituxan(®), is described. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Kinetics for the distribution of acrylamide in French fries, fried oil and vapour during frying of potatoes.

PubMed

Hsu, Hui-Tsung; Chen, Ming-Jen; Tseng, Tzu-Ping; Cheng, Li-Hsin; Huang, Li-Jen; Yeh, Tai-Sheng

2016-11-15

Kinetic analysis for the formation of acrylamide in heated foods has been typically performed using only measured data of acrylamide in foods; however, its possible loss caused by release from heated foods into fried oil and air has seldom been considered. The results obtained from the monitoring of acrylamide by frying French fries indicated that acrylamide is distributed in three phases: French fries, frying oil, and air. From the evolved gas analysis of acrylamide and the measured concentration profile of the total acrylamide amount present in these phases, the kinetic behaviour for acrylamide formation does not obey the commonly used model of two-step consecutive reactions during frying, while a lumped kinetic model was proposed for the total acrylamide amount. Moreover, a high acrylamide level in air was observed, implying that, apart from consumers of French fries, fast-food restaurant workers are potentially subject to occupational hazards from acrylamide inhalation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Direct comparison of two different mesalamine formulations for the maintenance of remission in patients with ulcerative colitis: a double-blind, randomized study.

PubMed

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Aida, Yoshiyuki; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-09-01

Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC. In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools. In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations. The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289).

The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

PubMed

Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

2017-08-01

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

PubMed Central

Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

2014-01-01

Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

PubMed

Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

2013-01-01

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

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

PubMed

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

2012-04-01

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

Temperature-Induced Protein Release from Water-in-Oil-in-Water Double Emulsions

PubMed Central

Rojas, Edith C.; Staton, Jennifer A.; John, Vijay T.; Papadopoulos, Kyriakos D.

2009-01-01

A model water-in-oil-in-water (W1/O/W2) double emulsion was prepared by a two-step emulsification procedure and subsequently subjected to temperature changes that caused the oil phase to freeze and thaw while the two aqueous phases remained liquid. Our previous work on individual double-emulsion globules1 demonstrated that crystallizing the oil phase (O) preserves stability, while subsequent thawing triggers coalescence of the droplets of the internal aqueous phase (W1) with the external aqueous phase (W2), termed external coalescence. Activation of this instability mechanism led to instant release of fluorescently tagged bovine serum albumin (fluorescein isothiocyanate (FITC)-BSA) from the W1 droplets and into W2. These results motivated us to apply the proposed temperature-induced globule-breakage mechanism to bulk double emulsions. As expected, no phase separation of the emulsion occurred if stored at temperatures below 18 °C (freezing point of the model oil n-hexadecane), whereas oil thawing readily caused instability. Crucial variables were identified during experimentation, and found to greatly influence the behavior of bulk double emulsions following freeze-thaw cycling. Adjustment of these variables accounted for a more efficient release of the encapsulated protein. PMID:18543998

Mobility of arsenic in a Bangladesh aquifer: Inferences from geochemical profiles, leaching data, and mineralogical characterization

NASA Astrophysics Data System (ADS)

Swartz, Christopher H.; Blute, Nicole Keon; Badruzzman, Borhan; Ali, Ashraf; Brabander, Daniel; Jay, Jenny; Besancon, James; Islam, Shafiqul; Hemond, Harold F.; Harvey, Charles F.

2004-11-01

Aquifer geochemistry was characterized at a field site in the Munshiganj district of Bangladesh where the groundwater is severely contaminated by As. Vertical profiles of aqueous and solid phase parameters were measured in a sandy deep aquifer (depth >150 m) below a thick confining clay (119 to 150 m), a sandy upper aquifer (3.5 to 119 m) above this confining layer, and a surficial clay layer (<3.5 m). In the deep aquifer and near the top of the upper aquifer, aqueous As levels are low (<10 μg/L), but aqueous As approaches a maximum of 640 μg/L at a depth of 30 to 40 m and falls to 58 μg/L near the base (107 m) of the upper aquifer. In contrast, solid phase As concentrations are uniformly low, rarely exceeding 2 μg/g in the two sandy aquifers and never exceeding 10 μg/g in the clay layers. Solid phase As is also similarly distributed among a variety of reservoirs in the deep and upper aquifer, including adsorbed As, As coprecipitated in solids leachable by mild acids and reductants, and As incorporated in silicates and other more recalcitrant phases. One notable difference among depths is that sorbed As loads, considered with respect to solid phase Fe extractable with 1 N HCl, 0.2 M oxalic acid, and a 0.5 M Ti(III)-citrate-EDTA solution, appear to be at capacity at depths where aqueous As is highest; this suggests that sorption limitations may, in part, explain the aqueous As depth profile at this site. Competition for sorption sites by silicate, phosphate, and carbonate oxyanions appear to sustain elevated aqueous As levels in the upper aquifer. Furthermore, geochemical profiles are consistent with the hypothesis that past or ongoing reductive dissolution of Fe(III) oxyhydroxides acts synergistically with competitive sorption to maintain elevated dissolved As levels in the upper aquifer. Microprobe data indicate substantial spatial comapping between As and Fe in both the upper and deep aquifer sediments, and microscopic observations reveal ubiquitous Fe coatings on most solid phases, including quartz, feldspars, and aluminosilicates. Extraction results and XRD analysis of density/magnetic separates suggest that these coatings may comprise predominantly Fe(II) and mixed valence Fe solids, although the presence of Fe(III) oxyhydroxides can not be ruled out. These data suggest As release may continue to be linked to dissolution processes targeting Fe, or Fe-rich, phases in these aquifers.

Ionic liquid phases with comprehensive two-dimensional gas chromatography of fatty acid methyl esters.

PubMed

Pojjanapornpun, Siriluck; Nolvachai, Yada; Aryusuk, Kornkanok; Kulsing, Chadin; Krisnangkura, Kanit; Marriott, Philip J

2018-02-17

New generation inert ionic liquid (iIL) GC columns IL60i, IL76i and IL111i, comprising phosphonium or imidazolium cationic species, were investigated for separation of fatty acid methyl esters (FAME). In general, the iIL phases provide comparable retention times to their corresponding conventional columns, with only minor selectivity differences. The average tailing factors and peak widths were noticeably improved (reduced) for IL60i and IL76i, while they were slightly improved for IL111i. Inert IL phase columns were coupled with conventional IL columns in comprehensive two-dimensional GC (GC × GC) with a solid-state modulator which offers variable modulation temperature (T M ), programmable T M during analysis and trapping stationary phase material during the trap/release (modulation) process, independent of oven T and column sets. Although IL phases are classified as polar, relative polarity of the two phases comprising individual GC × GC column sets permits combination of less-polar IL/polar IL and polar IL/less-polar IL column sets; it was observed that a polar/less-polar column set provided better separation of FAME. A higher first dimension ( 1 D) phase polarity combined with a lower 2 D phase polarity, for instance 1 D IL111i with 2 D IL59 gave the best result; the greater difference in 1 D/ 2 D phase polarity results in increasing occupancy of peak area in the 2D space. The IL111i/IL59 column set was selected for analysis of fatty acids in fat and oil products (butter, margarine, fish oil and canola oil). Compared with the conventional IL111, IL111i showed reduced column bleed which makes this more suited to GC × GC analysis of FAME. The proposed method offers a fast profiling approach with good repeatability of analysis of FAME.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

Design of sustained release tablet containing fucoidan.

PubMed

Tran, Thao Truong-Dinh; Ngo, Dai Kieu-Phuong; Vo, Toi Van; Tran, Phuong Ha-Lien

2015-01-01

The study introduced a new therapeutic agent, fucoidan, which can offer potential medical treatments including anti-inflammatory and anti-coagulant activities, as well as anti-proliferative effects on cancer cells. Fucoidan was included in sustained release formulations expected for an effective plasma drug concentration for approximately 24 h. The matrices based on the two polymers hydroxypropyl methycellulose (HPMC) and polyethylene oxide (PEO) were prepared with various ratios between the polymers and fucoidan. The dissolution profiles of various matrix tablets performed in enzyme-free simulated intestinal fluid (pH 6.8) for 24 h indicated a higher potential of PEO-based matrix tablets in sustaining release of fucoidan. The swelling and erosion of the tablets were also characterized to elucidate the difference among those dissolution profiles.

A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer's disease: two phase I studies in healthy volunteers.

PubMed

Boinpally, Ramesh; Chen, Laishun; Zukin, Stephen R; McClure, Natalie; Hofbauer, Robert K; Periclou, Antonia

2015-07-01

Combining two standard-of-care medications for Alzheimer's disease (AD) into a single once-daily dosage unit may improve treatment adherence, facilitate drug administration, and reduce caregiver burden. A new fixed-dose combination (FDC) capsule containing 28 mg memantine extended release (ER) and 10 mg donepezil was evaluated for bioequivalence with co-administered commercially available memantine ER and donepezil, and for bioavailability with regard to food intake. Two phase I, single-dose, randomized, open-label, crossover studies were conducted in 18- to 45-year-old healthy individuals. In MDX-PK-104 study, fasting participants (N = 38) received co-administered memantine ER and donepezil or the FDC. In MDX-PK-105 study, participants (N = 36) received three treatments: intact FDC taken while fasting or after a high-fat meal, or FDC contents sprinkled on applesauce while fasting. Standard pharmacokinetic parameters for memantine and donepezil were calculated from the plasma concentration time-curve using non-compartmental analyses. Linear mixed-effects models were used to compare: (a) FDC versus co-administered individual drugs; (b) FDC fasted versus with food; and (c) FDC sprinkled on applesauce versus FDC intact, both fasted. Safety parameters were also evaluated. The FDC capsule was bioequivalent to co-administered memantine ER and donepezil. There was no significant food effect on the bioavailability of the FDC components. There were no clinically relevant differences in time to maximum plasma concentration or safety profiles across treatments. An FDC capsule containing 28 mg memantine ER and 10 mg donepezil is bioequivalent to commercially available memantine ER and donepezil, and bioavailability is not affected by food intake or sprinkling of capsule contents on applesauce.

Pharmacokinetic profile of extended-release versus immediate-release oral naproxen sodium after single and multiple dosing under fed and fasting conditions: two randomized, open-label trials.

PubMed

Laurora, Irene; Wang, Yuan

2016-10-01

Extended-release (ER) naproxen sodium provides pain relief for up to 24 hours with a single dose (660 mg/day). Its pharmacokinetic profile after single and multiple dosing was compared to immediate release (IR) naproxen sodium in two randomized, open-label, crossover studies, under fasting and fed conditions. Eligible healthy subjects were randomized to ER naproxen sodium 660-mg tablet once daily or IR naproxen sodium 220-mg tablet twice daily (440 mg initially, followed by 220 mg 12 hours later). Primary variables: pharmacokinetic parameters after singleday administration (day 1) and at steady state after multiple-day administration (day 6). Total exposure was comparable for both treatments under fasting and fed conditions. After fasting: peak naproxen concentrations were slightly lower with ER naproxen sodium than with IR naproxen sodium but were reached at a similar time. Fed conditions: mean peak concentrations were comparable but reached after a longer time with ER vs. IR naproxen sodium. ER naproxen sodium was well tolerated, with a similar safety profile to IR naproxen sodium. The total exposure of ER naproxen sodium (660 mg) is comparable to IR naproxen sodium (220 mg) when administered at the maximum over the counter (OTC) dose of 660-mg daily dose on a single day and over multiple days. The rate of absorption is delayed under fed conditions.

The National LUST Cleanup Backlog: A Study of Opportunities

EPA Pesticide Factsheets

To understand the makeup of UST releases remaining and why the pace of cleanups is slowing, EPA undertook a two-phase, data-driven analysis of the cleanups remaining as of 2006 (Phase 1) and 2009 (Phase 2).

Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies.

PubMed

Froelich, Anna; Osmałek, Tomasz; Snela, Agnieszka; Kunstman, Paweł; Jadach, Barbara; Olejniczak, Marta; Roszak, Grzegorz; Białas, Wojciech

2017-12-01

Microemulsion-based semisolid systems may be considered as an interesting alternative to the traditional dosage forms applied in topical drug delivery. Mechanical properties of topical products are important both in terms of application and dosage form effectiveness. In this study we designed and evaluated novel microemulsion-based gels with indomethacin and analyzed the factors affecting their mechanical characteristics and drug release. The impact of the microemulsion composition on the extent of isotropic region was investigated with the use of pseudoternary phase diagrams. Selected microemulsions were analyzed in terms of electrical conductivity and surface tension in order to determine the microemulsion type. Microemulsions were transformed into polymer-based gels and subjected to rheological and textural studies. Finally, the indomethacin release from the analyzed gels was studied and compared to commercially available product. The extent of isotropic domain in pseudoternary phase diagrams seems to be dependent on the polarity of the oil phase. The surface tension and conductivity monitored as a function of water content in microemulsion systems revealed possible structural transformations from w/o through bicontinuous systems into o/w. The mechanical properties of semisolid microemulsion-based systems depended on the composition of surface active agents and the drug presence. The drug release profiles observed in the case of the investigated gels differed from those recorded for the commercially available product which was most probably caused by the different structure of both systems. Copyright © 2017 Elsevier Inc. All rights reserved.

An Injectable System for Local and Sustained Release of Antimicrobial Agents in the Periodontal Pocket.

PubMed

Morelli, Laura; Cappelluti, Martino Alfredo; Ricotti, Leonardo; Lenardi, Cristina; Gerges, Irini

2017-08-01

Periodontitis treatments usually require local administration of antimicrobial drugs with the aim to reduce the bacterial load inside the periodontal pocket. Effective pharmaceutical treatments may require sustained local drug release for several days in the site of interest. Currently available solutions are still not able to fulfill the clinical need for high-quality treatments, mainly in terms of release profiles and patients' comfort. This work aims to fill this gap through the development of an in situ gelling system, capable to achieve controlled and sustained release of antimicrobial agents for medium-to-long-term treatments. The system is composed of micrometer-sized β-cyclodextrin-based hydrogel (bCD-Jef-MPs), featured by a strong hydrophilic character, suspended in a synthetic block-co-polymer solution (Poloxamer 407), which is capable to undergo rapid thermally induced sol-gel phase transition at body temperature. The chemical structure of bCD-Jef-MPs was confirmed by cross-correlating data from Fourier transform infrared (FTIR) spectroscopy, swelling test, and degradation kinetics. The thermally induced sol-gel phase transition is demonstrated by rheometric tests. The effectiveness of the described system to achieve sustained release of antimicrobial agents is demonstrated in vitro, using chlorhexidine digluconate as a drug model. The results achieved in this work disclose the potential of the mentioned system in effectively treating periodontitis lesions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of in vitro Hydrophilic and Hydrophobic Dual Drug Release from Polymeric Films Produced by Sodium alginate-MaterBi® Drying Emulsions.

PubMed

Setti, Chiara; Suarato, Giulia; Perotto, Giovanni; Athanassiou, Athanassia; Bayer, Ilker S

2018-06-18

Emulsions are known to be effective carriers of hydrophobic drugs, and particularly injectable emulsions have been successfully implemented for in vivo controlled drug release. Recently, high internal phase emulsions have also been used to produce porous polymeric templates for pharmaceutical applications. However, emulsions containing dissolved biopolymers both in the oil and water phases are very scarce. In this study, we demonstrate such an emulsion, in which the oil phase contains a hydrophobic biodegradable polymer, MaterBi ® , and the water phase is aqueous sodium alginate dispersion. The two phases were emulsified simply by ultrasonic processing without any surfactants. The emulsions were stable for several days and were dried into composite solid films with varying MaterBi ® /alginate fractions. The films were loaded with two model drugs, a hydrophilic eosin-based cutaneous antiseptic and the hydrophobic curcumin. Drug release capacity of the films was investigated in detail, and controlled release of each model drug was achieved either by tuning the polymer fraction in the films during emulsification or by crosslinking sodium alginate fraction of the films by calcium salt solution immersion. The emulsions can be formulated to carry either a single model drug or both drugs depending on the desired application. Films demonstrate excellent cell biocompatibility against human dermal fibroblast, adult cells. Copyright © 2018. Published by Elsevier B.V.

UV-visible spectroscopy as an alternative to liquid chromatography for determination of everolimus in surfactant-containing dissolution media: a useful approach based on solid-phase extraction.

PubMed

Kamberi, Marika; Tran, Thu-Ngoc

2012-11-01

High-throughput 96-well solid phase extraction (SPE) plate with C-18 reversed phase sorbent followed by UV-visible (UV-Vis) microplate reader was applied to the analysis of hydrophobic drugs in surfactant-containing dissolution media, which are often used to evaluate the in-vitro drug release of drug eluting stents (DES). Everolimus and dissolution medium containing Triton X-405 were selected as representatives, and the appropriate SPE conditions (adsorption, washing and elution) were investigated to obtain a practical and reliable sample clean-up. It was shown that the developed SPE procedure was capable of removing interfering components (Triton X-405 and its impurities), allowing for an accurate automated spectrophotometric analysis to be performed. The proposed UV-Vis spectrophotometric method yielded equivalent results compared to a classical LC analysis method. Linear regression analysis indicated that both methods have the ability to obtain test results that are directly proportional to the concentration of analyte in the sample within the selected range of 1.0-10 μg/ml for everolimus, with a coefficient of correlation (r(2)) value of >0.998 and standard deviation of the residuals (Syx) of <2%. The individual recoveries of everolimus ranged from 97 to 104% for the UV-Vis spectrophotometric method and from 98 to 102 for the HPLC method, respectively. The 95% CI of the mean recovery for the UV-Vis spectrophotometric method was 99-102% and for the HPLC method was 99-101%. No statistical difference was found between the mean recoveries of the methods (p=0.42). Hence the methods are free from interference due to Triton and other chemicals present in the dissolution medium. The variation in the amount of everolimus estimated by UV-Vis spectrophotometric and HPLC methods was ≤3.5%, and the drug release profiles obtained by both methods were found to be equivalent by evaluation with two-one-sided t-test (two-tailed, p=0.62; mean of differences, 0.17; 95% CI, 0.62-0.96) and similarity factor f2 (f2 value, 87). The excellent conformity of the results makes UV-Vis spectrophotometer an ideal tool for analyzing the drugs in the media containing surfactants, after SPE. The 96-well SPE plates in combination with UV-Vis microplate reader provide a high throughput method for the determination of in-vitro drug release profile of DES. Switching from HPLC to UV-Vis spectrophotometer microplate reader assay reduces the solvent consumption and labor required for the sample analyses. This directly impacts the profitability of the laboratory. Copyright © 2012 Elsevier B.V. All rights reserved.

Composition and emission dynamics of migratory locust volatiles in response to changes in developmental stages and population density.

PubMed

Wei, Jianing; Shao, Wenbo; Wang, Xianhui; Ge, Jin; Chen, Xiangyong; Yu, Dan; Kang, Le

2017-02-01

Chemical communication plays an important role in density-dependent phase change in locusts. However, the volatile components and emission patterns of the migratory locust, Locusta migratoria, are largely unknown. In this study, we identified the chemical compositions and emission dynamics of locust volatiles from the body and feces and associated them with developmental stages, sexes and phase changes. The migratory locust shares a number of volatile components with the desert locust (Schistocerca gregaria), but the emission dynamics of the two locust species are significantly different. The body odors of the gregarious nymphs in the migratory locust consisted of phenylacetonitrile (PAN), benzaldehyde, guaiacol, phenol, aliphatic acids and 2,3-butanediol, and PAN was the dominant volatile. Volatiles from the fecal pellets of the nymphs primarily consist of guaiacol and phenol. Principal component analysis (PCA) showed significant differences in the volatile profiles between gregarious and solitary locusts. PAN and 4-vinylanisole concentrations were significantly higher in gregarious individuals than in solitary locusts. Gregarious mature males released significantly higher amounts of PAN and 4-vinylanisole during adulthood than mature females and immature adults of both sexes. Furthermore, PAN and 4-vinylanisole were completely lost in gregarious nymphs during the solitarization process, but were obtained by solitary nymphs during gregarization. The amounts of benzaldehyde, guaiacol and phenol only unidirectionally decreased from solitary to crowded treatment. Aliphatic aldehydes (C7 to C10), which were previously reported as locust volatiles, are now identified as environmental contaminants. Therefore, our results illustrate the precise odor profiles of migratory locusts during developmental stages, sexes and phase change. However, the function and role of PAN and other aromatic compounds during phase transition need further investigation. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

PubMed

Lagarce, F; Cruaud, O; Deuschel, C; Bayssas, M; Griffon-Etienne, G; Benoit, J

2002-08-21

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

SU-E-T-405: Evaluation of the Raystation Electron Monte Carlo Algorithm for Varian Linear Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sansourekidou, P; Allen, C

2015-06-15

Purpose: To evaluate the Raystation v4.51 Electron Monte Carlo algorithm for Varian Trilogy, IX and 2100 series linear accelerators and commission for clinical use. Methods: Seventy two water and forty air scans were acquired with a water tank in the form of profiles and depth doses, as requested by vendor. Data was imported into Rayphysics beam modeling module. Energy spectrum was modeled using seven parameters. Contamination photons were modeled using five parameters. Source phase space was modeled using six parameters. Calculations were performed in clinical version 4.51 and percent depth dose curves and profiles were extracted to be compared tomore » water tank measurements. Sensitivity tests were performed for all parameters. Grid size and particle histories were evaluated per energy for statistical uncertainty performance. Results: Model accuracy for air profiles is poor in the shoulder and penumbra region. However, model accuracy for water scans is acceptable. All energies and cones are within 2%/2mm for 90% of the points evaluated. Source phase space parameters have a cumulative effect. To achieve distributions with satisfactory smoothness level a 0.1cm grid and 3,000,000 particle histories were used for commissioning calculations. Calculation time was approximately 3 hours per energy. Conclusion: Raystation electron Monte Carlo is acceptable for clinical use for the Varian accelerators listed. Results are inferior to Elekta Electron Monte Carlo modeling. Known issues were reported to Raysearch and will be resolved in upcoming releases. Auto-modeling is limited to open cone depth dose curves and needs expansion.« less

An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier.

PubMed

Vasiljevic, Dragana; Parojcic, Jelena; Primorac, Marija; Vuleta, Gordana

2006-02-17

Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were prepared using relatively low concentrations of lipophilic polymeric primary emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a model drug. The investigated formulations were characterized and their stability over the time was evaluated by dynamic and oscillatory rheological measurements, microscopic analysis and in vitro drug release study. In vitro release profiles of the selected model drug were evaluated in terms of the effective diffusion coefficients and flux of the released drug. The multiple emulsion samples exhibited good stability during the ageing time. Concentration of the lipophilic primary emulsifier markedly affected rheological behaviour as well as the droplet size and in vitro drug release kinetics of the investigated systems. The multiple emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier had the lowest droplet size and the highest apparent viscosity and highest elastic characteristics. Drug release data indicated predominately diffusional drug release mechanism with sustained and prolonged drug release accomplished with 2.4% (w/w) of lipophilic emulsifier employed.

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core-Shell, Multilayer, and Gradient Concentration Profiles.

PubMed

Haring, Alexander P; Tong, Yuxin; Halper, Justin; Johnson, Blake N

2018-06-10

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

PubMed

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc.

Long-term Controlled Drug Release from bi-component Electrospun Fibers

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

In vitro-in vivo correlation for nevirapine extended release tablets.

PubMed

Macha, Sreeraj; Yong, Chan-Loi; Darrington, Todd; Davis, Mark S; MacGregor, Thomas R; Castles, Mark; Krill, Steven L

2009-12-01

An in vitro-in vivo correlation (IVIVC) for four nevirapine extended release tablets with varying polymer contents was developed. The pharmacokinetics of extended release formulations were assessed in a parallel group study with healthy volunteers and compared with corresponding in vitro dissolution data obtained using a USP apparatus type 1. In vitro samples were analysed using HPLC with UV detection and in vivo samples were analysed using a HPLC-MS/MS assay; the IVIVC analyses comparing the two results were performed using WinNonlin. A Double Weibull model optimally fits the in vitro data. A unit impulse response (UIR) was assessed using the fastest ER formulation as a reference. The deconvolution of the in vivo concentration time data was performed using the UIR to estimate an in vivo drug release profile. A linear model with a time-scaling factor clarified the relationship between in vitro and in vivo data. The predictability of the final model was consistent based on internal validation. Average percent prediction errors for pharmacokinetic parameters were <10% and individual values for all formulations were <15%. Therefore, a Level A IVIVC was developed and validated for nevirapine extended release formulations providing robust predictions of in vivo profiles based on in vitro dissolution profiles. Copyright 2009 John Wiley & Sons, Ltd.

Effect of cosmetic matrices on the release and odour profiles of the supercritical CO2 extract of Origanum majorana L.

PubMed

Costa, P; Velasco, C V; Loureiro, J M; Rodrigues, A E

2016-08-01

In this study, the effect of different cosmetic matrices on the release profile and odour intensity of the fragrance O. majorana was investigated for the first time. The fragrance compounds of O. majorana were extracted by supercritical fluid extraction using carbon dioxide (SFE-CO2 ) at 40°C and two operating pressures (8.5 and 10 MPa), and their chemical profiles were assessed by gas chromatography with flame ionization detector coupled with mass spectrometry (GC-FID/MS). Lastly, the fragrance compounds were incorporated into three cosmetic matrices (glycerine, dipropylene glycol and skin lotion) to assess their release and odour profiles over time using dynamic headspace (DHS)/GC-FID/MS and Odour Value concept, respectively. The SFE-CO2 enabled recovering extracts with the pleasant scent of the living plant, and the increment of pressure induced an increase on the extraction yield. GC-FID/MS analyses revealed that oxygen-containing monoterpenes was the principal group of components identified in both SFE-CO2 extracts. The fragrance compounds were more retained in dipropylene glycol, and the major deviations from the original odour intensity (control) were observed in the presence of dipropylene glycol and skin lotion. The hydrophilic character of the cosmetic matrices strongly influenced the release of the fragrance compounds, thus affecting the odour profile of the studied mixtures. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A detailed view of microparticle formation by in-process monitoring of the glass transition temperature.

PubMed

Vay, Kerstin; Frieß, Wolfgang; Scheler, Stefan

2012-06-01

Biodegradable poly(D,L-lactide-co-glycolide) microspheres were prepared by a well-controlled emulsion solvent extraction/evaporation process. The objective of this study was to investigate how drug release can be modified by changing the morphology of the polymer matrix. The matrix structure was controlled by the preparation temperature which was varied between 10 and 35 °C, thus changing the 4 weeks release pattern from almost linear kinetics to a sigmoidal profile with a distinct lag phase and furthermore decreasing the encapsulation efficiency. By monitoring the glass transition temperature during the extraction process, it was shown that the preparation temperature determines the particle morphology by influencing the time span in which the polymer chains were mobile and flexible during the extraction process. Further factors determining drug release were found to be the molecular weight of the polymer and the rate of solvent removal. The latter, however, has also influence on the encapsulation efficiency with slow removal causing a higher drug loss. A secondary modification of the outer particle structure could be achieved by ethanolic post-treatment of the particles, which caused an extension of the lag phase and subsequently an accelerated drug release. Copyright © 2012. Published by Elsevier B.V.

A Comprehensive Tool and Analytical Pathway for Differential Molecular Profiling and Biomarker Discovery

DTIC Science & Technology

2014-10-20

three possiblities: AKR , B6, and BALB_B) and MUP Protein (containing two possibilities: Intact and Denatured), then you can view a plot of the Strain...the tags for the last two labels. Again, if the attribute Strain has three tags: AKR , B6, 74 Distribution A . Approved for public release...AFRL-RH-WP-TR-2014-0131 A COMPREHENSIVE TOOL AND ANALYTICAL PATHWAY FOR DIFFERENTIAL MOLECULAR PROFILING AND BIOMARKER DISCOVERY

Influence of osmotic stress on the profile and gene expression of surface layer proteins in Lactobacillus acidophilus ATCC 4356.

PubMed

Palomino, María Mercedes; Waehner, Pablo M; Fina Martin, Joaquina; Ojeda, Paula; Malone, Lucía; Sánchez Rivas, Carmen; Prado Acosta, Mariano; Allievi, Mariana C; Ruzal, Sandra M

2016-10-01

In this work, we studied the role of surface layer (S-layer) proteins in the adaptation of Lactobacillus acidophilus ATCC 4356 to the osmotic stress generated by high salt. The amounts of the predominant and the auxiliary S-layer proteins SlpA and SlpX were strongly influenced by the growth phase and high-salt conditions (0.6 M NaCl). Changes in gene expression were also observed as the mRNAs of the slpA and slpX genes increased related to the growth phase and presence of high salt. A growth stage-dependent modification on the S-layer protein profile in response to NaCl was observed: while in control conditions, the auxiliary SlpX protein represented less than 10 % of the total S-layer protein, in high-salt conditions, it increased to almost 40 % in the stationary phase. The increase in S-layer protein synthesis in the stress condition could be a consequence of or a way to counteract the fragility of the cell wall, since a decrease in the cell wall thickness and envelope components (peptidoglycan layer and lipoteichoic acid content) was observed in L. acidophilus when compared to a non-S-layer-producing species such as Lactobacillus casei. Also, the stationary phase and growth in high-salt medium resulted in increased release of S-layer proteins to the supernatant medium. Overall, these findings suggest that pre-growth in high-salt conditions would result in an advantage for the probiotic nature of L. acidophilus ATCC 4356 as the increased amount and release of the S-layer might be appropriate for its antimicrobial capacity.

Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories.

PubMed

Chicco, D; Grabnar, I; Skerjanec, A; Vojnovic, D; Maurich, V; Realdon, N; Ragazzi, E; Belic, A; Karba, R; Mrhar, A

1999-11-05

An in vivo investigation of paracetamol availability was carried out on eight healthy volunteers, comparing two paracetamol suppository formulations prepared using two different gliceride bases, a fast drug-releasing one and a slow drug-releasing one, i.e. Witepsol H15 and W35, respectively. The formulations were selected on the basis of a previous in vitro drug release study, which showed that, by superimposing the excipients in two layers within the same suppository, the drug release kinetics could be modulated using different ratios between the two layers. The comparison between the two different formulations in terms of plasma profiles and total amounts of drug excreted in urine revealed an increase in the extent of drug absorption from the layered excipient suppository. As the W35 has a higher monoglyceride content than the H15, this improved paracetamol availability could be ascribed to the absorption-enhancing effect of the monoglycerides. Moreover, the W35 has also a higher viscosity, which could possibly cause the suppository to be retained for a longer time in the lower part of the rectum, where the blood is drained directly to the systemic circulation. It was therefore hypothesized that the enhanced paracetamol availability could be also due to a liver bypass mechanism. For a further examination of the paracetamol absorption kinetics after rectal administration, a one-compartment model was fitted to the drug plasma concentration data. This approach allowed to draw absorption versus time profiles, which showed that a retardation actually occurred in paracetamol absorption when using suppositories containing the slow drug releasing excipient W35. These absorption data were then employed for an A level in vitro-in vivo correlation testing, and a linear relationship was found between in vitro release rate and in vivo absorption rate, both for fast releasing and for the layered excipient suppositories.

Understanding Drug Release Data through Thermodynamic Analysis.

PubMed

Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda E; Genre, Julieta; Oliveira, Anselmo Gomes de; Egito, Eryvaldo Sócrates Tabosa do

2017-06-13

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas-Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

Understanding Drug Release Data through Thermodynamic Analysis

PubMed Central

Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda e; Genre, Julieta; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Sócrates Tabosa

2017-01-01

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability. PMID:28773009

Anisotropic properties of phase separation in two-component dipolar Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Wang, Wei; Li, Jinbin

2018-03-01

Using Crank-Nicolson method, we calculate ground state wave functions of two-component dipolar Bose-Einstein condensates (BECs) and show that, due to dipole-dipole interaction (DDI), the condensate mixture displays anisotropic phase separation. The effects of DDI, inter-component s-wave scattering, strength of trap potential and particle numbers on the density profiles are investigated. Three types of two-component profiles are present, first cigar, along z-axis and concentric torus, second pancake (or blood cell), in xy-plane, and two non-uniform ellipsoid, separated by the pancake and third two dumbbell shapes.

Effects of crosslinking on the mechanical properties, drug release and cytocompatibility of protein polymers.

PubMed

Martinez, Adam W; Caves, Jeffrey M; Ravi, Swathi; Li, Wehnsheng; Chaikof, Elliot L

2014-01-01

Recombinant elastin-like protein polymers are increasingly being investigated as component materials of a variety of implantable medical devices. This is chiefly a result of their favorable biological properties and the ability to tailor their physical and mechanical properties. In this report, we explore the potential of modulating the water content, mechanical properties, and drug release profiles of protein films through the selection of different crosslinking schemes and processing strategies. We find that the selection of crosslinking scheme and processing strategy has a significant influence on all aspects of protein polymer films. Significantly, utilization of a confined, fixed volume, as well as vapor-phase crosslinking strategies, decreased protein polymer equilibrium water content. Specifically, as compared to uncrosslinked protein gels, water content was reduced for genipin (15.5%), glutaraldehyde (GTA, 24.5%), GTA vapor crosslinking (31.6%), disulfide (SS, 18.2%) and SS vapor crosslinking (25.5%) (P<0.05). Distinct crosslinking strategies modulated protein polymer stiffness, strain at failure and ultimate tensile strength (UTS). In all cases, vapor-phase crosslinking produced the stiffest films with the highest UTS. Moreover, both confined, fixed volume and vapor-phase approaches influenced drug delivery rates, resulting in decreased initial drug burst and release rates as compared to solution phase crosslinking. Tailored crosslinking strategies provide an important option for modulating the physical, mechanical and drug delivery properties of protein polymers. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An empirical model for dissolution profile and its application to floating dosage forms.

PubMed

Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul

2014-06-02

A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxic industrial chemical (TIC) source emissions modeling for pressurized liquefied gases

NASA Astrophysics Data System (ADS)

Britter, Rex; Weil, Jeffrey; Leung, Joseph; Hanna, Steven

2011-01-01

The objective of this article is to report current toxic industrial chemical (TIC) source emissions formulas appropriate for use in atmospheric comprehensive risk assessment models so as to represent state-of-the-art knowledge. The focus is on high-priority scenarios, including two-phase releases of pressurized liquefied gases such as chlorine from rail cars. The total mass released and the release duration are major parameters, as well as the velocity, thermodynamic state, and amount and droplet sizes of imbedded aerosols of the material at the exit of the rupture, which are required as inputs to the subsequent jet and dispersion modeling. Because of the many possible release scenarios that could develop, a suite of model equations has been described. These allow for gas, two-phase or liquid storage and release through ruptures of various types including sharp-edged and "pipe-like" ruptures. Model equations for jet depressurization and phase change due to flashing are available. Consideration of the importance of vessel response to a rupture is introduced. The breakup of the jet into fine droplets and their subsequent suspension and evaporation, or rainout is still a significant uncertainty in the overall modeling process. The recommended models are evaluated with data from various TIC field experiments, in particular recent experiments with pressurized liquefied gases. It is found that there is typically a factor of two error in models compared with research-grade observations of mass flow rates. However, biases are present in models' estimates of the droplet size distributions resulting from flashing releases.

Comparative studies on the properties of glycyrrhetinic acid-loaded PLGA microparticles prepared by emulsion and template methods.

PubMed

Wang, Hong; Zhang, Guangxing; Sui, Hong; Liu, Yanhua; Park, Kinam; Wang, Wenping

2015-12-30

The O/W emulsion method has been widely used for the production of poly (lactide-co-glycolide) (PLGA) microparticles. Recently, a template method has been used to make homogeneous microparticles with predefined size and shape, and shown to be useful in encapsulating different types of active compounds. However, differences between the template method and emulsion method have not been examined. In the current study, PLGA microparticles were prepared by the two methods using glycyrrhetinic acid (GA) as a model drug. The properties of obtained microparticles were characterized and compared on drug distribution, in vitro release, and degradation. An encapsulation efficiency of over 70% and a mean particle size of about 40μm were found for both methods. DSC thermograms and XRPD diffractograms indicated that GA was highly dispersed or in the amorphous state in the matrix of microparticles. The emulsion method produced microparticles of a broad size distribution with a core-shell type structure and many drug-rich domains inside each microparticle. Its drug release and matrix degradation was slow before Day 50 and then accelerated. In contrast, the template method formed microparticles with narrow size distribution and drug distribution without apparent drug-rich domains. The template microparticles with a loading efficiency of 85% exhibited a zero-order release profile for 3 months after the initial burst release of 26.7%, and a steady surface erosion process as well. The same microparticles made by two different methods showed two distinguished drug release profiles. The two different methods can be supplementary with each other in optimization of drug formulation for achieving predetermined drug release patterns. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiation Budget Profiles measured through the Atmosphere with a Return Glider Radiosonde

NASA Astrophysics Data System (ADS)

Philipona, R.; Kraeuchi, A.; Kivi, R.

2015-12-01

Very promising radiation budget profile measurements through the atmosphere were made in 2011 with a balloon borne short- and longwave net radiometer. New and improved radiation sensors from Kipp&Zonen are now used in a glider aircraft together with a standard Swiss radiosonde from Meteolabor AG. This new return glider radiosonde (RG-R), is lifted up with double balloon technique to prevent pendulum motion and to keep the radiation instruments as horizontal as possible during the ascent measuring phase. The RG-R is equipped with a release mechanism and an autopilot that flies the glider radiosonde back to the launch site, or to a predefined open space, where it releases a parachute for landing once it is 100 meter above ground. The RG-R was successfully tested and deployed for tropospheric and stratospheric radiation measurements up to 30 hPa (24 km altitude) at the GRUAN sites Payerne (Switzerland) and Sodankylä (Finland). Radiation profiles and the radiation budget through the atmosphere during different daytimes and under cloud-free and cloudy situations will be shown in relation to temperature and humidity at the surface and in the atmosphere. The RG-R flight characteristics and new measurement possibilities will also be discussed.

Controlling protein release using biodegradable microparticles

NASA Astrophysics Data System (ADS)

Kline, Benjamin Patrick

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Simulation of Tracer Concentration Data in the Brush Creek Drainage Flow Using an Integrated Puff Model.

NASA Astrophysics Data System (ADS)

Rao, K. Shankar; Eckman, Richard M.; Hosker, Rayford P., Jr.

1989-07-01

During the 1984 ASCOT field study in Brush Creek Valley, two perfluorocarbon tracers were released into the nocturnal drainage flow at two different heights. The resulting surface concentrations were sampled at 90 sites, and vertical concentration profiles at 11 sites. These detailed tracer measurements provide a valuable dataset for developing and testing models of pollutant transport and dispersion in valleys.In this paper, we present the results of Gaussian puff model simulations of the tracer releases in Brush Creek Valley. The model was modified to account for the restricted lateral dispersion in the valley, and for the gross elevation differences between the release site and the receptors. The variable wind fields needed to transport the puffs were obtained by interpolation between wind profiles measured using tethered balloons at five along-valley sites. Direct turbulence measurements were used to estimate diffusion. Subsidence in the valley flow was included for elevated releases.Two test simulations-covering different nights, tracers, and release heights-were performed. The predicted hourly concentrations were compared with observations at 51 ground-level locations. At most sites, the predicted and observed concentrations agree within a factor of 2 to 6. For the elevated release simulation, the observed mean concentration is 40 pL/L, the predicted mean is 21 pL/L, the correlation coefficient between the observed and predicted concentrations is 0.24, and the index of agreement is 0.46. For the surface release simulation, the observed mean is 85 pL/L, and the predicted mean is 73 pL/L. The correlation coefficient is 0.23, and the index of agreement is 0.42. The results suggest that this modified puff model can be used as a practical tool for simulating pollutant transport and dispersion in deep valleys.

A new approach to assess the skier additional stress within a multi-layered snowpack

NASA Astrophysics Data System (ADS)

Monti, Fabiano; Gaume, Johan; van Herwijnen, Alec; Schweizer, Jürg

2014-05-01

The physical and mechanical processes of dry-snow slab avalanche formation can be distinguished into two subsequent phases: failure initiation and crack propagation. Several approaches tried to quantify slab avalanche release probability in terms of failure initiation, based on a simple strength-of-material approach (strength vs. stress). Even if it is known that both weak layer and slab properties play a major role in avalanche release, apart from weak layer characteristics, often only the slab thickness and its average density were considered. For calculating the amount of additional stress (e.g. due to a skier) at the depth of the weak layer, the snow cover was often assumed to be a semi-infinite elastic half space in order to apply Boussinesq's theory. However, finite element (FE) calculations have shown that slab layering strongly influences the stress at depth. To avoid FE calculations, we suggest a new approach based on a simplification of multi-layered elasticity theory. It allows computing the additional stress due to a skier at the depth of the weak layer, taking into account the layering of the snow slab and the substratum. The proposed approach was first tested on simplified snow profiles and compared reasonably well with FE calculations. We then implemented the method to refine the classical skier stability index. Using manually observed snow profiles, classified in different stability classes using stability tests, we obtained a satisfactory discrimination power. Lastly, the refined skier stability index was implemented into the 1-D snow cover model SNOWPACK and presented on two case studies. In the future, it will be interesting to implement the proposed method for describing skier-induced stress within a multi-layered snowpack into more complex models which take into account not only failure initiation but also crack propagation.

Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

NASA Astrophysics Data System (ADS)

Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

2015-09-01

Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

Spectroscopic and chemical-kinetic analysis of the phases of HCCI autoignition and combustion for single- and two-stage ignition fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Wontae; Dec, John; Sjoeberg, Magnus

The temporal phases of autoignition and combustion in an HCCI engine have been investigated in both an all-metal engine and a matching optical engine. Gasoline, a primary reference fuel mixture (PRF80), and several representative real-fuel constituents were examined. Only PRF80, which is a two-stage ignition fuel, exhibited a ''cool-flame'' low-temperature heat-release (LTHR) phase. For all fuels, slow exothermic reactions occurring at intermediate temperatures raised the charge temperature to the hot-ignition point. In addition to the amount of LTHR, differences in this intermediate-temperature heat-release (ITHR) phase affect the fuel ignition quality. Chemiluminescence images of iso-octane show a weak and uniform lightmore » emission during this phase. This is followed by the main high-temperature heat-release (HTHR) phase. Finally, a ''burnout'' phase was observed, with very weak uniform emission and near-zero heat-release rate (HRR). To better understand these combustion phases, chemiluminescence spectroscopy and chemical-kinetic analysis were applied for the single-stage ignition fuel, iso-octane, and the two-stage fuel, PRF80. For both fuels, the spectrum obtained during the ITHR phase was dominated by formaldehyde chemiluminescence. This was similar to the LTHR spectrum of PRF80, but the emission intensity and the temperature were much higher, indicating differences between the ITHR and LTHR phases. Chemical-kinetic modeling clarified the differences and similarities between the LTHR and ITHR phases and the cause of the enhanced ITHR with PRF80. The HTHR spectra for both fuels were dominated by a broad CO continuum with some contribution from bands of HCO, CH, and OH. The modeling showed that the CO+ O{yields}CO{sub 2}+h{nu} reaction responsible for the CO continuum emission tracks the HTHR well, explaining the strong correlation observed experimentally between the total chemiluminescence and HRR during the HTHR phase. It also showed that the CO continuum does not contribute to the ITHR and LTHR chemiluminescence. Bands of H{sub 2}O and O{sub 2} in the red and IR regions were also detected during the HTHR, which the data indicated were most likely due to thermal excitation. The very weak light emission in the ''burnout'' phase also appeared to be thermal emission from H{sub 2}O and O{sub 2}. (author)« less

Heterogeneous UO2 fuel irradiated up to a high burn-up: Investigation of the HBS and of fission product releases

NASA Astrophysics Data System (ADS)

Noirot, J.; Lamontagne, J.; Nakae, N.; Kitagawa, T.; Kosaka, Y.; Tverberg, T.

2013-11-01

A UO2 fuel with a heterogeneous distribution of 235U was irradiated up to a high burn-up in the Halden Boiling Water Reactor (HBWR). The last 100 days of irradiation were performed with an increased level of linear power. The effect of the heterogeneous fissile isotope distribution on the formation of the HBS was studied free of the possible influence of Pu which exists in heterogeneous MOX fuels. The HBS formed in 235U-rich agglomerates and its main characteristics were very similar to those of the HBS formed in Pu-rich agglomerates of heterogeneous MOX fuels. The maximum local contents of Nd and Xe before HBS formation were studied in this fuel. In addition to a Pu effect that promotes the HBS phenomenon, comparison with previous results for heterogeneous MOX fuels showed that the local fission product concentration was not the only parameter that has to be taken into consideration. It appears that the local actinide depletion by fission and/or the energy locally deposited through electronic interactions in the fission fragment recoils also have an effect on the HBS formation threshold. Moreover, a major release of fission gases from the peripheral 235U-rich agglomerates of HBS bubbles and a Cs radial movement are also evidenced in this heterogeneous UO2. Cs deposits on the peripheral grain boundaries, including the HBS grain boundaries, are considered to reveal the release paths. SUP>235U-rich agglomerates, SUP>235U-poor areas, an intermediate phase with intermediate 235U concentrations. Short fuel rods were fabricated with these pellets. The main characteristics of these fuel rods are shown in Table 1.These rods were irradiated to high burn-ups in the IFA-609/626 of the HBWR and then one was irradiated in the IFA-702 for 100 days. Fig. 2 shows the irradiation history of this fuel. The final average burn-up of the rod was 69 GWd/tU. Due to the flux differences along the rod, however, the average burn-up of the cross section examined was 63 GWd/tU. This fuel experienced high linear powers during the first year of irradiation, but at the end of the IFA-609/626 period, the average linear power of the rod was around 12 kW/m. In the IFA-702, the power was gradually increased over 7 days from 12 kW/m to 22.5 kW/m before it was decreased again to reach ˜19 kW/m at the end of the 100 days forming this part of the irradiation. A LEICA (DM RXA2) optical microscope. A shielded electronic microprobe (EPMA) SX-100R by CAMECA. A shielded scanning electron microscope (SEM): the Philips XL30. Image acquisitions were performed using the ADDA "SIS" system with the AnalySIS software for image analysis. A shielded secondary ion mass spectrometer (SIMS): the CAMECA IMS 6f was capable of analysing the same samples as the SEM and EPMA [16-22]. In the central part of the pellet for all three phases, Xe precipitated into bubbles with very little Xe remaining outside the bubbles. Some Xe-filled bubbles were detected under the surface in this area. They appear as bright spots. Around mid-radius on the periphery of the 235U-poor areas and in the intermediate phase, Xe was depleted on the periphery of the grains. This depletion was not associated with Xe-filled bubbles that would be detected under the polished surface. Moreover, no large intergranular open bubbles were visible. Therefore, this missing gas must have been released. In the 235U-rich agglomerates all over the section, Xe precipitated into bubbles with very little Xe remaining outside the bubbles. The Xe quantitative analyses through 235U-rich agglomerates on the pellet periphery (Fig. 9) confirmed the low quantity of Xe remaining outside the bubbles. This Xe content was around 0.1 wt%. Fig. 10 shows the Xe and Nd EPMA quantitative measurements along a radius of the cross section. In this figure and in Fig. 9, the weight percentage scales were set so that the two profiles would be almost identical without Xe release or precipitation. Along the Xe axis, the Nd profile can be considered as the local Xe production. Fig. 10 shows that the Xe measurement all through the central part is low except for a few points corresponding to unopened but close to the polished surface and detected by EPMA. These points correspond to the bright spots detected in the central part in Fig. 8. High concentrations were detected locally all over the radius on the Nd profile. They correspond to the 235U-rich agglomerates or their surroundings. Outside the central part, these high Nd concentrations correspond to low Xe concentrations, consistent with the maps in Fig. 8 and the detailed analyses across large 235U-rich agglomerates (Fig. 9).Fig. 11 shows a set of Xe (wt%) and (145Nd + 146Nd)/heavy metal radial profiles both acquired by SIMS. Three profiles are show for each set: one in the 235U-rich agglomerates, one in the 235U-poor areas and one in the intermediate phase. The three phases are not homogeneous themselves. This induces differences between (145Nd + 146Nd)/HM SIMS measurement points of a given phase. The (145Nd + 146Nd)/HM results are a reference for the Xe measurements, giving an estimation of the relative Xe local production. The (145Nd + 146Nd)/HM was high in the 235U-rich agglomerates, lower in the intermediate phase and even lower in the 235U-poor areas. Differences similar to those obtained herein between the phases would have been found in the Xe measurements if no release had occurred in any of those phases. The Xe (wt%) results show that this is not the case. The Xe measurements were quite similar in the intermediate phase and in the 235U-poor areas; they would have been higher in the intermediate phase if no release had occurred. The Xe measurements in the 235U-rich agglomerates were very low and lower than in the two other phases. For the 235U-rich agglomerates, there was a very big difference, across the entire radius, between the Xe measured and the Xe local production.In the SIMS Xe measurements, local depth profiles show peaks on a base line [19]. The base line corresponds to the solid solution Xe and to the nano-bubbles. The peaks correspond to Xe in larger bubbles opened by ion beam fuel sputtering. The SIMS total values correspond to the Xe outside these bubbles plus the Xe trapped in these bubbles.Fig. 12 shows the total Xe SIMS results (already shown in Fig. 11) together with the base line measurements for each measurement point and in separate graphs for each phase. The Xe EPMA quantitative measurements used as a background for these three graphs are the same as those in Fig. 10 and are the same for the three graphs, without any phase distinction. The SIMS Xe relative measurements were calibrated through a correspondence between the SIMS base line results and the EPMA measurements [20]. As expected, the SIMS base line profile was consistent with the EPMA all along the profile for each corresponding phase. For example, the SIMS base line in the 235U-rich agglomerates corresponds to the low EPMA measurement points of the Xe in this zone, i.e. the points of the EPMA profile in the 235U-rich agglomerates. By way of comparison between the Xe and the Nd measurements (the latter being rescaled to be representative of the creation level of Xe), Fig. 11 made it possible to identify two main parts on the Xe SIMS radius: The central part 0R to ˜0.5R: In the intermediate phase and the 235U-poor areas, the SIMS total was used to identify this part as a release area. The average fraction of gas measured in the bubbles (the ratio between the gas in the bubbles and the total measurement) was between 60% and 90%. The Xe content outside the bubbles was very low. In the 235U-rich agglomerates, the SIMS total represents only a small fraction of the produced Xe, which means that a large fraction of the Xe is released or not detected by SIMS due to the large size of some agglomerate bubbles compared with the volume of the crater analysed. sim;0.5R to ˜1R: The 235U-poor areas are not release areas. The fraction of gas in bubbles measured in these areas remained low, ˜5%. The intermediate phase is a release area with moderate release. The average fraction of gas measured in the bubbles was around 20%. In the 235U-rich agglomerates, the Xe SIMS total was very low. This part is a release area. Sharp transitions between initial microstructure and the HBS, often inside one grain. Increase in the resulting grain size with increasing distance from the pellet periphery. The grain sizes are in fact consistent with the MOX measurements [2]. Increase in the bubble size with the increasing distance from the pellet periphery, consistent with the MOX measurements. Smaller bubbles tend to be found in the peripheral part of the 235U-rich agglomerates rather than in their central part. Sharp transition, around 0.5R, between the peripheral area where the conventional form of HBS forms in the 235U-rich agglomerates and the central part where much larger bubbles form and where the grain size is also clearly larger. Xe concentration of 0.1 wt% outside the bubbles in the HBS areas is consistent with the [2] MOX measurements at equivalent local burn-ups. The heterogeneous MOX fuels examinations have firmly established that the HBS can extend outside the Pu-rich agglomerates due to the implantation of fission products around these agglomerates. Similarly, it has been shown that the small Pu-rich agglomerates can remain with the initial microstructure even if there is a similar actual local burn-up, a large rate of fission products being implanted outside the agglomerates themselves so that the local fission product concentration remains low.In this 235U heterogeneous UO2, the Xe and Nd concentration levels reached at the HBS formation limit ranged between 0.8 wt% and 1.1 wt% for Xe and between 0.63 wt% and 0.83 wt% for Nd. These ranges are similar to what was reported in [23] for the UO2 rim. These limits are, however, slightly higher than those found for Pu-rich agglomerates in heterogeneous MOX fuels in [2] or in [24]. Nonetheless, they are clearly lower than the concentrations reached without HBS in the special Pu-poor spots in [2]. In these spots, UO2 particles in heterogeneous MOX were really close or even surrounded by Pu-rich areas. As a result, their fission product content, due to recoil, was almost the same as that in the surrounding Pu-rich agglomerates themselves despite a very low actual local burn-up. In these special UO2 spots in MOX fuel, 1.4 wt% was reached for Xe and no HBS formed.If these high Xe concentrations without HBS in the special spots in [2] were made possible by the very low Pu local concentration only, very high Xe concentrations should have been common around the heterogeneous UO2 fuel 235U-rich agglomerates, since the Pu level was low everywhere in this fuel. This is not what was observed.Even if this effect due to a high fission product level reached without the formation of a HBS (as reported in [2] for heterogeneous MOX fuels in the special spots) is partially due to the very low local Pu level, it does not seem to be the only reason. It also seems to be partly due to the very low level of actual fissions occurring there. Between a rich agglomerate and such a highly implanted area there is: The same local fission product build-up and associated damage (due to cascades from the nuclei interactions during the last part of the fission fragment recoil). A large difference in the actinide isotope depletion to the extent that a difference in chemical composition exists between the two. A difference in the electronic excitation level at the beginning of the fission fragment recoil, higher in Pu agglomerates and in 235U-rich agglomerates than in the low fissile content areas, even surrounded by rich areas. The last two points may have an effect on the formation of a HBS though this paper cannot say which one is the most significant.The highest levels reached for Xe and Nd without HBS in the 235U heterogeneous fuel are very likely to correspond to places where the initial 235U content was particularly low but where fission recoil led to these high levels. The maximum concentrations of fission products reached before the formation of a HBS in the 235U heterogeneous fuel are lower than for the heterogeneous MOX special Pu-poor spots. This is most certainly due to the local 235U initial concentration in the 235U-poor areas which is nonetheless high when compared with the initial Pu concentrations in the Pu-poor areas in the MOX fuel. Consequently, there are more fission reactions there in the heterogeneous UO2 fuel than in the MOX fuel.This fission and/or fission spike effect has in fact little impact on the overall fuel behaviour, be it homogeneous or heterogeneous, but it has to be taken into account in the separate-effect experiments where unirradiated UO2 is submitted to ion irradiation to simulate the irradiation effects [9,25-30]. The depletion of the actinide isotopes cannot be simulated in these experiments. The IFA-702 re-irradiation, with the high power during the last period of the irradiation most certainly having played a role. The other major difference between this fuel was irradiated under BWR conditions, whereas those used in [2] were all PWR fuels. The images of the IFA-702 heterogeneous UO2 fuel on the periphery show that an internal zirconia layer was formed during the irradiation, which is a sign of gap closure under hot conditions, though a thin gap was still measured at room temperature. Therefore, the stress field in the pellet of this fuel must have been significantly different from that of the fuel used in [2]. The resulting release is all the more interesting since the release path is more or less revealed by the Cs deposits. This Cs is released from the hot central part of the pellet and is not only in the fuel-cladding gap and along the obvious radial cracks, but also in: All the grain boundaries around those radial cracks. The HBS 235U-rich agglomerates around those radial cracks. Like for Xe, the general trend for Cs was a release from the 235U peripheral agglomerates. The higher Cs measurement in the 235U-rich agglomerates close to the radial cracks results from both this release and the deposition of the Cs released from the hot central part.This singular release of Xe from the HBS bubbles of the 235U-rich agglomerates on the fuel periphery is all the more surprising that the Pu-rich agglomerates of the MIMAS MOX fuel irradiated under the same conditions [15] retained their fission gases in these areas. We found no definitive reason for that difference. the fission product implantation level has an effect. the local Pu content has also an effect. the actual local burn-up has an effect. This effect may be linked to fission through the local depletion of the fissile isotopes which changes the local chemical composition, as well as to the higher energy deposited there by electronic interactions at the beginning of the fission fragment recoils when compared with implanted areas with a low actual burn-up. Moreover, the major release of fission gases from the peripheral 235U-rich agglomerate HBS bubbles was evidenced in this heterogeneous UO2 fuel.The radial movement of Cs from the central part of the pellet towards its periphery was shown. This involved a deposition at the grain boundaries, including the HBS ones, around the radial cracks in the periphery. This showed the intergranular paths existing for the release of fission gases and Cs all through the fuel periphery. Grain Equivalent Circular Diameter (ECD) for which half of the surface is made of smaller grains and half of larger grains

Development and in vitro evaluation of potential electromodulated transdermal drug delivery systems based on carbon nanotube buckypapers.

PubMed

Schwengber, Alex; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L

2017-07-01

Buckypapers based on different types of carbon nanotubes with and without the addition of four model drugs, two of basic nature (clonidine hydrochloride, selegiline hydrochloride) and the others of acidic character (flurbiprofen, ketorolac tromethamine) were prepared and characterized. The influence of the conditions employed in the preparation of the buckypapers (dispersion time and solvents used in the preparation, as well as the type of carbon nanotubes used and the characteristics of the drug involved) on their conductivity was especially examined. The in vitro performance of the drug loaded buckypapers as passive and active transdermal drug release systems, the latter being modulated by means of the application of electric voltages, was studied. Passive drug loaded buckypapers presented characteristic release profiles, also depending on the drug used, which indicate differences in the drug-carbon nanotubes non-covalent interactions. Application of electrical biases of appropriate polarities enabled the modulation of the drug release profiles in any desired direction. Different mathematical models were fitted to passive and electromodulated experimental release data for the four model drugs. Among these models, the most appropriate for data description was a two-compartment pseudo-second-order one. Copyright © 2017 Elsevier B.V. All rights reserved.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

PubMed

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

Shock, release and Taylor impact of the semicrystalline thermoplastic polytetrafluoroethylene

NASA Astrophysics Data System (ADS)

Bourne, N. K.; Brown, E. N.; Millett, J. C. F.; Gray, G. T.

2008-04-01

The high strain-rate response of polymers is a subject that has gathered interest over recent years due to their increasing engineering importance, particularly in load bearing applications subject to extremes of pressure and strain rate. The current work presents two specific sets of experiments interrogating the effect of dynamic, high-pressure loading in the regime of the phase II to phase III pressure-induced crystalline phase transition in polytetrafluoroethylene (PTFE). These are gas-gun driven plate- and Taylor impact. Together these experiments highlight several effects associated with the dynamic, pressure-induced phase transitions in PTFE. An elevated release wave speed shows evidence of a pressure-induced phase change at a stress commensurate with that observed statically. It is shown that convergence between analytic derivations of release wave speed and the data requires the phase II to III transition to occur. Taylor impact is an integrated test that highlights continuum behavior that has origin in mesoscale response. There is a rapid transition from ductile to brittle behavior observed that occurs at a pressure consistent with this phase transition.

A nanoparticulate drug-delivery system for rivastigmine: physico-chemical and in vitro biological characterization.

PubMed

Craparo, Emanuela Fabiola; Pitarresi, Giovanna; Bondì, Maria Luisa; Casaletto, Maria Pia; Licciardi, Mariano; Giammona, Gaetano

2008-03-10

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG(2000) as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG(2000) copolymer mixture as the internal phase and triacetin saturated with water as the external phase, and characterized by dimensional analysis, zeta-potential measurements and XPS. in vitro biological tests demonstrated their cell compatibility and their ability to escape from phagocytosis. Rivastigmine was encapsulated into the nanoparticle structure and drug-release profiles from loaded samples were investigated in PBS at pH = 7.4 and human plasma.

Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

PubMed

Yanfei, Miao; Guoguang, Chen; Lili, Ren; Pingkai, Ouyang

2017-03-01

The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged T max and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

Nanoscale surface characterization and miscibility study of a spray-dried injectable polymeric matrix consisting of poly(lactic-co-glycolic acid) and polyvinylpyrrolidone.

PubMed

Meeus, Joke; Chen, Xinyong; Scurr, David J; Ciarnelli, Valeria; Amssoms, Katie; Roberts, Clive J; Davies, Martyn C; van Den Mooter, Guy

2012-09-01

Injectable controlled-release formulations are of increasing interest for the treatment of chronic diseases. This study aims to develop and characterize a polymeric matrix for intramuscular or subcutaneous injection, consisting of two biocompatible polymers, particularly suitable for formulating poorly soluble drugs. For this matrix, the water-insoluble polymer poly(lactic-co-glycolic acid) (PLGA) is combined with the water-soluble polymer polyvinylpyrrolidone (PVP). Microparticles of these two polymers were prepared by spray drying. The phase behavior of the samples was studied by means of modulated differential scanning calorimetry and the results showed that phase separation occurred in the bulk sample through evidence of two mixed amorphous phases, namely, a PLGA-rich phase and a PVP-rich phase. Characterization of the samples by scanning electron microscopy demonstrated that the spray-dried particles were hollow with a thin shell. Because of the importance in relation to stability and drug release, information about the surface of the microparticles was collected by different complementary surface analysis techniques. Atomic force microscopy gathered information about the morphology and phase behavior of the microparticle surface. Time-of-flight secondary ion mass spectrometry analysis of the particles revealed that the surface consisted mainly of the PLGA-rich phase. This was confirmed by X-ray photoelectron spectroscopy at an increased sampling depth (≈ 10 nm). Nanothermal analysis proved to be an innovative way to thermally detect the presence of the PLGA-dominated surface layer and the underlying PVP phase. Taken together, this information provides a rational basis for predicting the likely drug release behavior this formulation will display. Copyright © 2012 Wiley Periodicals, Inc.

Temperature control in a 30 stage, 5-cm Centrifugal Contactor Pilot Plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jack D. Law; Troy G. Garn; David H. Meikrantz

2009-09-01

Temperature profile testing was performed using a 30 stage 5-cm centrifugal contactor pilot plant. These tests were performed to evaluate the ability to control process temperature by adjusting feed solution temperatures. This would eliminate the need for complex jacketed heat exchanger installation on the centrifugal contactors. Thermocouples were installed on the inlet and outlets of each stage, as well as directly in the mixing zone of several of the contactor stages. Lamp oil, a commercially available alkane mixture of C14 to C18 chains, and tap water adjusted to pH 2 with nitric acid were the solution feeds for the temperaturemore » profile testing. Temperature data profiles for an array of total throughputs and contactor rpm values for both single-phase and two-phase systems were collected with selected profiles. The total throughput ranged from 0.5-1.4 L/min with rotor speeds from 3500-4000 rpm. Inlet solution temperatures ranging from ambient up to 50 °C were tested. Results of the two-phase temperature profile testing are detailed« less

The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae).

PubMed

Nogueira, Selene S C; Abreu, Shauana A; Peregrino, Helderes; Nogueira-Filho, Sérgio L G

2014-01-01

Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari), a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3) and unpredictable feeding phases (U1- signaled and U2- non-signaled). The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2) than during the other two predictable phases (C1 and C3). The peccaries also spent less time feeding during the signaled unpredictable phase (U1) and the following control phase (C2) than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2), also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

Trypanosoma cruzi: sequence of phagocytosis and cytotoxicity by human polymorphonuclear leucocytes.

PubMed Central

Rimoldi, M T; Cardoni, R L; Olabuenaga, S E; de Bracco, M M

1981-01-01

We have studied the relationship between phagocytosis and cytotoxicity of human polymorphonuclear leucocytes (PMN) to sensitized Trypanosoma cruzi. Assays were done simultaneously using [3H]-uridine labelled epimastigotes as target cells. Phagocytosis was evaluated by the uptake and cytotoxicity by the release of parasite associated [3H]-uridine. Both reactions reached maximum levels at the same effector- to target-cell ratio and antibody concentration. Uptake of epimastigotes by PMN was highest at 30 min and intracellular disruption and release of parasite debris took place later. In conditions that precluded repeated uptake of sensitized radiolabelled T. cruzi, the release profile of [3H]-uridine from PMN that contained intracellular parasites was similar to that of the standard cytotoxic assay. However, as the ingestion phase was separated from the release step, no lag in the onset of the reaction was observed. Although we cannot rule out extracellular killing, the results of this study demonstrate that the bulk of damaged T. cruzi epimastigotes had been previously internalized by the PMN. PMID:7016743

The physicochemical characterization and in vitro/in vivo evaluation of natural surfactants-based emulsions as vehicles for diclofenac diethylamine.

PubMed

Vucinić-Milanković, Nada; Savić, Snezana; Vuleta, Gordana; Vucinić, Slavica

2007-03-01

Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan stearate & sucrose cocoate, known as potential promoters of lamellar liquid crystals/gel phases, were investigated in order to formulate an optimal vehicle for amphiphilic drug - diclofenac diethylamine (DDA). Physico-chemical characterization and study of vehicle's physical stability were performed. Then, the in vitro DDA liberation profile, dependent on the mode of drug incorporation to the system, and the in vivo, short-term effects of chosen samples on skin parameters were examined. Droplets size distribution and rheological behavior indicated satisfying physical stability of both types of vehicles. Unexpectedly, the manner of DDA incorporation to the system had no significant influence on DDA release. In vivo study pointed to emulsion's favorable potential for skin hydration and barrier improvement, particularly in cetearyl glycoside-based vehicle.

Structure of the ripple phase in lecithin bilayers.

PubMed Central

Sun, W J; Tristram-Nagle, S; Suter, R M; Nagle, J F

1996-01-01

The phases of the x-ray form factors are derived for the ripple (Pbeta') thermodynamic phase in the lecithin bilayer system. By combining these phases with experimental intensity data, the electron density map of the ripple phase of dimyristoyl-phosphatidylcholine is constructed. The phases are derived by fitting the intensity data to two-dimensional electron density models, which are created by convolving an asymmetric triangular ripple profile with a transbilayer electron density profile. The robustness of the model method is indicated by the result that many different models of the transbilayer profile yield essentially the same phases, except for the weaker, purely ripple (0,k) peaks. Even with this residual ambiguity, the ripple profile is well determined, resulting in 19 angstroms for the ripple amplitude and 10 degrees and 26 degrees for the slopes of the major and the minor sides, respectively. Estimates for the bilayer head-head spacings show that the major side of the ripple is consistent with gel-like structure, and the minor side appears to be thinner with lower electron density. Images Fig. 1 Fig. 2 PMID:8692934

Acetate injection into anaerobic settled sludge for biological P-removal in an intermittently aerated reactor.

PubMed

Ahn, K H; Yoo, H; Lee, J W; Maeng, S K; Park, K Y; Song, K G

2001-01-01

Injecting acetate into the sludge layer during the settling and decanting periods was adopted to enhance phosphorus release inside the sludge layer during those periods and phosphorus uptake during the subsequent aeration period in a KIST Intermittently Decanted Extended Aeration (KIDEA) process. The relationship among nitrification, denitrification and phosphorus removal was investigated in detail and analyzed with a qualitative floc model. Dependencies of nitrification on the maximum DO level during the aerobic phase and phosphorus release on residual nitrate concentration during the settling phase were significant. High degree of nitrification resulted that phosphorus release inside the sludge layer was significantly interfered with nitrate due to the limitation of available acetate and the carbon sources from influent. Such limitation was related to the primary utilization of organic substance for denitrification in the outer layer of the floc and the retarded mass transfer into the inner layer of the floc. Nevertheless, effects of acetate injection on both denitrification and phosphorus release during the settling phase were significant. Denitrification rate after acetate injection was two times as high as that before acetate injection, and phosphorus release reached about 14 mg PO4(3-)-P/g MLVSS/hr during the decanting phase after the termination of denitrification inside the sludge layer. Extremely low level of maximum DO (around 0.5 mg/L) during the aerobic phase may inhibited nitrification, considerably, and thus nearly no nitrate was present. However, the absence of nitrate increased when the phosphorus release rate was reached up to 33 mg PO4(3-)-P/g MLVSS/hr during the settling and decanting phase, and nearly all phosphorus was taken up during subsequent aerobic phase. Since the sludge layer could function as a blocking layer, phosphorus concentrations in the supernatant was not influenced by the released phosphorus inside the sludge layer during the settling and decanting period. Phosphorus removal was directly (for uptake) and indirectly (for release) dependent on the median and maximum DO concentration during the aerobic phase, and those optimal values may exist within the range from 0.2 to 0.6 mg/L and 0.4 to 1.2 mg/L, respectively.

Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

NASA Astrophysics Data System (ADS)

Wang, YUAN; Hejuan, LIANG; Ping, HUANG; Xiaoqiang, AN; Jian, JIANG; Lili, CUI

2018-05-01

In the present study, the electret 5-fluorouracil patch was developed, the effective surface potential, piezoelectric coefficient d 33, open-circuit thermally stimulated discharge (TSD) current spectra and shear adhesion of the patch were measured. The drug release profile of the patch was determined by using high performance liquid chromatography method. A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch. The measurements of d 33 coefficient, TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules, change the distribution and interaction of the drug molecules in patch, therefore to increase the release of drug from the transdermal patch.

Profiles of polycyclic aromatic hydrocarbons and polychlorinated biphenyls from the combustion of biomass pellets.

PubMed

Atkins, A; Bignal, K L; Zhou, J L; Cazier, F

2010-03-01

An investigation was made into the emissions of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) as well as inorganic gases (e.g. CO) from a wood fired combustion boiler using wood pellets, under two different boiler operating modes. Levels of total PAHs varied from 6.4 and 154 microg m(-3), and were found to be dominating in the gas phase (>80%), regardless of pellet type and boiler operating mode. In addition to this, PAH concentrations were higher in slumber mode than in full flame, and increased with the moisture content of pellets, consistent with the lower combustion efficiency in slumber mode (58.6-64.3%) than in full flame (74.4-82.3%). PAHs in the gas phase comprised mainly of low molecular mass compounds, while PAHs in the particulate phase were mostly composed of high molecular mass compounds, consistent with the physicochemical properties of such compounds. In comparison to PAHs, significantly lower concentrations of PCBs (a maximum of 2.5 microg m(-3)) were released from pellet combustion, consistent with the virgin nature of the pellets. The PCBs in both the gas and particulate phases were dominated by hexachlorinated congeners, although congeners with more chlorine substitution were more abundant in the particulate phase than in gas phase. Significant relationships were established between CO and organic pollutants, and between PAHs and PCBs, which are useful tools for prediction purposes. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep.

PubMed

Luginbuehl, Vera; Zoidis, Evangelos; Meinel, Lorenz; von Rechenberg, Brigitte; Gander, Bruno; Merkle, Hans P

2013-09-01

Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization and release profile of (Mn, Al)-bearing deposits in drinking water distribution systems.

PubMed

Li, Guiwei; Ding, Yuanxun; Xu, Hongfu; Jin, Junwei; Shi, Baoyou

2018-04-01

Inorganic contaminants accumulation in drinking water distribution systems (DWDS) is a great threat to water quality and safety. This work assessed the main risk factors for different water pipes and discovered the release profile of accumulated materials in a full scale distribution system frequently suffered from water discoloration problem. Physicochemical characterization of pipe deposits were performed using X-ray fluorescence, scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The metal release profile was obtained through continuous monitoring of a full-scale DWDS area. The results showed that aluminum and manganese were the main metals of deposits in nonmetallic pipes, while iron was dominant in iron-based pipe corrosion scales. Manganese primarily existed as MnO 2 without well crystalline form. The relative abundance of Mn and Fe in deposits changed with their distance from the water treatment plant. Compared with iron in corrosion scales, Mn and Al were more labile to be released back into bulk water during unidirectional flushing process. A main finding of this work is the co-release behavior of Mn and Al in particulate form and significant correlation exists between these two metals. Dual control of manganese and aluminum in treated water is proposed to be essential to cope with discoloration and trace metal contamination in DWDS. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of sticky traps for adult Aedes mosquitoes in Malaysia: a potential monitoring and surveillance tool for the efficacy of control strategies.

PubMed

Roslan, Muhammad Aidil; Ngui, Romano; Vythilingam, Indra; Sulaiman, Wan Yusoff Wan

2017-12-01

The present study compared the performance of sticky traps in order to identify the most effective and practical trap for capturing Aedes aegypti and Aedes albopictus mosquitoes. Three phases were conducted in the study, with Phase 1 evaluating the five prototypes (Models A, B, C, D, and E) of sticky trap release-and-recapture using two groups of mosquito release numbers (five and 50) that were released in each replicate. Similarly, Phase 2 compared the performance between Model E and the classical ovitrap that had been modified (sticky ovitrap), using five and 50 mosquito release numbers. Further assessment of both traps was carried out in Phase 3, in which both traps were installed in nine sampling grids. Results from Phase 1 showed that Model E was the trap that recaptured higher numbers of mosquitoes when compared to Models A, B, C, and D. Further assessment between Model E and the modified sticky ovitrap (known as Model F) found that Model F outperformed Model E in both Phases 2 and 3. Thus, Model F was selected as the most effective and practical sticky trap, which could serve as an alternative tool for monitoring and controlling dengue vectors in Malaysia. © 2017 The Society for Vector Ecology.

Tension responses to rapid pressure release in glycerinated rabbit muscle fibers.

PubMed Central

Fortune, N S; Geeves, M A; Ranatunga, K W

1991-01-01

We have previously shown that the isometric tension of a fully calcium-activated skinned rabbit psoas muscle fiber is reversibly depressed by increased hydrostatic pressure. We report here the characterization of tension transients induced by a rapid (less than 1-ms) release of increased pressure at 12 degrees C. The tension transient consists of three clear phases, an initial further decrease of tension in phase with pressure change followed by two phases of tension increase back to the level recorded at ambient pressure. The mean reciprocal relaxation time for phase 2 (1/tau 2) was approximately 17 s-1 and that for phase 3 (1/tau 3) was 3 s-1. The presence of 20 mM inorganic phosphate markedly increased 1/tau 2 to approximately 52 s-1 and decreased 1/tau 3 to approximately 1.7 s-1. These observations are interpreted in terms of a pressure-sensitive transition between two attached crossbridge states of low (or zero) and higher force. This is compatible with the pressure-sensitive isomerization of actomyosin previously observed in solution. The results presented allow us to propose a coupling between a specific pressure-sensitive isomerization of purified actomyosin, the phosphate release step of the ATPase pathway, and the force-generating event of the cross-bridge cycle. PMID:1871140

Dynamics and Thermochemistry of Oxygen Uptake by a Mixed Ce-Pr Oxide

NASA Astrophysics Data System (ADS)

Sinev, M. Yu.; Fattakhova, Z. T.; Bychkov, V. Yu.; Lomonosov, V. I.; Gordienko, Yu. A.

2018-03-01

The dynamics of oxygen uptake by mixed Ce0.55Pr0.45O2-x oxide is studied in a pulsed oxygen supply mode using in situ high-temperature heat flow differential scanning calorimetry. It is stated that the oxidation proceeds in two regimes: a fast one at the beginning of the oxidation process, and a slow one, which is controlled by the diffusion of oxygen through the bulk of the solid at the later stages of the process. Analysis of the shape of calorimetric profiles reveals some processes, accompanied by heat release, that occur in the sample in the absence of oxygen in the gas phase. These could be due to both the redistribution of consumed oxygen in the oxide lattice and the lattice relaxation associated with the transformation of phases with different arrangements of oxygen vacancies in them. The heat effect (which diminishes from 60 to 40 kJ/mol in the course of oxygen uptake) associated with the oxidation of the reduced form of mixed Ce-Pr oxide, corresponds to the oxidation of praseodymium ions from (3+) to (4+).

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Tailoring sub-micron PLGA particle release profiles via centrifugal fractioning

PubMed Central

Dutta, Dipankar; Salifu, Mariama; Sirianni, Rachael W.; Stabenfeldt, Sarah E.

2016-01-01

Poly(D,L-lactic-co-glycolic) acid (PLGA)-based submicron particles are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA micro/nanoparticles typically requires optimization of the multi-parameter formulation, where small changes may cause drastic shifts in the resulting release profiles. In this study, we aimed to establish whether refining the average diameter of submicron particle populations after formulation alters protein release profiles. PLGA particles were first produced via double emulsion-solvent evaporation method to encapsulate bovine serum albumin. Particles were then subjected to centrifugal fractioning protocols varying in both spin time and force to determine encapsulation efficiency and release profile of differently sized populations that originated from a single batch. We found the average particle diameter was related to marked alterations in encapsulation efficiencies (range: 36.4–49.4%), burst release (range: 15.8–49.1%), and time for total cargo release (range: 38–78 days). Our data corroborate previous reports relating PLGA particle size with such release characteristics, however, this is the first study, to our knowledge, to directly compare particle population size while holding all formulation parameters constant. In summary, centrifugal fractioning to selectively control the population distribution of sub-micron PLGA particles represents a feasible tool to tailor release characteristics. PMID:26517011

Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.

PubMed

Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

2013-01-01

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties.

Closed System Step Etching of CI chondrite Ivuna reveals primordial noble gases in the HF-solubles

NASA Astrophysics Data System (ADS)

Riebe, My E. I.; Busemann, Henner; Wieler, Rainer; Maden, Colin

2017-05-01

We analyzed all the noble gases in HF-soluble phases in the CI chondrite Ivuna by in-vacuum gas release using the "Closed System Step Etching" (CSSE) technique, which allows for direct noble gas measurements of acid-soluble phases. The main motivation was to investigate if there are primordial noble gases in HF-soluble phases in Ivuna, something that has not been done before in CI chondrites, as most primordial noble gases are known to reside in HF-resistant phases. The first steps under mild etching released He, Ne, and Ar with solar-like elemental and isotopic compositions, confirming that Ivuna contains implanted solar wind (SW) noble gases acquired in the parent body regolith. The SW component released in some etch steps was elementally unfractionated. This is unusual as trapped SW noble gases are elementally fractionated in most meteoritic material. In the intermediate etch steps under slightly harsher etching, cosmogenic noble gases were more prominent than SW noble gases. The HF-soluble portion of Ivuna contained primordial Ne and Xe, that was most visible in the last etch steps after all cosmogenic and most SW gases had been released. The primordial Ne and Xe in the HF-solubles have isotopic and elemental ratios readily explained as a mixture of the two most abundant primordial noble gas components in Ivuna bulk samples: HL and Q. Only small fractions of the total HL and Q in Ivuna were released during CSSE analysis; ∼3% of 20NeHL and ∼4% of 132XeQ. HL is known to reside in nanodiamond-rich separates and Q-gases are most likely carried by a carbonaceous phase known as phase Q. Q-gases were likely released from an HF-soluble portion of phase Q. However, nanodiamonds might not be the source of the HL-gases released upon etching, since nanodiamond-rich separates are very HF-resistant and the less tightly bound nanodiamond component P3 was not detected.

Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

NASA Astrophysics Data System (ADS)

Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Vittorio, Orazio; Puoci, Francesco; Picci, Nevio; Iemma, Francesca

2013-04-01

Native gelatin, N, N'-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

The influence of the energy emitted by solar flare soft X-ray bursts on the propagation of their associated interplanetary shock waves

NASA Technical Reports Server (NTRS)

Pinter, S.; Dryer, M.

1985-01-01

The relationship between the thermal energy released from 29 solar flares and the propagation features of their associated interplanetary shock waves that were detected at 1 AU is investigated. The 29 interplanetary shock waves were identified unambiguously and their tracking from each solar flare was deduced by tracking their associated interplanetary type-II radio emission. The thermal energy released in the solar flares was estimated from the time-intensity profiles of 1-8 A soft X-ray bursts from each flare. A good relationship is found between the flares' thermal energy with the IP shock-waves' transient velocity and arrival time at the earth - that is, the largest flare energy released is associated with the faster shock waves. Finally, a possible scenario of formation of a shock wave during the early phase of the flare and its propagation features is discussed.

Sulfation of K-based Lean NOx Trap while Cycling Between Lean and Rich Conditions: I. Microreactor Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toops, Todd J; Pihl, Josh A

2008-01-01

Exposure of Pt/K/Al{sub 2}O{sub 3} to 15 ppm SO{sub 2} reduces the NOx activity at 200, 300, and 400 C at significantly different rates--1.5, 8.5, and 18.0 {micro}mol NOx/(h g{sub cat}), respectively. During the initial sulfation, NOx conversion is directly linked to lean phase storage capacity, and sulfation does not impact the reduction kinetics since the amount of unconverted NOx was constant or decreased with increasing sulfation time. A portion of sulfur stored at 200 C desorbs upon mild heating to 400 C while cycling between lean and rich conditions. This apparently is a result of sulfur being released frommore » Al{sub 2}O{sub 3}; however, performance is not significantly recovered as much of the sulfur is re-adsorbed on the K-phase. This is apparent from analysis of the NOx storage and release profiles. Additional analysis of these profiles suggests that SO{sub 2} initially adsorbs near Pt before interacting with other sites further away from Pt at 300 C. At 400 C, it appears that SO{sub 2} either preferentially adsorbs near Pt and then quickly diffuses along the surface to other less proximal sites, or it directly adsorbs on sites further away from Pt. De-sulfurization up to 800 C using a temperature programmed reduction (TPR) procedure and rich conditions with both CO{sub 2} and H{sub 2}O restored 73=94% of the LNT performance at 300 and 400 C. However, the recovered performance measured at 200 C was only 34-49% of the original NOx reduction activity. H{sub 2}S and SO{sub 2} were the primary de-sulfurization products with H{sub 2}S having a maximum release between 690 and 755 C, while SO{sub 2} had a peak release between 770 and 785 C. The sulfation temperature does not have a significant impact on the recovered performance, the de-sulfurization products or the sulfur release temperature.« less

Additively Manufactured and Surface Biofunctionalized Porous Nitinol.

PubMed

Gorgin Karaji, Z; Speirs, M; Dadbakhsh, S; Kruth, J-P; Weinans, H; Zadpoor, A A; Amin Yavari, S

2017-01-18

Enhanced bone tissue regeneration and improved osseointegration are among the most important goals in design of multifunctional orthopedic biomaterials. In this study, we used additive manufacturing (selective laser melting) to develop multifunctional porous nitinol that combines superelasticity with a rationally designed microarchitecture and biofunctionalized surface. The rational design based on triply periodic minimal surfaces aimed to properly adjust the pore size, increase the surface area (thereby amplifying the effects of surface biofunctionalization), and resemble the curvature characteristics of trabecular bone. The surface of additively manufactured (AM) porous nitinol was biofunctionalized using polydopamine-immobilized rhBMP2 for better control of the release kinetics. The actual morphological properties of porous nitinol measured by microcomputed tomography (e.g., open/close porosity, and surface area) closely matched the design values. The superelasticity originated from the austenite phase formed in the nitinol porous structure at room temperature. Polydopamine and rhBMP2 signature peaks were confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy tests. The release of rhBMP2 continued until 28 days. The early time and long-term release profiles were found to be adjustable independent of each other. In vitro cell culture showed improved cell attachment, cell proliferation, cell morphology (spreading, spindle-like shape), and cell coverage as well as elevated levels of ALP activity and increased calcium content for biofunctionalized surfaces as compared to as-manufactured specimens. The demonstrated functionalities of porous nitinol could be used as a basis for deployable orthopedic implants with rationally designed microarchitectures that maximize bone tissue regeneration performance by release of biomolecules with adjustable and well-controlled release profiles.

Chemistry in the Dusty Coma of Comet Hale-Bopp

NASA Astrophysics Data System (ADS)

Boice, D. C.; Cochran, A. L.; Disanti, M. A.; Huebner, W. F.

1998-09-01

Recent progress on a multifluid, hydrodynamic model is presented for the dusty gas flow in the inner coma of comet Hale-Bopp at several heliocentric distances. The simulations are based on a 1-D neutral coma model with detailed photo and gas-phase chemistry and dust entrainment by the gas, a separate energy balance for the electrons, separate flow of the neutral gas, fast neutral atomic and molecular hydrogen, and dust entrainment with fragmentation. The model accounts for three sources of gas release: sublimation from surface ices, transport of gas from subsurface regions through the surface, and release of gas from dust in the coma. This permits a consistent study of the importance and strength of each possible source for a variety of gas-phase species. The simulations allow a study of the changes with heliocentric distance of features within a cometary coma, e.g., spatial distributions of gas-phase species and dust of various sizes and the velocity and temperature profiles. In particular, the model is used to probe spatial distributions of gas-phase species (e.g., CN, CH, C_3, C_2, HCN, HNC, CO) and dust, and the velocity and temperature structure to understand the complex gas-phase chemistry that occurs in the inner coma. Comparisons with observations are made where available to characterize the environment surrounding comet Hale-Bopp and to aid in assimilating a variety of diverse observations of this unique comet.

Oxychlorine and Chloride/Ferrian Saponite Mixtures as a Possible Source of Hydrochloric Acid Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater, Mars

NASA Astrophysics Data System (ADS)

Hogancamp, J. V.; Sutter, B.; Archer, D., Jr.; Ming, D. W.; Mahaffy, P. R.

2017-12-01

The Sample Analysis at Mars (SAM) instrument on board the Curiosity Rover has detected HCl gas releases from several analyzed Gale Crater sediments, which are attributed to the presence of perchlorates, chlorates, and/or chlorides in martian sediment. Previous SAM analog laboratory analyses found that most pure perchlorates and chlorates produced HCl at different temperatures than those observed in the SAM data. Subsequent studies examined the effects of perchlorate and chlorate mixtures with Gale Crater analog iron phases, which are known to catalyze oxychlorine decomposition. Several mixtures produced characteristic O2 releases at similar temperatures as Gale Crater materials, but most of these mixtures did not produce HCl releases comparable to those detected by the SAM instrument. Perchlorates, chlorates, and chlorides were mixed with Gale Crater analog ferrian saponite to understand evolved HCl detected by SAM. Evolved water from thermally decomposing saponite is hypothesized to react with residual chloride phases from oxychlorine decomposition to produce high temperature (>700°C) HCl. Mixtures of chlorates, perchlorates, or chlorides with ferrian saponite were heated to 1000 °C in a laboratory analog SAM instrument. Results demonstrated that all chlorate and perchlorate mixtures produce HCl releases below 1000 °C when mixed with ferrian saponite. Mixtures of chlorides with ferrian saponite produced no oxygen releases but did produce HCl releases with peaks below 1000 °C. Ferrian saponite/Mg-chlorate mixtures produced two HCl releases (347 and 820 °C) similar to the Cumberland drilled sample. Additionally, sodium chloride mixed with ferrian saponite produced no oxygen releases and an HCl release (767 °C) similar to the Quela drilled sample. The Marimba drilled sample, which also produced no oxychlorine-derived oxygen, produced a high temperature HCl release that may be the result of chloride(s) reacting with evolved water from thermally decomposing ferrian saponite. Results of this work demonstrated that chlorides in the presence of evolved water from thermally decomposing saponite can explain the high temperature evolved HCl detected by SAM. Chlorides may either be native to the sample or be produced by perchlorate/chlorate thermal decomposition in order to yield Cl for high temperature (>700 °C) HCl production. Mg bearing Cl phases tend to produce two HCl releases (347-496 and 820 °C) while Ca and Na bearing phases produced one high temperature (>700 °C) HCl release. HCl release temperatures can be used to indicate the cation-type of the oxychlorine phase or chloride which is critical to understanding past geochemical conditions in Gale Crater.

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

PubMed Central

Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

2012-01-01

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Fuel spill identification using solid-phase extraction and solid-phase microextraction. 1. Aviation turbine fuels.

PubMed

Lavine, B K; Brzozowski, D M; Ritter, J; Moores, A J; Mayfield, H T

2001-12-01

The water-soluble fraction of aviation jet fuels is examined using solid-phase extraction and solid-phase microextraction. Gas chromatographic profiles of solid-phase extracts and solid-phase microextracts of the water-soluble fraction of kerosene- and nonkerosene-based jet fuels reveal that each jet fuel possesses a unique profile. Pattern recognition analysis reveals fingerprint patterns within the data characteristic of fuel type. By using a novel genetic algorithm (GA) that emulates human pattern recognition through machine learning, it is possible to identify features characteristic of the chromatographic profile of each fuel class. The pattern recognition GA identifies a set of features that optimize the separation of the fuel classes in a plot of the two largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected features is primarily about the differences between the fuel classes.

Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

DOE PAGES

Saha, Dipendu; Moken, Tara; Chen, Jihua; ...

2015-02-24

Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m 2 g –1 and pore volume 0.63–1.03 cm 3 g –1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies onmore » human cells with similar materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.« less

Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saha, Dipendu; Moken, Tara; Chen, Jihua

Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m 2 g –1 and pore volume 0.63–1.03 cm 3 g –1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies onmore » human cells with similar materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.« less

Drug release from slabs and the effects of surface roughness.

PubMed

Kalosakas, George; Martini, Dimitra

2015-12-30

We discuss diffusion-controlled drug release from slabs or thin films. Analytical and numerical results are presented for slabs with flat surfaces, having a uniform thickness. Then, considering slabs with rough surfaces, the influence of a non-uniform slab thickness on release kinetics is numerically investigated. The numerical release profiles are obtained using Monte Carlo simulations. Release kinetics is quantified through the stretched exponential (or Weibull) function and the resulting dependence of the two parameters of this function on the thickness of the slab, for flat surfaces, and the amplitude of surface fluctuations (or the degree of thickness variability) in case of roughness. We find that a higher surface roughness leads to a faster drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles

PubMed Central

Zhang, Hong; Zhang, Fu-Ming; Yan, Shi-Jun

2012-01-01

Sorafenib solid lipid nanoparticles (S-SLN) were prepared by emulsion evaporation–solidification at low temperature. Morphology was examined by transmission electron microscope. Particle size and zeta potential were determined by laser granularity equipment. Encapsulation efficiency (EE) was detected by Sephadex gel chromatography and high-performance liquid chromatography (HPLC). The in vitro release profile of S-SLN was studied with dialysis technology. The lyophilized injection of S-SLN was prepared by freeze drying and analyzed by differential scanning calorimetry. The plasma concentration of sorafenib in blood was determined by HPLC. The solid lipid nanoparticles assumed a spherical shape with an even distribution of diameter and particle size 108.23 ± 7.01 nm (n = 3). The polydispersity index, zeta potential, and EE were determined to be 0.25 ± 0.02, −16.37 ± 0.65 mV, and 93.49% ± 1.87%, respectively (n = 3). The in vitro release accorded with the Weibull distribution model. An equal volume of 15% (w/v) mannitol performed better as the protective agent for a lyophilized injection of S-SLN with a new material phase formation. The pharmacokinetic processes of sorafenib solution and lyophilized injection of S-SLN in vivo were in accordance with the two-compartment and one-compartment models, respectively. S-SLN nanoparticles are thus considered a promising drug-delivery system. PMID:22787390

Direct comparison of two different mesalamine formulations for the maintenance of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Aida, Yoshiyuki; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools. Results: In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations. Conclusions: The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289). (Inflamm Bowel Dis 2010) PMID:20049949

Hg and Pt-metals in meteorite carbon-rich residues - Suggestions for possible host phase for Hg

NASA Technical Reports Server (NTRS)

Jovanovic, S.; Reed, G. W., Jr.

1980-01-01

Carbon-rich and oxide residual phases have been isolated from Allende and Murchison by acid demineralization for the determination of their Hg, Pt-metal, Cr, Sc, Co, and Fe contents. Experimental procedures used eliminated the possibility of exogenous and endogenous contaminant trace elements from coprecipitating with the residues. Large enrichments of Hg and Pt-metals were found in Allende but not in Murchison residues. Hg-release profiles from stepwise heating experiments suggest a sulfide as the host for Hg. Diffusion calculations for Hg based on these experiments indicate an activation energy of 7-8 kcal/mol, the same as that for Hg in troilite from an iron meteorite. This is further support for a sulfide host phase for Hg. Equilibration of Hg with this phase at approximately 900 K is indicated. Reasons for the presence of Pt-metals in noncosmic relative abundances are explored.

Density profiles around A+B→C reaction-diffusion fronts in partially miscible systems: A general classification.

PubMed

Loodts, V; Trevelyan, P M J; Rongy, L; De Wit, A

2016-10-01

Various spatial density profiles can develop in partially miscible stratifications when a phase A dissolves with a finite solubility into a host phase containing a dissolved reactant B. We investigate theoretically the impact of an A+B→C reaction on such density profiles in the host phase and classify them in a parameter space spanned by the ratios of relative contributions to density and diffusion coefficients of the chemical species. While the density profile is either monotonically increasing or decreasing in the nonreactive case, reactions combined with differential diffusivity can create eight different types of density profiles featuring up to two extrema in density, at the reaction front or below it. We use this framework to predict various possible hydrodynamic instability scenarios inducing buoyancy-driven convection around such reaction fronts when they propagate parallel to the gravity field.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

PubMed Central

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Background Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. Methods The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Results and Discussion Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. Conclusions This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms. PMID:27479702

Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

PubMed

Skripnik, K K S; Riekes, M K; Pezzini, B R; Cardoso, S G; Stulzer, H K

2017-07-01

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

Audiologist-patient communication profiles in hearing rehabilitation appointments.

PubMed

Meyer, Carly; Barr, Caitlin; Khan, Asaduzzaman; Hickson, Louise

2017-08-01

To profile the communication between audiologists and patients in initial appointments on a biomedical-psychosocial continuum; and explore the associations between these profiles and 1) characteristics of the appointment and 2) patients' decisions to pursue hearing aids. Sixty-three initial hearing assessment appointments were filmed and audiologist-patient communication was coded using the Roter Interaction Analysis System. A hierarchical cluster analysis was conducted to profile audiologist-patient communication, after which regression modelling and Chi-squared analyses were conducted. Two distinct audiologist-patient communication profiles were identified during both the history taking phase (46=biopsychosocial profile, 15=psychosocial profile) and diagnosis and management planning phase (45=expanded biomedical profile, 11=narrowly biomedical profile). Longer appointments were significantly more likely to be associated with an expanded biomedical interaction during the diagnosis and management planning phase. No significant associations were found between audiologist-patient communication profile and patients' decisions to pursue hearing aids. Initial audiology consultations appear to remain clinician-centred. Three quarters of appointments began with a biopsychosocial interaction; however, 80% ended with an expanded biomedical interaction. Findings suggest that audiologists could consider modifying their communication in initial appointments to more holistically address the needs of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlations in metal release profiles following sorption by Lemna minor.

PubMed

Üçüncü Tunca, Esra; Ölmez, Tolga T; Özkan, Alper D; Altındağ, Ahmet; Tunca, Evren; Tekinay, Turgay

2016-08-02

Following the rapid uptake of contaminants in the first few hours of exposure, plants typically attempt to cope with the toxic burden by releasing part of the sorbed material back into the environment. The present study investigates the general trends in the release profiles of different metal(loid)s in the aquatic macrophyte Lemna minor and details the correlations that exist between the release of metal(loid) species. Water samples with distinct contamination profiles were taken from Nilüfer River (Bursa, Turkey), Yeniçağa Lake (Bolu, Turkey), and Beyşehir Lake (Konya, Turkey) and used for release studies; 36 samples were tested in total. Accumulation and release profiles were monitored over five days for 11 metals and a metalloid ((208)Pb, (111)Cd, (52)Cr,(53)Cr,(60)Ni,(63)Cu,(65)Cu,(75)As,(55)Mn, (137)Ba, (27)Al, (57)Fe, (66)Zn,(68)Zn) and correlation, cluster and principal component analyses were employed to determine the factors that affect the release of these elements. Release profiles of the tested metal(loid)s were largely observed to be distinct; however, strong correlations have been observed between certain metal pairs (Cr/Ni, Cr/Cu, Zn/Ni) and principal component analysis was able to separate the metal(loid)s into three well-resolved groups based on their release.

Use of natural and biobased materials for controlled-release of urea in water: Environmental applications

USDA-ARS?s Scientific Manuscript database

Urea pearls were encapsulated in cloisite-based matrices using different natural materials (lignin, beeswax and latex) to control the release of urea over time. It was found that all cloisite-based fertilizer tablets showed better release profiles than neat urea tablets. The best release profile was...

Polarization-multiplexed plasmonic phase generation with distributed nanoslits.

PubMed

Lee, Seung-Yeol; Kim, Kyuho; Lee, Gun-Yeal; Lee, Byoungho

2015-06-15

Methods for multiplexing surface plasmon polaritons (SPPs) have been attracting much attention due to their potentials for plasmonic integrated systems, plasmonic holography, and optical tweezing. Here, using closely-distanced distributed nanoslits, we propose a method for generating polarization-multiplexed SPP phase profiles which can be applied for implementing general SPP phase distributions. Two independent types of SPP phase generation mechanisms - polarization-independent and polarization-reversible ones - are combined to generate fully arbitrary phase profiles for each optical handedness. As a simple verification of the proposed scheme, we experimentally demonstrate that the location of plasmonic focus can be arbitrary designed, and switched by the change of optical handedness.

Investigation of the Hazards Posed by Chemical Vapors Released in Marine Operations - Phase II.

DTIC Science & Technology

1983-04-01

Methodology 4 IV.1 Nondimensional Radial Velocity Profiles Following Jet Impingement 30 IV.2 3.66m Cube Ventilation Test Tank Apparatus 44 IV.3 Test No. 19...available for product evaporation in the bays immediately beneath the * blower jet . The second modification would reflect the fact that bays that are... jet impingement model in Reference 8 to generate an ex- pression for Uwind* The model in Reference 8 was derived for the normal impinge- ment of a

Coil-current effect in Kibble balances: analysis, measurement, and optimization

NASA Astrophysics Data System (ADS)

Li, S.; Bielsa, F.; Stock, M.; Kiss, A.; Fang, H.

2018-02-01

The Kibble balance is expected to become an important instrument in the near future for realizing the unit of mass, the kilogram, in the revised international system of units (SI). The Kibble balance assumes an equality of two magnetic profiles measured in the weighing and velocity phases. A recent study conducted in the Kibble balance group at the Bureau International des Poids et Mesures (BIPM) showed that the coil current could significantly affect the magnetic profile, which should be carefully taken into account in the Kibble balance experiment. This paper gives a deeper understanding and investigation of the effect, and discusses the magnetic profile change due to the coil current, for both the classical two-mode and the one-mode Kibble balances. The coil current effect has been theoretically and experimentally investigated based on a typical magnet design with an air gap. One important conclusion found in the one-mode Kibble balance is that the magnetic profile change measured in the velocity phase is twice the change in the weighing phase. A compensation suggestion, to minimize the profile change due to the coil current in a BIPM-type magnet, is presented.

Exploring the additivity of binaural and monaural masking release

PubMed Central

Hall, Joseph W.; Buss, Emily; Grose, John H.

2011-01-01

Experiment 1 examined comodulation masking release (CMR) for a 700-Hz tonal signal under conditions of NoSo (noise and signal interaurally in phase) and NoSπ (noise in phase, signal out of phase) stimulation. The baseline stimulus for CMR was either a single 24-Hz wide narrowband noise centered on the signal frequency [on-signal band (OSB)] or the OSB plus, a set of flanking noise bands having random envelopes. Masking noise was either gated or continuous. The CMR, defined with respect to either the OSB or the random noise baseline, was smaller for NoSπ than NoSo stimulation, particularly when the masker was continuous. Experiment 2 examined whether the same pattern of results would be obtained for a 2000-Hz signal frequency; the number of flanking bands was also manipulated (two versus eight). Results again showed smaller CMR for NoSπ than NoSo stimulation for both continuous and gated masking noise. The CMR was larger with eight than with two flanking bands, and this difference was greater for NoSo than NoSπ. The results of this study are compatible with serial mechanisms of binaural and monaural masking release, but they indicate that the combined masking release (binaural masking-level difference and CMR) falls short of being additive. PMID:21476663

The biomechanics of javelin throwing: a review.

PubMed

Bartlett, R M; Best, R J

1988-01-01

In this paper, the scientific literature and that on the sports sciences relevant to javelin throwing is critically reviewed. This is particularly timely because of the change in the specification of the javelin for the men's event, which was introduced by the IAAF in 1986. A full discussion of the aerodynamics of the javelin is presented with due consideration of the change in pitching moment characteristics that the rules change had brought about. The uses and limitations of current computer programs for simulating javelin flight, in order to estimate optimal release parameters, are profiled. Consideration is also given to the effects of wind velocity, air density, javelin weight and the flutter and spin of the javelin on its flight. The review further considers the optimization of release parameters, drawing upon computer simulations and field-based data. The effects of release speed, release height, release angle, release angle of attack and release pitch rate are assessed. The javelin throwing technique is discussed in relation to cinematographically derived data, including an evaluation of experimental procedures. The importance to successful performance of the grip, the run-up and transition phases, the cross over and delivery strides are each reviewed. Finally, some prognoses as to the direction of future research into this complex throwing skill are offered.

Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions.

PubMed

Djekic, Ljiljana; Primorac, Marija; Filipic, Slavica; Agbaba, Danica

2012-08-20

The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. The primary surfactant was PEG-8 caprylic/capric glycerides (Labrasol). The cosurfactants were commercially available mixtures of octoxynol-12 and polysorbate 20 without or with the addition of PEG-40 hydrogenated castor oil (Solubilisant gamma 2421 and Solubilisant gamma 2429, respectively). The oil phase of microemulsions was isopropyl myristate. Phase behaviour study of the pseudo-ternary systems Labrasol/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K(m)) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. Solubilization of a model drug ibuprofen in concentration common for topical application (5%, w/w) was achieved at the water contents below 50% (w/w). Drug free and ibuprofen-loaded microemulsions M1-M6, containing 45% (w/w) of water phase, were prepared and characterized by polarized light microscopy, conductivity, pH, rheological and droplet size measurements. In vitro ibuprofen release kinetics from the microemulsions was investigated using paddle-over-enhancer cell method and compared with the commercial 5% (w/w) ibuprofen hydrogel product (Deep Relief, Mentholatum Company Ltd., USA). The investigated microemulsions were isotropic, low viscous Bingham-type liquids with the pH value (4.70-6.61) suitable for topical application. The different efficiency of the tensides mixtures for microemulsion stabilisation was observed, depending on the cosurfactant type and K(m) value. Solubilisant gamma 2429 as well as higher K(m) (i.e., lower relative content of the cosurfactant) provided higher surfactant/cosurfactant synergism. The drug molecules were predominantly solubilized within the interface film. The amount of drug released from the formulations M3 (10.75%, w/w) and M6 (13.45%, w/w) (K(m) 60:40) was limited in comparison with the reference (22.22%, w/w) and follows the Higuchi model. Microemulsions M2 and M5 (K(m) 50:50) gave zero order drug release pattern and ∼15% (w/w) ibuprofen released. The release profiles from microemulsions M1 and M4 (K(m) 40:60) did not fit well with the models used for analysis, although the amounts of ibuprofen released (24.47%, w/w) and 17.99% (w/w), respectively) were comparable to that of the reference hydrogel. The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides corresponded to the faster drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

A comparative study on the effects of amphiphilic and hydrophilic polymers on the release profiles of a poorly water-soluble drug.

PubMed

Irwan, Anastasia W; Berania, Jacqueline E; Liu, Xueming

2016-03-01

This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.

Impedance probe to measure local void fraction profiles

NASA Astrophysics Data System (ADS)

Teyssedou, A.; Tapucu, A.; Lortie, M.

1988-04-01

A conductivity-type local void measurement system has been developed. The effects of the sensor tip geometry, the unbalance of the front-end bridge, the comparator threshold level, and the mass fluxes on the response of the instrument have been studied. The system has been calibrated under air-water two-phase flow conditions using the quick-closing-valve technique. Comparison of the void profiles obtained with the conductivity probe with those obtained using an optical probe confirms the applicability of this system for two-phase (air-water) flows.

Jeffamine derivatized TentaGel beads and poly(dimethylsiloxane) microbead cassettes for ultrahigh-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound combinatorial small molecule libraries.

PubMed

Townsend, Jared B; Shaheen, Farzana; Liu, Ruiwu; Lam, Kit S

2010-09-13

A method to efficiently immobilize and partition large quantities of microbeads in an array format in microfabricated poly(dimethylsiloxane) (PDMS) cassette for ultrahigh-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound (OBOC) combinatorial libraries is described. Commercially available Jeffamine triamine T-403 (∼440 Da) was derivatized such that two of its amino groups were protected by Fmoc and the remaining amino group capped with succinic anhydride to generate a carboxyl group. This resulting trifunctional hydrophilic polymer was then sequentially coupled two times to the outer layer of topologically segregated bilayer TentaGel (TG) beads with solid phase peptide synthesis chemistry resulting in beads with increased loading capacity, hydrophilicity, and porosity at the outer layer. We have found that such bead configuration can facilitate ultrahigh-throughput in situ releasable solution-phase screening of OBOC libraries. An encoded releasable OBOC small molecule library was constructed on Jeffamine derivatized TG beads with library compounds tethered to the outer layer via a disulfide linker and coding tags in the interior of the beads. Compound-beads could be efficiently loaded (5-10 min) into a 5 cm diameter Petri dish containing a 10,000-well PDMS microbead cassette, such that over 90% of the microwells were each filled with only one compound-bead. Jurkat T-lymphoid cancer cells suspended in Matrigel were then layered over the microbead cassette to immobilize the compound-beads. After 24 h of incubation at 37 °C, dithiothreitol was added to trigger the release of library compounds. Forty-eight hours later, MTT reporter assay was used to identify regions of reduced cell viability surrounding each positive bead. From a total of about 20,000 beads screened, 3 positive beads were detected and physically isolated for decoding. A strong consensus motif was identified for these three positive compounds. These compounds were resynthesized and found to be cytotoxic (IC(50) 50-150 μM) against two T-lymphoma cell lines and less so against the MDA-MB 231 breast cancer cell line. This novel ultrahigh-throughput OBOC releasable method can potentially be adapted to many existing 96- or 384-well solution-phase cell-based or biochemical assays.

Jeffamine Derivatized TentaGel Beads and PDMS Microbead Cassettes for Ultra-high Throughput in situ Releasable Solution-Phase Cell-based Screening of OBOC Combinatorial Small Molecule Libraries

PubMed Central

Townsend, Jared B.; Shaheen, Farzana; Liu, Ruiwu; Lam, Kit S.

2011-01-01

A method to efficiently immobilize and partition large quantities of microbeads in an array format in microfabricated polydimethylsiloxane (PDMS) cassette for high-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound (OBOC) combinatorial libraries is described. Commercially available Jeffamine triamine T-403 (∼440 Da) was derivatized such that two of its amino groups were protected by Fmoc and the remaining amino group capped with succinic anhydride to generate a carboxyl group. This resulting tri-functional hydrophilic polymer was then sequentially coupled two times to the outer layer of topologically segregated bilayer TentaGel (TG) beads with solid phase peptide synthesis chemistry, resulting in beads with increased loading capacity, hydrophilicity and porosity at the outer layer. We have found that such bead configuration can facilitate ultra high-throughput in situ releasable solution-phase screening of OBOC libraries. An encoded releasable OBOC small molecule library was constructed on Jeffamine derivatized TG beads with library compounds tethered to the outer layer via a disulfide linker and coding tags in the interior of the beads. Compound-beads could be efficiently loaded (5-10 minutes) into a 5 cm diameter Petri dish containing a 10,000-well PDMS microbead cassette, such that over 90% of the microwells were each filled with only one compound-bead. Jurkat T-lymphoid cancer cells suspended in Matrigel® were then layered over the microbead cassette to immobilize the compound-beads. After 24 hours of incubation at 37°C, dithiothreitol was added to trigger the release of library compounds. Forty-eight hours later, MTT reporter assay was used to identify regions of reduced cell viability surrounding each positive bead. From a total of about 20,000 beads screened, 3 positive beads were detected and physically isolated for decoding. A strong consensus motif was identified for these three positive compounds. These compounds were re-synthesized and found to be cytotoxic (IC50 50-150 μM) against two T-lymphoma cell lines and less so against the MDA-MB 231 breast cancer cell line. This novel ultra high-throughput OBOC releasable method can potentially be adapted to many existing 96- or 384-well solution-phase cell-based or biochemical assays. PMID:20593859

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery

PubMed Central

Khan, Zaheeda; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery. PMID:24024200

Spent fuel reaction - the behavior of the {epsilon}-phase over 3.1 years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finn, P.A.; Hoh, J.C.; Wolf, S.F.

The release fractions of the five elements in the {epsilon}-phase ({sup 99}Tc, {sup 97}Mo, Ru, Rh, and Pd) as well as that of {sup 238}U are reported for the reaction of two oxide fuels (ATM-103 and ATM-106) in unsaturated tests under oxidizing conditions. The {sup 99}Tc release fractions provide a lower limit for the magnitude of the spent fuel reaction. The {sup 99}Tc release fractions indicate that a surface reaction might be the rate controlling mechanism for fuel reaction under unsaturated conditions and the oxidant is possibly H{sub 2}O{sub 2}, a product of alpha radiolysis of water.

Preparation and evaluation of enteric coated tablets of hot melt extruded lansoprazole

PubMed Central

Alsulays, Bader B.; Kulkarni, Vijay; Alshehri, Sultan M.; Almutairy, Bjad K.; Ashour, Eman A.; Morott, Joseph T.; Alshetaili, Abdullah S.; Park, Jun-Bom; Tiwari, Roshan V.; Repka, Michael A.

2017-01-01

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L 100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L 100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for 6 months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods. PMID:27486807

Polymorphic transition of tin under shock wave compression: Experimental results

NASA Astrophysics Data System (ADS)

Chauvin, C.; Petit, J.; Sinatti, F.

2012-08-01

In this work, the β-bct polymorphic transition in tin is investigated by means of plate impact experiments. The Sn target surface is observed in a partially released state obtained thanks to a transparent lithium fluoride (LiF) anvil. We report both measurements of interface velocity and temperature obtained using Photon Doppler Velocimetry and IR optical pyrometer on shock-loaded tin from 8 to 16 GPa. We show that the Mabire Model EOS associated to the SCG plasticity model provides an overall good estimate of the velocity profiles. However, depnding on the shock amplitude, its prediction of the temperature profile may be less satisfactory, hence underlining the need for future improvements in terms of phase transition kinetics description.

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

USGS Publications Warehouse

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.; Knaeble, Alan R.; Marcus, Matthew A.; Lynch, Joshua K.; Toner, Brandy M.

2017-01-01

e of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (lXAS) approach is developed and applied to rotosonic drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s lXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity observed in the distribution of elevated-As wells.

Experimental Studies of Adhesion of a Highly Swollen Gel

NASA Astrophysics Data System (ADS)

Cole, Phillip; Emerson, John

2003-03-01

A fracture mechanics methodology based on the Johnson-Kendall-Roberts (JKR) theory is used to quantify the self-adhesion of a highly swollen gel. The solid phase of the gel is a cross-linked polybutadiene and the liquid phase is dibutylphthlate (maximum 60% by weight). In these experiments two nearly identical gel lenses are brought into contact. Bonding and separation of contact is analyzed in terms of the modified JKR theory of Shull [1]. Simultaneous measurements of the applied load, the load point displacement and the contact radius between the lenses allow us to determine the elastic modulus of the gel and the energy release rate. It also allows us to determine whether the observed hysteresis is primarily due to surface dissipation or due to bulk viscoelasticity. The energy release rate is found to be approximately constant during the bonding phase of the experiment. During the debonding phase, the energy release rate increases with the crack velocity or the receding rate of contact radius. Self-adhesion is quantified in the debonding phase through the relationship between the energy release rate and the crack growth rate. The energy release rate during the bonding phase is compared to the surface tension of the liquid and the solid. We also study the effect of liquid phase on the self-adhesion by varying the amount of liquid from zero percent to the maximum of sixty percent. [1] Shull, K. R. Materials Science and Engineering R-Reports, 36 (2002) 1-45. This work was performed at Sandia National Laboratories, supported by the United States Department of Energy under contract number DE-AC04-94AL85000.

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

PubMed

Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

2008-01-01

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

Histamine release, formation of prostaglandin-like activity (SRS-C) and mast cell degranulation by the direct lytic factor (DLF) and phospholipase A of cobra venom.

PubMed

Damerau, B; Lege, L; Oldigs, H D; Vogt, W

1975-01-01

Cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guine-pig lungs than in rat peritoneal cell suspensions. 2. Phase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and phase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

PubMed

Lin, Shan-Yang; Li, Mei-Jane; Lin, Kung-Hsu

2004-08-16

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

Return glider radiosonde to measure temperature, humidity and radiation profiles through the atmosphere

NASA Astrophysics Data System (ADS)

Kraeuchi, Andreas; Philipona, Rolf

2015-04-01

Very promising radiation profile measurements through the atmosphere were made in 2011 with a balloon borne short- and longwave net radiometer. New and improved radiation sensors from Kipp&Zonen are now used in a glider aircraft together with a standard Swiss radiosonde from Meteolabor AG. This new return glider radiosonde (RG-R), is lifted up with double balloon technique to prevent pendulum motion and to keep the radiation instruments as horizontal as possible during the ascent measuring phase. The RG-R is equipped with a mechanism that allows to release the radiosonde at a preset altitude, and an autopilot allowing to fly the radiosonde back to the launch site and to land it savely with a parachute at a preset location. The return glider radiosonde technique as well as new measurement possibilities will be shown. First measurements show temperature, humidity and radiation profiles through the atmosphere up to 30 hPa (24 km) during different atmospheric conditions. Radiation profiles during different daytimes show possibilities with respect to temporal resolution of vertical radiation profiles trough the atmosphere.

Drug safety evaluation of naltrexone/bupropion for the treatment of obesity.

PubMed

Verpeut, Jessica L; Bello, Nicholas T

2014-06-01

Obesity is a known health risk for the development of several preventable diseases. Obesity-related metabolic alterations negatively impact different physiological mechanisms, which supports the rationale for the use of combined drug therapy. Naltrexone is an opioid antagonist for the treatment of opioid and alcohol dependency, whereas bupropion is a norepinephrine/dopamine reuptake inhibitor used to treat depression and smoking cessation. Although not effective as individual monotherapies for obesity, naltrexone and bupropion in combination produce weight loss and a metabolic profile beneficial for the potential treatment of obesity. This review examines the safety and antiobesity effects of naltrexone and bupropion alone and in combination. It reviews the results of four Phase III clinical trials of a novel fixed dose of sustained-released naltrexone/bupropion. Naltrexone/bupropion has a greater weight loss efficacy than two FDA-approved medications, orlistat and lorcaserin. Although the weight loss produced by phentermine/topiramate is superior to naltrexone/bupropion, the safety profile of naltrexone/bupropion has less severe adverse effects. In addition, naltrexone/bupropion is well tolerated, with nausea being the most reported adverse event. Unlike other centrally acting medications, lorcaserin and phentermine/topiramate, naltrexone/bupropion has no abuse potential.

Observation of the impulse phase of a simple flare

NASA Technical Reports Server (NTRS)

Tandberg-Hanssen, E.; Reichmann, E. J.; Teuber, D. L.; Moore, R. L.; Kaufmann, P.; Orwig, L. E.; Zirin, H.

1984-01-01

The paper presents a broad range of complementary observations (SMM and ground-based) of the onset and impulsive phase of the fairly large (1B, M1.2) but simple two-ribbon flare which occurred at 19:15 UT on November 1, 1980 in the northern part of the active region Boulder No. AR2776. It is found that the overall magnetic field configuration in which the flare occurred was a fairly simple, closed arch containing nonpotential substructure; the flare occurred spontaneously within the arch (it was not triggered by emerging magnetic flux). The two major spikes of the impulsive energy release are examined, and the three immediate products of this energy release are discussed.

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

NASA Astrophysics Data System (ADS)

Abolfathi, Bela; Aguado, D. S.; Aguilar, Gabriela; Allende Prieto, Carlos; Almeida, Andres; Tasnim Ananna, Tonima; Anders, Friedrich; Anderson, Scott F.; Andrews, Brett H.; Anguiano, Borja; Aragón-Salamanca, Alfonso; Argudo-Fernández, Maria; Armengaud, Eric; Ata, Metin; Aubourg, Eric; Avila-Reese, Vladimir; Badenes, Carles; Bailey, Stephen; Balland, Christophe; Barger, Kathleen A.; Barrera-Ballesteros, Jorge; Bartosz, Curtis; Bastien, Fabienne; Bates, Dominic; Baumgarten, Falk; Bautista, Julian; Beaton, Rachael; Beers, Timothy C.; Belfiore, Francesco; Bender, Chad F.; Bernardi, Mariangela; Bershady, Matthew A.; Beutler, Florian; Bird, Jonathan C.; Bizyaev, Dmitry; Blanc, Guillermo A.; Blanton, Michael R.; Blomqvist, Michael; Bolton, Adam S.; Boquien, Médéric; Borissova, Jura; Bovy, Jo; Andres Bradna Diaz, Christian; Nielsen Brandt, William; Brinkmann, Jonathan; Brownstein, Joel R.; Bundy, Kevin; Burgasser, Adam J.; Burtin, Etienne; Busca, Nicolás G.; Cañas, Caleb I.; Cano-Díaz, Mariana; Cappellari, Michele; Carrera, Ricardo; Casey, Andrew R.; Cervantes Sodi, Bernardo; Chen, Yanping; Cherinka, Brian; Chiappini, Cristina; Doohyun Choi, Peter; Chojnowski, Drew; Chuang, Chia-Hsun; Chung, Haeun; Clerc, Nicolas; Cohen, Roger E.; Comerford, Julia M.; Comparat, Johan; Correa do Nascimento, Janaina; da Costa, Luiz; Cousinou, Marie-Claude; Covey, Kevin; Crane, Jeffrey D.; Cruz-Gonzalez, Irene; Cunha, Katia; da Silva Ilha, Gabriele; Damke, Guillermo J.; Darling, Jeremy; Davidson, James W., Jr.; Dawson, Kyle; de Icaza Lizaola, Miguel Angel C.; de la Macorra, Axel; de la Torre, Sylvain; De Lee, Nathan; de Sainte Agathe, Victoria; Deconto Machado, Alice; Dell’Agli, Flavia; Delubac, Timothée; Diamond-Stanic, Aleksandar M.; Donor, John; José Downes, Juan; Drory, Niv; du Mas des Bourboux, Hélion; Duckworth, Christopher J.; Dwelly, Tom; Dyer, Jamie; Ebelke, Garrett; Davis Eigenbrot, Arthur; Eisenstein, Daniel J.; Elsworth, Yvonne P.; Emsellem, Eric; Eracleous, Michael; Erfanianfar, Ghazaleh; Escoffier, Stephanie; Fan, Xiaohui; Fernández Alvar, Emma; Fernandez-Trincado, J. G.; Cirolini, Rafael Fernando; Feuillet, Diane; Finoguenov, Alexis; Fleming, Scott W.; Font-Ribera, Andreu; Freischlad, Gordon; Frinchaboy, Peter; Fu, Hai; Gómez Maqueo Chew, Yilen; Galbany, Lluís; García Pérez, Ana E.; Garcia-Dias, R.; García-Hernández, D. A.; Garma Oehmichen, Luis Alberto; Gaulme, Patrick; Gelfand, Joseph; Gil-Marín, Héctor; Gillespie, Bruce A.; Goddard, Daniel; González Hernández, Jonay I.; Gonzalez-Perez, Violeta; Grabowski, Kathleen; Green, Paul J.; Grier, Catherine J.; Gueguen, Alain; Guo, Hong; Guy, Julien; Hagen, Alex; Hall, Patrick; Harding, Paul; Hasselquist, Sten; Hawley, Suzanne; Hayes, Christian R.; Hearty, Fred; Hekker, Saskia; Hernandez, Jesus; Hernandez Toledo, Hector; Hogg, David W.; Holley-Bockelmann, Kelly; Holtzman, Jon A.; Hou, Jiamin; Hsieh, Bau-Ching; Hunt, Jason A. S.; Hutchinson, Timothy A.; Hwang, Ho Seong; Jimenez Angel, Camilo Eduardo; Johnson, Jennifer A.; Jones, Amy; Jönsson, Henrik; Jullo, Eric; Sakil Khan, Fahim; Kinemuchi, Karen; Kirkby, David; Kirkpatrick, Charles C., IV; Kitaura, Francisco-Shu; Knapp, Gillian R.; Kneib, Jean-Paul; Kollmeier, Juna A.; Lacerna, Ivan; Lane, Richard R.; Lang, Dustin; Law, David R.; Le Goff, Jean-Marc; Lee, Young-Bae; Li, Hongyu; Li, Cheng; Lian, Jianhui; Liang, Yu; Lima, Marcos; Lin, Lihwai; Long, Dan; Lucatello, Sara; Lundgren, Britt; Mackereth, J. Ted; MacLeod, Chelsea L.; Mahadevan, Suvrath; Geimba Maia, Marcio Antonio; Majewski, Steven; Manchado, Arturo; Maraston, Claudia; Mariappan, Vivek; Marques-Chaves, Rui; Masseron, Thomas; Masters, Karen L.; McDermid, Richard M.; McGreer, Ian D.; Melendez, Matthew; Meneses-Goytia, Sofia; Merloni, Andrea; Merrifield, Michael R.; Meszaros, Szabolcs; Meza, Andres; Minchev, Ivan; Minniti, Dante; Mueller, Eva-Maria; Muller-Sanchez, Francisco; Muna, Demitri; Muñoz, Ricardo R.; Myers, Adam D.; Nair, Preethi; Nandra, Kirpal; Ness, Melissa; Newman, Jeffrey A.; Nichol, Robert C.; Nidever, David L.; Nitschelm, Christian; Noterdaeme, Pasquier; O’Connell, Julia; Oelkers, Ryan James; Oravetz, Audrey; Oravetz, Daniel; Aquino Ortíz, Erik; Osorio, Yeisson; Pace, Zach; Padilla, Nelson; Palanque-Delabrouille, Nathalie; Alonso Palicio, Pedro; Pan, Hsi-An; Pan, Kaike; Parikh, Taniya; Pâris, Isabelle; Park, Changbom; Peirani, Sebastien; Pellejero-Ibanez, Marcos; Penny, Samantha; Percival, Will J.; Perez-Fournon, Ismael; Petitjean, Patrick; Pieri, Matthew M.; Pinsonneault, Marc; Pisani, Alice; Prada, Francisco; Prakash, Abhishek; Queiroz, Anna Bárbara de Andrade; Raddick, M. Jordan; Raichoor, Anand; Barboza Rembold, Sandro; Richstein, Hannah; Riffel, Rogemar A.; Riffel, Rogério; Rix, Hans-Walter; Robin, Annie C.; Rodríguez Torres, Sergio; Román-Zúñiga, Carlos; Ross, Ashley J.; Rossi, Graziano; Ruan, John; Ruggeri, Rossana; Ruiz, Jose; Salvato, Mara; Sánchez, Ariel G.; Sánchez, Sebastián F.; Sanchez Almeida, Jorge; Sánchez-Gallego, José R.; Santana Rojas, Felipe Antonio; Santiago, Basílio Xavier; Schiavon, Ricardo P.; Schimoia, Jaderson S.; Schlafly, Edward; Schlegel, David; Schneider, Donald P.; Schuster, William J.; Schwope, Axel; Seo, Hee-Jong; Serenelli, Aldo; Shen, Shiyin; Shen, Yue; Shetrone, Matthew; Shull, Michael; Silva Aguirre, Víctor; Simon, Joshua D.; Skrutskie, Mike; Slosar, Anže; Smethurst, Rebecca; Smith, Verne; Sobeck, Jennifer; Somers, Garrett; Souter, Barbara J.; Souto, Diogo; Spindler, Ashley; Stark, David V.; Stassun, Keivan; Steinmetz, Matthias; Stello, Dennis; Storchi-Bergmann, Thaisa; Streblyanska, Alina; Stringfellow, Guy S.; Suárez, Genaro; Sun, Jing; Szigeti, Laszlo; Taghizadeh-Popp, Manuchehr; Talbot, Michael S.; Tang, Baitian; Tao, Charling; Tayar, Jamie; Tembe, Mita; Teske, Johanna; Thakar, Aniruddha R.; Thomas, Daniel; Tissera, Patricia; Tojeiro, Rita; Tremonti, Christy; Troup, Nicholas W.; Urry, Meg; Valenzuela, O.; van den Bosch, Remco; Vargas-González, Jaime; Vargas-Magaña, Mariana; Vazquez, Jose Alberto; Villanova, Sandro; Vogt, Nicole; Wake, David; Wang, Yuting; Weaver, Benjamin Alan; Weijmans, Anne-Marie; Weinberg, David H.; Westfall, Kyle B.; Whelan, David G.; Wilcots, Eric; Wild, Vivienne; Williams, Rob A.; Wilson, John; Wood-Vasey, W. M.; Wylezalek, Dominika; Xiao, Ting; Yan, Renbin; Yang, Meng; Ybarra, Jason E.; Yèche, Christophe; Zakamska, Nadia; Zamora, Olga; Zarrouk, Pauline; Zasowski, Gail; Zhang, Kai; Zhao, Cheng; Zhao, Gong-Bo; Zheng, Zheng; Zheng, Zheng; Zhou, Zhi-Min; Zhu, Guangtun; Zinn, Joel C.; Zou, Hu

2018-04-01

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as “The Cannon” and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.

Producing superfluid circulation states using phase imprinting

NASA Astrophysics Data System (ADS)

Kumar, Avinash; Dubessy, Romain; Badr, Thomas; De Rossi, Camilla; de Goër de Herve, Mathieu; Longchambon, Laurent; Perrin, Hélène

2018-04-01

We propose a method to prepare states of given quantized circulation in annular Bose-Einstein condensates (BEC) confined in a ring trap using the method of phase imprinting without relying on a two-photon angular momentum transfer. The desired phase profile is imprinted on the atomic wave function using a short light pulse with a tailored intensity pattern generated with a spatial light modulator. We demonstrate the realization of "helicoidal" intensity profiles suitable for this purpose. Due to the diffraction limit, the theoretical steplike intensity profile is not achievable in practice. We investigate the effect of imprinting an intensity profile smoothed by a finite optical resolution onto the annular BEC with a numerical simulation of the time-dependent Gross-Pitaevskii equation. This allows us to optimize the intensity pattern for a given target circulation to compensate for the limited resolution.

The Design and Operation of a Slowfall AXCP (Air-Deployed Expendable Current Profiler).

DTIC Science & Technology

1988-05-01

Control Sensors pressure switch , P/N 607G6 .................................................... 13 Figure 8. Two-dimensional, free-body diagram of the...surface as well as a release mechanism. We then considered using an inexpensive pressure switch to trip the release mechanism. After a market survey...guillotine and pressure switch from the 250 to 300 psi pressure of seawater without resorting to a high precision 0-ring sealing system and pressure

Spatial-phase-modulation-based study of polyvinyl-alcohol/acrylamide photopolymers in the low spatial frequency range.

PubMed

Gallego, Sergi; Márquez, André; Méndez, David; Marini, Stephan; Beléndez, Augusto; Pascual, Inmaculada

2009-08-01

Photopolymers are appealing materials for the fabrication of diffractive optical elements (DOEs). We evaluate the possibilities of polyvinyl-alcohol/acrylamide-based photopolymers to store diffractive elements with low spatial frequencies. We record gratings with different spatial frequencies in the material and analyze the material behavior measuring the transmitted and the reflected orders as a function of exposition. We study two different compositions for the photopolymer, with and without a cross-linker. The values of diffraction efficiency achieved for both compositions make the material suitable to record DOEs with long spatial periods. Assuming a Fermi-Dirac-function-based profile, we fitted the diffracted intensities (up to the eighth order) to obtain the phase profile of the recorded gratings. This analysis shows that it is possible to achieve a phase shift larger than 2pi rad with steep edges in the periodic phase profile. In the case of the measurements in reflection, we have obtained information dealing with the surface profile, which show that it has a smooth shape with an extremely large phase-modulation depth.

Engineering bioceramic microstructure for customized drug delivery

NASA Astrophysics Data System (ADS)

Pacheco Gomez, Hernando Jose

One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was found to correlate with the pore size distribution and surface area. Furthermore, the average rates of sustained release in the period 8-216h from Cris, Rhe and SCPC were: 9.8, 7.2 and 3.5 mug/h of Vanc and 4.5, 5.3 and 3.5 mug/h of Cis, respectively. Nearly inert Cris ceramic showed release kinetics controlled by its hierarchical nano porous structure. On the other hand, the phase composition and surface chemistry of bioactive Rhe or SCPC ceramics overruled the effect of surface area. The relatively low rate of drug release from SCPC was due to the dissolution-back precipitation reaction taking place on the material surface as confirmed by FTIR bands of surface hydroxyapatite layer at 576.5, 596.7 and 620.7 cm-1. Moreover, the solid solution of crystalline phases of SCPC enhanced the bioactivity of the composite. Nuclear Magnetic Resonance (NMR) and cell culture analyses demonstrated that the interactions between the SCPC dissolution products and the released drug did not cause measurable negative effects on the bioactivity of the tested drugs. The therapeutic effects of the SCPC-Cis hybrid were evaluated using a rat model of hepatocellular carcinoma (HCC). Animals were treated by either systemic cisplatin injection (sCis), or with SCPC-Cis hybrid placed adjacent (ADJ) to, or within (IT), the tumor. Five days after implantation 50-55% of the total cisplatin loaded was released from the SCPC-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared to sCis treatment. Severe side effects were observed in animals treated with sCis including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC-Cis treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5-times higher in IT and ADJ groups, respectively, as compared to sCis treated animals. These data demonstrate the SCPC drug delivery system can provide an effective localized treatment for HCC with significantly reduced toxicity compared to systemic drug administration. Moreover, it is possible to tailor drug release kinetics from SCPC hybrids by controlling the crystalline structure of the material and the ratios of Cris and Rhe in the composite.

Effect of palmitic acid on the characteristics and release profiles of rotigotine-loaded microspheres.

PubMed

Wang, Aiping; Liang, Rongcai; Liu, Wanhui; Sha, Chunjie; Li, Youxin; Sun, Kaoxiang

2016-01-01

The initial burst release is a major obstacle to the development of microsphere-formulated drug products. To investigate the influence of palmitic acid on the characteristics and release profiles of rotigotine-loaded poly(d,l-lactide-co-glycolide) microspheres. Rotigotine-loaded microspheres (RMS) were prepared using the oil-in-water emulsion solvent evaporation technique. The in vitro characteristics of the RMS were evaluated with scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and a particle size analyzer. The in vitro drug release and in vivo pharmacokinetics of the RMS were investigated. The SEM results showed that the addition of palmitic acid changed the surface morphology of the microspheres from smooth to dimpled and then to non-smooth as the palmitic acid content increased. DSC revealed the existence of molecularly dispersed forms of palmitic acid in the microspheres. The in vitro and in vivo release profiles indicated that the addition of 5% and 8% palmitic acid significantly decreased the burst release of rotigotine from the microspheres, and the late-stage release was delayed as the palmitic acid content increased across the investigated range (5-15%). The addition of palmitic acid to the microspheres significantly affects the release profile of rotigotine from RMS.

Thermospheric neutral wind profile in moonlit midnight by Lithium release experiments in Japan

NASA Astrophysics Data System (ADS)

Yamamoto, M. Y.; Watanabe, S.; Abe, T.; Kakinami, Y.; Habu, H.; Yamamoto, M.

2015-12-01

Neutral wind profiles were observed in lower thermosphere at about between 90 km and 130 km altitude by using resonance scattering light of moonlit Lithium (Li) vapor released from sounding rockets in midnight (with almost full-moon condition) in 2013 in Japan. As a target of the Daytime Dynamo campaign, Li release experiment was operated at Wallops Flight Facility (WFF) of NASA, U.S.A. in July, 2013 (Pfaff et al., 2015, this meeting), while the same kind of rocket-ground observation campaign in midnight was carried out by using S-520-27/S-310-42 sounding rockets in Uchinoura Space Center (USC) of JAXA, Kagoshima, Japan, also in July 2013.Since imaging signal-to-noise (S/N) condition of the experiment was so severe, we conducted to apply airborne observation for imaging the faint moonlit Li tracers so as to reduce the illuminating intensity of the background skies as an order of magnitude. Two independent methods for calculating the wind profile were applied to the Lithium emission image sequences successfully obtained by the airborne imaging by special Li imagers aboard the airplanes in order to derive precise information of Li tracers motion under the condition of single observation site on a moving aircraft along its flight path at about 12 km altitude in lower stratosphere. Slight attitude-feedback motion of the aircraft's 3-axes attitude changes (rolling, yawing and pitching) was considered for obtaining precise coordinates on each snapshot. Another approach is giving a simple mathematic function for wind profile to resolve the shape displacement of the imaged Li tracers. As a result, a wind profile in moonlit thermosphere was calculated in a range up to about 150 m/s with some fluctuated parts possibly disturbed by wind shears. In the same experiment, another sounding rocket S-310-42 with a TMA canister was also launched from USC/JAXA at about 1 hour before the rocket with carrying the Lithium canisters, thus, we can derive the other 2 profiles determined by the TMA chemical releases in up-leg and down-leg of the flight for the comparison. In this paper, we will report the obtained results of the moonlit Lithium emission intensities as well as method of wind profile calculations and final result of the comparison between the TMA and moonlit Lithium chemical releases in midnight lower thermosphere.

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

2006-01-01

Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

PubMed Central

Koynova, Rumiana; MacDonald, Robert C.

2007-01-01

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30 min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/ phosphatidylserine/cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, ∼40-45°C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer “frustration” which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a “frustrated” bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics. PMID:17559800

Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koynova, Rumiana; MacDonald, Robert C.

2010-01-18

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interacting and mixing with cellular lipids. Here we report our finding that lipid mixtures mimicking biomembrane lipid compositions are superior to pure anionic liposomes in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes), even though they have a much lower negative charge density (and thus lower capacity to neutralize the positive charge of the lipoplex lipids). Flow fluorometry revealed that the portion of DNA released after a 30-min incubation of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic phosphatidylserinemore » or phosphatidylglycerol was 19% and 37%, respectively, whereas a mixture mimicking biomembranes (MM: phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol 45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%, respectively, of the DNA content. A possible reason for this superior power in releasing DNA by the natural lipid mixtures was suggested by structural experiments: while pure anionic lipids typically form lamellae, the natural lipid mixtures exhibited a surprising predilection to form nonlamellar phases. Thus, the MM mixture arranged into lamellar arrays at physiological temperature, but began to convert to the hexagonal phase at a slightly higher temperature, {approx} 40-45 C. A propensity to form nonlamellar phases (hexagonal, cubic, micellar) at close to physiological temperatures was also found with the lipid extracts from natural tissues (from bovine liver, brain, and heart). This result reveals that electrostatic interactions are only one of the factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers to form nonlamellar phases has been described in terms of bilayer 'frustration' which imposes a nonzero intrinsic curvature of the two opposing monolayers. Because the stored curvature elastic energy in a 'frustrated' bilayer seems to be comparable to the binding energy between cationic lipid and DNA, the balance between these two energies could play a significant role in the lipoplex-membrane interactions and DNA release energetics.« less

Metal release profiles of orthodontic bands, brackets, and wires: an in vitro study.

PubMed

Wendl, B; Wiltsche, H; Lankmayr, E; Winsauer, H; Walter, A; Muchitsch, A; Jakse, N; Wendl, M; Wendl, T

2017-11-01

The present study evaluated the temporal release of Co Cr, Mn, and Ni from the components of a typical orthodontic appliance during simulated orthodontic treatment. Several commercially available types of bands, brackets, and wires were exposed to an artificial saliva solution for at least 44 days and the metals released were quantified in regular intervals using inductively coupled plasma quadrupole mass spectrometry (ICP-MS, Elan DRC+, Perkin Elmer, USA). Corrosion products encountered on some products were investigated by a scanning electron microscope equipped with an energy dispersive X-ray microanalyzer (EDX). Bands released the largest quantities of Co, Cr, Mn, and Ni, followed by brackets and wires. Three different temporal metal release profiles were observed: (1) constant, though not necessarily linear release, (2) saturation (metal release stopped after a certain time), and (3) an intermediate release profile that showed signs of saturation without reaching saturation. These temporal metal liberation profiles were found to be strongly dependent on the individual test pieces. The corrosion products which developed on some of the bands after a 6-month immersion in artificial saliva and the different metal release profiles of the investigated bands were traced back to different attachments welded onto the bands. The use of constant release rates will clearly underestimate metal intake by the patient during the first couple of days and overestimate exposure during the remainder of the treatment which is usually several months long. While our data are consistent with heavy metal release by orthodontic materials at levels well below typical dietary intake, we nevertheless recommend the use of titanium brackets and replacement of the band with a tube in cases of severe Ni or Cr allergy.

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

PubMed Central

Sun, Jin; Shi, Jie-Ming; Zhang, Tian-Hong; Gao, Kun; Mao, Jing-Jing; Li, Bing; Sun, Ying-Hua; He, Zhong-Gui

2005-01-01

AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves. PMID:16052686

Dynamic force profile in hydraulic hybrid vehicles: a numerical investigation

NASA Astrophysics Data System (ADS)

Mohaghegh-Motlagh, Amin; Elahinia, Mohammad H.

2010-04-01

A hybrid hydraulic vehicle (HHV) combines a hydraulic sub-system with the conventional drivetrain in order to improve fuel economy for heavy vehicles. The added hydraulic module manages the storage and release of fluid power necessary to assist the motion of the vehicle. The power collected by a pump/motor (P/M) from the regenerative braking phase is stored in a high-pressure accumulator and then released by the P/M to the driveshaft during the acceleration phase. This technology is effective in significantly improving fuel-economy for heavy-class vehicles with frequent stop-and-go drive schedules. Despite improved fuel economy and higher vehicle acceleration, noise and vibrations are one of the main problems of these vehicles. The dual function P/Ms are the main source of noise and vibration in a HHV. This study investigates the dynamics of a P/M and particularly the profile and frequency-dependence of the dynamic forces generated by a bent-axis P/M unit. To this end, the fluid dynamics side of the problem has been simplified for investigating the system from a dynamics perspective. A mathematical model of a bent axis P/M has been developed to investigate the cause of vibration and noise in HHVs. The forces are calculated in time and frequency domains. The results of this work can be used to study the vibration response of the chassis and to design effective vibration isolation systems for HHVs.

Hydrology and Soil Manipulations of Iron-Rich Ditch Mesocosms Provide Little Evidence of Phosphorus Capture within the Profile.

PubMed

Ruppert, David E; Needelman, Brian A; Kleinman, Peter J A; Rabenhorst, Martin C; Momen, Bahram; Wester, David B

2017-05-01

Agricultural drainage ditches function as first-order streams and affect nutrient management. Soil mesocosms from a ditch featuring a vertical (increasing upward) gradient in iron (Fe) and phosphorus (P) were subjected to hydraulic and soil treatments. These manipulations mimicked aspects of dredging and controlled drainage and inspected the soil release and retention of P. Treatments did not remove P from simulated groundwater. Throughput water either gained in P (lack of dredging, especially under Fe-reducing conditions) or had P concentrations indistinguishable from input water (dredging). Undredged mesocosms, when Fe-reducing, released Fe and P simultaneously. Simultaneous release of P and Fe from our Fe-reducing mesocosms indicates a mechanism whereby P capture occurs by Fe precipitation upon emergence to aerated surficial waters. Upwelling and surficial phases of ditch hydrology and the lowering of the ditch surface on dredging complicate interpretation of traditional means of describing ditch P retention and release. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Electrical 2π phase control of infrared light in a 350-nm footprint using graphene plasmons

NASA Astrophysics Data System (ADS)

Woessner, Achim; Gao, Yuanda; Torre, Iacopo; Lundeberg, Mark B.; Tan, Cheng; Watanabe, Kenji; Taniguchi, Takashi; Hillenbrand, Rainer; Hone, James; Polini, Marco; Koppens, Frank H. L.

2017-07-01

Modulating the amplitude and phase of light is at the heart of many applications such as wavefront shaping, transformation optics, phased arrays, modulators and sensors. Performing this task with high efficiency and small footprint is a formidable challenge. Metasurfaces and plasmonics are promising, but metals exhibit weak electro-optic effects. Two-dimensional materials, such as graphene, have shown great performance as modulators with small drive voltages. Here, we show a graphene plasmonic phase modulator that is capable of tuning the phase between 0 and 2π in situ. The device length of 350 nm is more than 30 times shorter than the 10.6 μm free-space wavelength. The modulation is achieved by spatially controlling the plasmon phase velocity in a device where the spatial carrier density profile is tunable. We provide a scattering theory for plasmons propagating through spatial density profiles. This work constitutes a first step towards two-dimensional transformation optics for ultracompact modulators and biosensing.

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC.

PubMed

Sankalia, Jolly M; Sankalia, Mayur G; Mashru, Rajashree C

2008-07-02

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

Control of electromagnetically induced transparency via a hybrid semiconductor quantum dot-vanadium dioxide nanoparticle system

NASA Astrophysics Data System (ADS)

Zamani, Naser; Hatef, Ali; Nadgaran, Hamid; Keshavarz, Alireza

2017-07-01

We numerically investigate the electromagnetically induced transparency (EIT) of a hybrid system consisting of a three-level quantum dot (QD) in the vicinity of vanadium dioxide nanoparticle (VO2NP). VO2NP has semiconductor and metallic phases where the transition between the two phases occurs around a critical temperature. When the QD-VO2NP hybrid system interacts with continuous wave laser fields in an infrared regime, it supports a coherent coupling of exciton-polariton and exciton-plasmon polariton in semiconductor and metal phases of VO2NP, respectively. In our calculations a filling fraction factor controls the VO2NP phase transition. A probe and control laser field configuration is studied for the hybrid system to measure the absorption of QD through the filling fraction factor manipulations. We show that for the VO2NP semiconductor phase and proper geometrical configuration, the absorption spectrum profile of the QD represents an EIT with two peaks and a clear minimum. These two peaks merge to one through the VO2NP phase transition to metal. We also show that the absorption spectrum profile is modified by different orientations of the laser fields with the axis of the QD-VO2NP hybrid system. The innovation in comparison to other research in the field is that robust variation in the absorption profile through EIT is due to the phase transition in VO2NP without any structural change in the QD-VO2NP hybrid system. Our results can be employed to design nanothermal sensors, optical nanoswitches, and energy transfer devices.

Bioadhesive hydrogels for cosmetic applications.

PubMed

Parente, M E; Ochoa Andrade, A; Ares, G; Russo, F; Jiménez-Kairuz, Á

2015-10-01

The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Weathering of the New Albany Shale, Kentucky: II. Redistribution of minor and trace elements

USGS Publications Warehouse

Tuttle, M.L.W.; Breit, G.N.; Goldhaber, M.B.

2009-01-01

During weathering, elements enriched in black shale are dispersed in the environment by aqueous and mechanical transport. Here a unique evaluation of the differential release, transport, and fate of Fe and 15 trace elements during progressive weathering of the Devonian New Albany Shale in Kentucky is presented. Results of chemical analyses along a weathering profile (unweathered through progressively weathered shale to soil) describe the chemically distinct pathways of the trace elements and the rate that elements are transferred into the broader, local environment. Trace elements enriched in the unweathered shale are in massive or framboidal pyrite, minor sphalerite, CuS and NiS phases, organic matter and clay minerals. These phases are subject to varying degrees and rates of alteration along the profile. Cadmium, Co, Mn, Ni, and Zn are removed from weathered shale during sulfide-mineral oxidation and transported primarily in aqueous solution. The aqueous fluxes for these trace elements range from 0.1 g/ha/a (Cd) to 44 g/ha/a (Mn). When hydrologic and climatic conditions are favorable, solutions seep to surface exposures, evaporate, and form Fe-sulfate efflorescent salts rich in these elements. Elements that remain dissolved in the low pH (<4) streams and groundwater draining New Albany Shale watersheds become fixed by reactions that increase pH. Neutralization of the weathering solution in local streams results in elements being adsorbed and precipitated onto sediment surfaces, resulting in trace element anomalies. Other elements are strongly adsorbed or structurally bound to solid phases during weathering. Copper and U initially are concentrated in weathering solutions, but become fixed to modern plant litter in soil formed on New Albany Shale. Molybdenum, Pb, Sb, and Se are released from sulfide minerals and organic matter by oxidation and accumulate in Fe-oxyhydroxide clay coatings that concentrate in surface soil during illuviation. Chromium, Ti, and V are strongly correlated with clay abundance and considered to be in the structure of illitic clay. Illite undergoes minimal alteration during weathering and is concentrated during illuvial processes. Arsenic concentration increases across the weathering profile and is associated with the succession of secondary Fe(III) minerals that form with progressive weathering. Detrital fluxes of particle-bound trace elements range from 0.1 g/ha/a (Sb) to 8 g/ha/a (Mo). Although many of the elements are concentrated in the stream sediments, changes in pH and redox conditions along the sediment transport path could facilitate their release for aqueous transport.

Application of mixture experimental design in the formulation and optimization of matrix tablets containing carbomer and hydroxy-propylmethylcellulose.

PubMed

Petrovic, Aleksandra; Cvetkovic, Nebojsa; Ibric, Svetlana; Trajkovic, Svetlana; Djuric, Zorica; Popadic, Dragica; Popovic, Radmila

2009-12-01

Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

PubMed

Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

2017-07-01

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

Quantitative tomographic measurements of opaque multiphase flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

GEORGE,DARIN L.; TORCZYNSKI,JOHN R.; SHOLLENBERGER,KIM ANN

2000-03-01

An electrical-impedance tomography (EIT) system has been developed for quantitative measurements of radial phase distribution profiles in two-phase and three-phase vertical column flows. The EIT system is described along with the computer algorithm used for reconstructing phase volume fraction profiles. EIT measurements were validated by comparison with a gamma-densitometry tomography (GDT) system. The EIT system was used to accurately measure average solid volume fractions up to 0.05 in solid-liquid flows, and radial gas volume fraction profiles in gas-liquid flows with gas volume fractions up to 0.15. In both flows, average phase volume fractions and radial volume fraction profiles from GDTmore » and EIT were in good agreement. A minor modification to the formula used to relate conductivity data to phase volume fractions was found to improve agreement between the methods. GDT and EIT were then applied together to simultaneously measure the solid, liquid, and gas radial distributions within several vertical three-phase flows. For average solid volume fractions up to 0.30, the gas distribution for each gas flow rate was approximately independent of the amount of solids in the column. Measurements made with this EIT system demonstrate that EIT may be used successfully for noninvasive, quantitative measurements of dispersed multiphase flows.« less

Shock compression and release of a-axis magnesium single crystals: Anisotropy and time dependent inelastic response

DOE PAGES

Renganathan, P.; Winey, J. M.; Gupta, Y. M.

2017-01-19

Here, to gain insight into inelastic deformation mechanisms for shocked hexagonal close-packed (hcp) metals, particularly the role of crystal anisotropy, magnesium (Mg) single crystals were subjected to shock compression and release along the a-axis to 3.0 and 4.8 GPa elastic impact stresses. Wave profiles measured at several thicknesses, using laser interferometry, show a sharply peaked elastic wave followed by the plastic wave. Additionally, a smooth and featureless release wave is observed following peak compression. When compared to wave profiles measured previously for c-axis Mg, the elastic wave amplitudes for a-axis Mg are lower for the same propagation distance, and less attenuation of elastic wave amplitude is observed for a given peak stress. The featureless release wave for a-axis Mg is in marked contrast to the structured features observed for c-axis unloading. Numerical simulations, using a time-dependent anisotropic modeling framework, showed that the wave profiles calculated using prismatic slip or (10more » $$\\bar{1}$$2) twinning, individually, do not match the measured compression profiles for a-axis Mg. However, a combination of slip and twinning provides a good overall match to the measured compression profiles. In contrast to compression,prismatic slip alone provides a reasonable match to the measured release wave profiles; (10$$\\bar{1}$$2) twinning due to its uni-directionality is not activated during release. The experimental results and wave profile simulations for a-axis Mg presented here are quite different from the previously published c-axis results, demonstrating the important role of crystal anisotropy on the time-dependent inelastic deformation of Mg single crystals under shock compression and release.« less

Shock compression and release of a-axis magnesium single crystals: Anisotropy and time dependent inelastic response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renganathan, P.; Winey, J. M.; Gupta, Y. M.

Here, to gain insight into inelastic deformation mechanisms for shocked hexagonal close-packed (hcp) metals, particularly the role of crystal anisotropy, magnesium (Mg) single crystals were subjected to shock compression and release along the a-axis to 3.0 and 4.8 GPa elastic impact stresses. Wave profiles measured at several thicknesses, using laser interferometry, show a sharply peaked elastic wave followed by the plastic wave. Additionally, a smooth and featureless release wave is observed following peak compression. When compared to wave profiles measured previously for c-axis Mg, the elastic wave amplitudes for a-axis Mg are lower for the same propagation distance, and less attenuation of elastic wave amplitude is observed for a given peak stress. The featureless release wave for a-axis Mg is in marked contrast to the structured features observed for c-axis unloading. Numerical simulations, using a time-dependent anisotropic modeling framework, showed that the wave profiles calculated using prismatic slip or (10more » $$\\bar{1}$$2) twinning, individually, do not match the measured compression profiles for a-axis Mg. However, a combination of slip and twinning provides a good overall match to the measured compression profiles. In contrast to compression,prismatic slip alone provides a reasonable match to the measured release wave profiles; (10$$\\bar{1}$$2) twinning due to its uni-directionality is not activated during release. The experimental results and wave profile simulations for a-axis Mg presented here are quite different from the previously published c-axis results, demonstrating the important role of crystal anisotropy on the time-dependent inelastic deformation of Mg single crystals under shock compression and release.« less

Dye-doped nanostructure polypyrrole film for electrochemically switching solid-phase microextraction of Ni(II) and ICP-OES analysis of waste water.

PubMed

Shamaeli, Ehsan; Alizadeh, Naader

2012-01-01

A nanostructure fiber based on conducting polypyrrole synthesized by an electrochemical method has been developed, and used for electrochemically switching solid-phase microextraction (ES-SPME). The ES-SPME was prepared by the doping of eriochrome blue in polypyrrole (PPy-ECB) and used for selectively extracting the Ni(II) cation in the presence of some transition and heavy metal ions. The cation-exchange behavior of electrochemically prepared polypyrrole on stainless-steel with and without eriochrome blue (ECB) dye was characterized using ICP-OES analysis. The effects of the scan rate for electrochemical synthesis, uptake and the release potential on the extraction behavior of the PPy-ECB conductive fiber were studied. Uptake and release time profiles show that the process of electrically switched cation exchange could be completed within 250 s. The results of the present study point concerning the possibility of developing a selective extraction process for Ni(II) from waste water was explored using such a nanostructured PPy-ECB film through an electrically switched cation exchange. 2012 © The Japan Society for Analytical Chemistry

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

Controlled release of anticancer drug methotrexate from biodegradable gelatin microspheres.

PubMed

Narayani, R; Rao, K P

1994-01-01

Biodegradable hydrophilic gelatin microspheres containing the anticancer drug methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20 microns) were prepared by polymer dispersion technique and crosslinked with glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of free-flowing powder. About 80 per cent of MTX was incorporated in gelatin microspheres of different sizes. The in vitro release of MTX was investigated in two different media, namely simulated gastric and intestinal fluids. The release profiles indicated that gelatin microspheres released MTX in a zero-order fashion for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal fluid. The rate of release of MTX decreased with increase in the particle size of the microspheres. MTX release was faster in gastric fluid when compared to intestinal fluid.

Exploring the additivity of binaural and monaural masking release.

PubMed

Hall, Joseph W; Buss, Emily; Grose, John H

2011-04-01

Experiment 1 examined comodulation masking release (CMR) for a 700-Hz tonal signal under conditions of N(o)S(o) (noise and signal interaurally in phase) and N(o)S(π) (noise in phase, signal out of phase) stimulation. The baseline stimulus for CMR was either a single 24-Hz wide narrowband noise centered on the signal frequency [on-signal band (OSB)] or the OSB plus, a set of flanking noise bands having random envelopes. Masking noise was either gated or continuous. The CMR, defined with respect to either the OSB or the random noise baseline, was smaller for N(o)S(π) than N(o)S(o) stimulation, particularly when the masker was continuous. Experiment 2 examined whether the same pattern of results would be obtained for a 2000-Hz signal frequency; the number of flanking bands was also manipulated (two versus eight). Results again showed smaller CMR for N(o)S(π) than N(o)S(o) stimulation for both continuous and gated masking noise. The CMR was larger with eight than with two flanking bands, and this difference was greater for N(o)S(o) than N(o)S(π). The results of this study are compatible with serial mechanisms of binaural and monaural masking release, but they indicate that the combined masking release (binaural masking-level difference and CMR) falls short of being additive.

Oxygen Release Induced Chemomechanical Breakdown of Layered Cathode Materials

DOE PAGES

Mu, Linqin; Lin, Ruoqian; Xu, Rong; ...

2018-04-18

Chemical and mechanical properties interplay on the nanometric scale and collectively govern the functionalities of battery materials. Understanding the relationship between the two can inform the design of battery materials with optimal chemomechanical properties for long-life lithium batteries. Herein, we report a mechanism of nanoscale mechanical breakdown in layered oxide cathode materials, originating from oxygen release at high states of charge under thermal abuse conditions. Here, we observe that the mechanical breakdown of charged Li 1-xNi 0.4Mn 0.4Co 0.2O 2 materials proceeds via a two-step pathway involving intergranular and intragranular crack formation. Owing to the oxygen release, sporadic phase transformationsmore » from the layered structure to the spinel and/or rocksalt structures introduce local stress, which initiates microcracks along grain boundaries and ultimately leads to the detachment of primary particles; i.e., intergranular crack formation. Furthermore, intragranular cracks (pores and exfoliations) form, likely due to the accumulation of oxygen vacancies and continuous phase transformations at the surfaces of primary particles. Finally, finite element modeling confirms our experimental observation that the crack formation is attributable to formation of oxygen vacancies, oxygen release, and phase transformations. This study is designed to directly observe the chemomechanical behavior of layered oxide cathode materials and provides a chemical basis for strengthening primary and secondary particles by stabilizing the oxygen anions in the lattice.« less

Oxygen Release Induced Chemomechanical Breakdown of Layered Cathode Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mu, Linqin; Lin, Ruoqian; Xu, Rong

Chemical and mechanical properties interplay on the nanometric scale and collectively govern the functionalities of battery materials. Understanding the relationship between the two can inform the design of battery materials with optimal chemomechanical properties for long-life lithium batteries. Herein, we report a mechanism of nanoscale mechanical breakdown in layered oxide cathode materials, originating from oxygen release at high states of charge under thermal abuse conditions. Here, we observe that the mechanical breakdown of charged Li 1-xNi 0.4Mn 0.4Co 0.2O 2 materials proceeds via a two-step pathway involving intergranular and intragranular crack formation. Owing to the oxygen release, sporadic phase transformationsmore » from the layered structure to the spinel and/or rocksalt structures introduce local stress, which initiates microcracks along grain boundaries and ultimately leads to the detachment of primary particles; i.e., intergranular crack formation. Furthermore, intragranular cracks (pores and exfoliations) form, likely due to the accumulation of oxygen vacancies and continuous phase transformations at the surfaces of primary particles. Finally, finite element modeling confirms our experimental observation that the crack formation is attributable to formation of oxygen vacancies, oxygen release, and phase transformations. This study is designed to directly observe the chemomechanical behavior of layered oxide cathode materials and provides a chemical basis for strengthening primary and secondary particles by stabilizing the oxygen anions in the lattice.« less

Synthesis of amphiphilic tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization directly initiating from cyclic precursors and their application as drug nanocarriers.

PubMed

Wan, Xuejuan; Liu, Tao; Liu, Shiyong

2011-04-11

We report on the facile synthesis of well-defined amphiphilic and thermoresponsive tadpole-shaped linear-cyclic diblock copolymers via ring-opening polymerization (ROP) directly initiating from cyclic precursors, their self-assembling behavior in aqueous solution, and the application of micellar assemblies as controlled release drug nanocarriers. Starting from a trifunctional core molecule containing alkynyl, hydroxyl, and bromine moieties, alkynyl-(OH)-Br, macrocyclic poly(N-isopropylacrylamide) (c-PNIPAM) bearing a single hydroxyl functionality was prepared by atom transfer radical polymerization (ATRP), the subsequent end group transformation into azide functionality, and finally the intramacromolecular ring closure reaction via click chemistry. The target amphiphilic tadpole-shaped linear-cyclic diblock copolymer, (c-PNIPAM)-b-PCL, was then synthesized via the ROP of ε-caprolactone (CL) by directly initiating from the cyclic precursor. In aqueous solution at 20 °C, (c-PNIPAM)-b-PCL self-assembles into spherical micelles consisting of hydrophobic PCL cores and well-solvated coronas of cyclic PNIPAM segments. For comparison, linear diblock copolymer with comparable molecular weight and composition, (l-PNIPAM)-b-PCL, was also synthesized. It was found that the thermoresponsive coronas of micelles self-assembled from (c-PNIPAM)-b-PCL exhibit thermoinduced collapse and aggregation at a lower critical thermal phase transition temperature (T(c)) compared with those of (l-PNIPAM)-b-PCL. Temperature-dependent drug release profiles from the two types of micelles of (c-PNIPAM)-b-PCL and (l-PNIPAM)-b-PCL loaded with doxorubicin (Dox) were measured, and the underlying mechanism for the observed difference in releasing properties was proposed. Moreover, MTT assays revealed that micelles of (c-PNIPAM)-b-PCL are almost noncytotoxic up to a concentration of 1.0 g/L, whereas at the same polymer concentration, micelles loaded with Dox lead to ∼60% cell death. Overall, chain topologies of thermoresponsive block copolymers, that is, (c-PNIPAM)-b-PCL versus (l-PNIPAM)-b-PCL, play considerable effects on the self-assembling and thermal phase transition properties and their functions as controlled release drug nanocarriers.

Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

PubMed

Wulff, R; Rappen, G-M; Koziolek, M; Garbacz, G; Leopold, C S

2015-09-18

The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Do aerosols influence the diurnal variation of H2O2 in the atmosphere?

NASA Astrophysics Data System (ADS)

Liang, H.; Chen, Z.; Wu, Q.; Huang, D.; Zhao, Y.

2013-12-01

Hydrogen peroxide (H2O2) and organic peroxides are crucial reactive species that are involved in the cycling of HOx (OH and HO2) radicals and the formation of secondary inorganic and organic aerosols in the atmosphere. Despite the importance of peroxides, their formation and removal mechanisms with the coexistence of aerosols are as yet less well known. From June 10 to July 15 2013, summertime surface measurements for atmospheric peroxides were simultaneously obtained in urban Beijing (UB) and Gucheng (GC). The UB site is located in the northern downtown of Beijing city, while the GC site is a rural site located in the North China Plain and ~100 km southwest of Beijing. In both sites, the major peroxides were determined to be H2O2, methyl hydroperoxide (MHP), peroxyformic acid (PFA) and peroxyacetic acid (PAA). By comparing the concentrations of PFA and PAA in the gas phase and rainwater, for the first time, we estimated the Henry's law constant for PFA as ~210 M atm-1 at 298 K, a quarter of that for PAA. Interestingly, we observed different H2O2 profiles in the two sites as follows: (i) the average concentration of H2O2 in UB was 50% higher than that in GC; (ii) H2O2 in GC reached its peak concentration at around 15:30, whereas the peak concentration in UB appeared at as late as 21:00; and (iii) the daily variation of H2O2 in GC generally kept consistent with that of O3 and organic peroxides while it was not always the case in UB. These differences indicate a hitherto unrecognized storage-release mechanism for H2O2 in UB, that is, an extra sink in the noontime and an extra source in the early evening. The extra source of H2O2 would enhance the aerosol phase OH radical in the early evening by the Fenton reaction. A box model analysis shows that the impacts of aerosols were majorly responsible to this unrecognized mechanism, although NOx, regional transport and planet boundary layer height also contributed a minor part. Aerosols participated in the storage-release mechanism in two potential ways. The first is the catalytic reaction of aerosol-phase soluble transition metal ions (ATMIs). ATMIs could convert HO2 to either H2O or H2O2, depending on their abundance and composition. In UB, the high ATMIs are presumed to convert most HO2 to H2O in the noontime and to H2O2 in the early evening, resulting in a different diurnal profile of H2O2. The second is the formation and hydrolysis of H2O2-related complex. In the noontime, H2O2 could be taken up onto the aerosols and then combine with organic matters to form complexes such as hydroxyalkyl hydroperoxides and secondary organic aerosols. In the early evening, however, these complexes could hydrolyze to generate H2O2 and release into the gas phase. The impacts of aerosols on H2O2, and probably on HO2 radicals over the polluted regions should be taken into consideration in the atmospheric model.

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

PubMed

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (C_max), and plasma concentrations at the end of the dosing interval (C_τ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80.00 - 125.00%. Bioavailability of OOD was not influenced by concomitant food intake. OOD and OTD were generally well tolerated, a difference between the two products could not be observed. The new 10-mg OOD formulation provides sustained oxycodone plasma concentrations over the dosing interval of 24 hours and is suitable for once-daily administration. Bioavailability of OOD could be classified as comparable to the twice-daily administration of the OTD reference formulation. The new formulation widens and optimizes the range of strong opioid drug products in patient-centered therapy of chronic pain with simplified dosing and better compliance.
.

Preparation, characterization and in vitro evaluation of microemulsion of raloxifene hydrochloride.

PubMed

Golmohammadzadeh, Shiva; Farhadian, Nafiseh; Biriaee, Amir; Dehghani, Faranak; Khameneh, Bahman

2017-10-01

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which is orally used for treatment of osteoporosis and prevention of breast cancer. The drug has low aqueous solubility and bioavailability. The aim of the present study is to formulate and characterize oil-in-water microemulsion systems for oral delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug solvent oil and surfactant, respectively. In the first and second formulations, Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo-ternary phase diagrams showed that the best surfactant/co-surfactant ratios in the first and second formulations were 4:1 and 9:1, respectively. The particle size of all free drug-loaded and drug loaded samples were in the range of 31.25 ± 0.3 nm and 60.9 ± 0.1 nm, respectively. Electrical conductivity coefficient and refractive index of all microemulsion samples confirmed the formation of oil-in-water type of microemulsion. In vitro drug release profile showed that after 24 hours, 46% and 63% of the drug released through the first formulation in 0.1% (w/v) Tween 80 in distilled water as a release medium and phosphate buffer solution (PBS) at pH = 5.5, respectively. These values were changed to 57% and 98% for the second formulation. Results confirmed that the proposed microemulsion system containing RLX could improve and control the drug release profile in comparison to conventional dosage form.

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

PubMed

Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Design and in vitro evaluation of a novel poly(methacrylic acid)/metronidazole antibacterial nanogel as an oral dosage form.

PubMed

Chen, Tao; Chen, Liang; Li, Haicheng; Chen, Yuhui; Guo, Huixin; Shu, Yang; Chen, Zhiyu; Cai, Changhui; Guo, Lina; Zhang, Xianen; Zhou, Lin; Zhong, Qiu

2014-06-01

To overcome the undesirable side-effects of metronidazole (MTZ), ethylene glycol dimethacrylate is used as the cross-linker, and a series of poly(methacrylic acid) (PMAA) nanogels were prepared to load the MTZ. We investigated the morphology, size, in vitro release property in the simulated gastrointestinal medium, long-term antibacterial performance against Bacteroides fragilis, cytotoxicity, stability and activity of this novel MTZ/PMAA nanogel. The results indicate that the MTZ/PMAA nanogel sustained the release of MTZ in long-term antibacterial activity in the simulated gastrointestinal medium. This MTZ/PMAA nanogel exhibits less cytotoxicity than MTZ alone, suggesting that MTZ/PMAA nanogel is a more useful dosage form than MTZ for mild-to-moderate Clostridium difficile infections. The novel aspects of this study include the synthesis of a nanogel and the three-phase study of the release profile, which might be useful for other researchers in this field. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Development of PMMA membranes functionalized with hydroxypropyl-beta-cyclodextrins for controlled drug delivery using a supercritical CO(2)-assisted technology.

PubMed

Temtem, M; Pompeu, D; Jaraquemada, G; Cabrita, E J; Casimiro, T; Aguiar-Ricardo, A

2009-07-06

Cyclodextrin-containing polymers have proved themselves to be useful for controlled release. Herein we describe the preparation of membranes of poly(methylmethacrylate) (PMMA) containing hydroxypropyl-beta-cyclodextrins (HP-beta-CDs) using a supercritical CO(2)-assisted phase inversion method, for potential application as drug delivery devices. Results are reported on the membrane preparation, physical properties, and drug elution profile of a model drug. The polymeric membranes were obtained with HP-beta-CD contents ranging from 0 to 33.4 wt%, by changing the composition of the casting solution, and were further impregnated with ibuprofen using supercritical carbon dioxide (scCO(2)) in batch mode. The influence of the membrane functionalization in the controlled release of ibuprofen was studied by performing in vitro experiments in buffer solution pH at 7.4. The release of the anti-inflammatory drug could be tuned by varying the cyclodextrin content on the membranes.

Shape measurement of objects with large discontinuities and surface isolations using complementary grating projection

NASA Astrophysics Data System (ADS)

Hao, Yudong; Zhao, Yang; Li, Dacheng

1999-11-01

Grating projection 3D profilometry has three major problems that have to be handled with great care. They are local shadows, phase discontinuities and surface isolations. Carrying no information, shadow areas give us no clue about the profile there. Phase discontinuities often baffle phase unwrappers because they may be generated for several reasons difficult to distinguish. Spatial phase unwrapping will inevitably fail if the object under teste have surface isolations. In this paper, a complementary grating projection profilometry is reported, which attempts to tackle the three aforementioned problems simultaneously. This technique involves projecting two grating patterns form both sides of the CCD camera. Phase unwrapping is carried out pixel by pixel using the two phase maps based on the excess fraction method, which is immune to phase discontinuities or surface isolations. Complementary projection makes sure that no area in the visible volume of CCD is devoid of fringe information, although in some cases a small area of the reconstructed profile is of low accuracy compared with others. The system calibration procedures and measurement results are presented in detail, and possible improvement is discussed.

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

DOE PAGES

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.; ...

2017-05-19

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

In vitro assessment of arsenic mobility in historical mine waste dust using simulated lung fluid.

PubMed

Martin, Rachael; Dowling, Kim; Nankervis, Scott; Pearce, Dora; Florentine, Singarayer; McKnight, Stafford

2018-06-01

Exposure studies have linked arsenic (As) ingestion with disease in mining-affected populations; however, inhalation of mine waste dust as a pathway for pulmonary toxicity and systemic absorption has received limited attention. A biologically relevant extractant was used to assess the 24-h lung bioaccessibility of As in dust isolated from four distinct types of historical gold mine wastes common to regional Victoria, Australia. Mine waste particles less than 20 µm in size (PM 20 ) were incubated in a simulated lung fluid containing a major surface-active component found in mammalian lungs, dipalmitoylphosphatidylcholine. The supernatants were extracted, and their As contents measured after 1, 2, 4, 8 and 24 h. The resultant As solubility profiles show rapid dissolution followed by a more modest increasing trend, with between 75 and 82% of the total 24-h bioaccessible As released within the first 8 h. These profiles are consistent with the solubility profile of scorodite, a secondary As-bearing phase detected by X-ray diffraction in one of the investigated waste materials. Compared with similar studies, the cumulative As concentrations released at the 24-h time point were extremely low (range 297 ± 6-3983 ± 396 µg L -1 ), representing between 0.020 ± 0.002 and 0.036 ± 0.003% of the total As in the PM 20 .

New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres.

PubMed

Attia, Mohamed I; Eldehna, Wagdy M; Afifi, Samar A; Keeton, Adam B; Piazza, Gary A; Abdel-Aziz, Hatem A

2017-01-01

The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.

Synchronous behaviour of two interacting oscillatory systems undergoing quasiperiodic route to chaos.

PubMed

Mondal, S; Pawar, S A; Sujith, R I

2017-10-01

Thermoacoustic instability, caused by a positive feedback between the unsteady heat release and the acoustic field in a combustor, is a major challenge faced in most practical combustors such as those used in rockets and gas turbines. We employ the synchronization theory for understanding the coupling between the unsteady heat release and the acoustic field of a thermoacoustic system. Interactions between coupled subsystems exhibiting different collective dynamics such as periodic, quasiperiodic, and chaotic oscillations are addressed. Even though synchronization studies have focused on different dynamical states separately, synchronous behaviour of two coupled systems exhibiting a quasiperiodic route to chaos has not been studied. In this study, we report the first experimental observation of different synchronous behaviours between two subsystems of a thermoacoustic system exhibiting such a transition as reported in Kabiraj et al. [Chaos 22, 023129 (2012)]. A rich variety of synchronous behaviours such as phase locking, intermittent phase locking, and phase drifting are observed as the dynamics of such subsystem change. The observed synchronization behaviour is further characterized using phase locking value, correlation coefficient, and relative mean frequency. These measures clearly reveal the boundaries between different states of synchronization.

Shock initiated reactions of reactive multi-phase blast explosives

NASA Astrophysics Data System (ADS)

Wilson, Dennis; Granier, John; Johnson, Richard; Littrell, Donald

2017-01-01

This paper describes a new class of non-ideal explosive compositions made of perfluoropolyether (PFPE), nanoaluminum, and a micron-size, high mass density, reactive metal. Unlike high explosives, these compositions release energy via a fast self-oxidized combustion wave rather than a true self-sustaining detonation. Their reaction rates are shock dependent and they can be overdriven to change their energy release rate. These compositions are fuel rich and have an extended aerobic energy release phase. The term "reactive multiphase blast" refers to the post-dispersion blast behavior: multiphase in that there are a gas phase that imparts pressure and a solid (particulate) phase that imparts energy and momentum [1]; and reactive in that the hot metal particles react with atmospheric oxygen and the explosive gas products to give an extended pressure pulse. Tantalum-based RMBX formulations were tested in two spherical core-shell configurations - an RMBX shell exploded by a high explosive core, and an RMBX core imploded by a high explosive shell. The fireball and blast characteristics were compared to a C-4 baseline charge.

Safety and pharmacokinetics of veliparib extended-release in patients with advanced solid tumors: a phase I study.

PubMed

Werner, Theresa L; Sachdev, Jasgit; Swisher, Elizabeth M; Gutierrez, Martin; Kittaneh, Muaiad; Stein, Mark N; Xiong, Hao; Dunbar, Martin; Sullivan, Danielle; Komarnitsky, Philip; McKee, Mark; Tan, Antoinette R

2018-05-07

The poly(ADP-ribose) polymerase-1/2 inhibitor veliparib is active against tumors deficient in homologous DNA damage repair. The pharmacokinetics and safety of veliparib extended-release (ER) were evaluated in patients with advanced solid tumors. This phase I study assessed veliparib-ER up to 800 mg once daily or 600 mg twice daily. Dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and safety/tolerability during continuous administration (28-day cycles). Seventy-one patients (n = 53 ovarian, n = 17 breast, n = 1 prostate carcinoma) received veliparib; 50 had deleterious breast cancer susceptibility (BRCA) gene mutations. Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration-time curve compared with veliparib immediate-release (IR). Three patients experienced DLTs (grade 2: asthenia; grade 3: nausea/vomiting, seizure). RP2D and MTD for veliparib-ER were 400 mg BID. The most frequent adverse events (AEs) were nausea (78.9%) and vomiting (50.7%). The most common grade 3/4 treatment-related AEs were as follows: thrombocytopenia (7.0%), nausea, and anemia (4.2% each). Overall, 12 (27.3%) patients with ovarian and 10 (62.5%) patients with breast carcinoma had a partial response. Veliparib-ER, versus veliparib-IR, exhibited an improved pharmacokinetic profile and was well tolerated in patients with ovarian and BRCA-mutated breast cancers. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Multi-point measurement using two-channel reflectometer with antenna switching for study of high-frequency fluctuations in GAMMA 10

NASA Astrophysics Data System (ADS)

Ikezoe, R.; Ichimura, M.; Okada, T.; Itagaki, J.; Hirata, M.; Sumida, S.; Jang, S.; Izumi, K.; Tanaka, A.; Yoshikawa, M.; Kohagura, J.; Sakamoto, M.; Nakashima, Y.

2017-03-01

A two-channel microwave reflectometer system with fast microwave antenna switching capability was developed and applied to the GAMMA 10 tandem mirror device to study high-frequency small-amplitude fluctuations in a hot mirror plasma. The fast switching of the antennas is controlled using PIN diode switches, which offers the significant advantage of reducing the number of high-cost microwave components and digitizers with high bandwidths and large memory that are required to measure the spatiotemporal behavior of the high-frequency fluctuations. The use of two channels rather than one adds the important function of a simultaneous two-point measurement in either the radial direction or the direction of the antenna array to measure the phase profile of the fluctuations along with the normal amplitude profile. The density fluctuations measured using this system clearly showed the high-frequency coherent fluctuations that are associated with Alfvén-ion-cyclotron (AIC) waves in GAMMA 10. A correlation analysis applied to simultaneously measured density fluctuations showed that the phase component that was included in a reflected microwave provided both high coherence and a clear phase difference for the AIC waves, while the amplitude component showed neither significant coherence nor clear phase difference. The axial phase differences of the AIC waves measured inside the hot plasma confirmed the formation of a standing wave structure. The axial variation of the radial profiles was evaluated and a clear difference was found among the AIC waves for the first time, which would be a key to clarify the unknown boundary conditions of the AIC waves.

Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

PubMed

Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

2016-07-01

Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide- co-glycolide- co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology

NASA Astrophysics Data System (ADS)

Sun, Ping; Song, Hua; Cui, Daxiang; Qi, Jun; Xu, Mousheng; Geng, Hongquan

2012-07-01

Matrix metalloproteases are key regulatory molecules in the breakdown of extracellular matrix and in inflammatory processes. Matrix metalloproteinase-1 (MMP-1) can significantly enhance muscle regeneration by promoting the formation of myofibers and degenerating the fibrous tissue. Herein, we prepared novel MMP-1-loaded poly(lactide-co-glycolide-co-caprolactone) (PLGA-PCL) nanoparticles (NPs) capable of sustained release of MMP-1. We established quadratic equations as mathematical models and employed rotatable central composite design and response surface methodology to optimize the preparation procedure of the NPs. Then, characterization of the optimized NPs with respect to particle size distribution, particle morphology, drug encapsulation efficiency, MMP-1 activity assay and in vitro release of MMP-1 from NPs was carried out. The results of mathematical modeling show that the optimal conditions for the preparation of MMP-1-loaded NPs were as follows: 7 min for the duration time of homogenization, 4.5 krpm for the agitation speed of homogenization and 0.4 for the volume ratio of organic solvent phase to external aqueous phase. The entrapment efficiency and the average particle size of the NPs were 38.75 ± 4.74% and 322.7 ± 18.1 nm, respectively. Further scanning electron microscopy image shows that the NPs have a smooth and spherical surface, with mean particle size around 300 nm. The MMP-1 activity assay and in vitro drug release profile of NPs indicated that the bioactivity of the enzyme can be reserved where the encapsulation allows prolonged release of MMP-1 over 60 days. Taken together, we reported here novel PLGA-PCL NPs for sustained release of MMP-1, which may provide an ideal MMP-1 delivery approach for tissue reconstruction therapy.

Development and characterization of colloidal silica-based slow-release permanganate gel (SRP-G): laboratory investigations.

PubMed

Lee, Eung Seok; Gupta, Neha

2014-08-01

Slow-release permanganate (MnO4(-)) gel (SRP-G) is a hyper-saline KMnO4 solution that can be used for treating large, dilute, or deep plumes of chlorinated solvents in groundwater. Ideally, the SRP-G injected into aquifers will slowly gelate to form MnO4(-) gel in situ, and the gel will slowly releases MnO4(-). Objectives of this study were to develop SRP-G using colloidal silica as gelling solution, characterize its gelation and release kinetics, and delineate its dynamics in a saturated sandy media. The SRP-G exhibited a two-phase increase in viscosity: a lag phase characterized by little increase in viscosity followed by a short gelation phase. Gelation lag times of SRP-G solutions increased (from 0.5h to 13d) with decreasing KMnO4 concentrations (from 25 to 8 g L(-1)). Permanganate release from gelated SRP-G increased with increasing KMnO4 concentrations, and was characterized as asymptotic release with initial peak (0.9-2.2 mg min(-1)) followed by more attenuated release. Gelation lag times of SRP-G flowing in sands (linear velocity=2.1md(-1)) increased (1, 3, and 6h) with decreasing KMnO4 concentrations (25.0, 23.0, and 22.9 g L(-1)). Permanganate release from gelated SRP-Gs continued for up to 3d and was characterized as asymptotic release with an initial peak release (∼1.2 g min(-1)) followed by more attenuated release over 70h. Dilution of SRP-G by dispersion in porous media affects gelation and release kinetics. Increasing the silica concentration in the SRP-G may facilitate gelation and extend the duration of MnO4(-) release from emplaced SRP-G in porous media. Copyright © 2014. Published by Elsevier Ltd.

Liquid Crystalline Nanoparticles as an Ophthalmic Delivery System for Tetrandrine: Development, Characterization, and In Vitro and In Vivo Evaluation

NASA Astrophysics Data System (ADS)

Liu, Rui; Wang, Shuangshuang; Fang, Shiming; Wang, Jialu; Chen, Jingjing; Huang, Xingguo; He, Xin; Liu, Changxiao

2016-05-01

The purpose of this study was to develop novel liquid crystalline nanoparticles (LCNPs) that display improved pre-ocular residence time and ocular bioavailability and that can be used as an ophthalmic delivery system for tetrandrine (TET). The delivery system consisted of three primary components, including glyceryl monoolein, poloxamer 407, and water, and two secondary components, including Gelucire 44/14 and amphipathic octadecyl-quaternized carboxymethyl chitosan. The amount of TET, the amount of glyceryl monoolein, and the ratio of poloxamer 407 to glyceryl monoolein were selected as the factors that were used to optimize the dependent variables, which included encapsulation efficiency and drug loading. A three-factor, five-level central composite design was constructed to optimize the formulation. TET-loaded LCNPs (TET-LCNPs) were characterized to determine their particle size, zeta potential, entrapment efficiency, drug loading capacity, particle morphology, inner crystalline structure, and in vitro drug release profile. Corneal permeation in excised rabbit corneas was evaluated. Pre-ocular retention was determined using a noninvasive fluorescence imaging system. Finally, pharmacokinetic study in the aqueous humor was performed by microdialysis technique. The optimal formulation had a mean particle size of 170.0 ± 13.34 nm, a homogeneous distribution with polydispersity index of 0.166 ± 0.02, a positive surface charge with a zeta potential of 29.3 ± 1.25 mV, a high entrapment efficiency of 95.46 ± 4.13 %, and a drug loading rate of 1.63 ± 0.07 %. Transmission electron microscopy showed spherical particles that had smooth surfaces. Small-angle X-ray scattering profiles revealed an inverted hexagonal phase. The in vitro release assays showed a sustained drug release profile. A corneal permeation study showed that the apparent permeability coefficient of the optimal formulation was 2.03-fold higher than that of the TET solution. Pre-ocular retention capacity study indicated that the retention of LCNPs was significantly longer than that of the solution ( p < 0.01). In addition, a pharmacokinetic study of rabbit aqueous humors demonstrated that the TET-LCNPs showed 2.65-fold higher ocular bioavailability than that of TET solution. In conclusion, a LCNP system could be a promising method for increasing the ocular bioavailability of TET by enhancing its retention time and permeation into the cornea.

Understanding the role of saliva in aroma release from wine by using static and dynamic headspace conditions.

PubMed

Muñoz-González, Carolina; Feron, Gilles; Guichard, Elisabeth; Rodríguez-Bencomo, J José; Martín-Álvarez, Pedro J; Moreno-Arribas, M Victoria; Pozo-Bayón, M Ángeles

2014-08-20

The aim of this work was to determine the role of saliva in wine aroma release by using static and dynamic headspace conditions. In the latter conditions, two different sampling points (t = 0 and t = 10 min) corresponding with oral (25.5 °C) and postoral phases (36 °C) were monitored. Both methodologies were applied to reconstituted dearomatized white and red wines with different nonvolatile wine matrix compositions and a synthetic wine (without matrix effect). All of the wines had the same ethanol concentration and were spiked with a mixture of 45 aroma compounds covering a wide range of physicochemical characteristics at typical wine concentrations. Two types of saliva (human and artificial) or control samples (water) were added to the wines. The adequacy of the two headspace methodologies for the purposes of the study (repeatability, linear ranges, determination coefficients, etc.) was previously determined. After application of different chemometric analysis (ANOVA, LSD, PCA), results showed a significant effect of saliva on aroma release dependent on saliva type (differences between artificial and human) and on wine matrix using static headspace conditions. Red wines were more affected than white and synthetic wines by saliva, specifically human saliva, which provoked a reduction in aroma release for most of the assayed aroma compounds independent of their chemical structure. The application of dynamic headspace conditions using a saliva bioreactor at the two different sampling points (t = 0 and t = 10 min) showed a lesser but significant effect of saliva than matrix composition and a high influence of temperature (oral and postoral phases) on aroma release.

Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

NASA Astrophysics Data System (ADS)

Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

2017-12-01

Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically denitrified at downstream of the injection well. In conclusion, addition of PT and FT into a well under natural gradient condition may be an effective means for remediating high-strength nitrate in groundwater.

Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging

PubMed Central

Isaac, Vera Lucia Borges; Chiari-Andréo, Bruna Galdorfini; Marto, Joana Marques; Moraes, Jemima Daniela Dias; Leone, Beatriz Alves; Corrêa, Marcos Antonio; Ribeiro, Helena Margarida

2015-01-01

The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and the in vitro release profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA. PMID:26788510

Storage and sustained release of volatile substances from a hollow silica matrix

NASA Astrophysics Data System (ADS)

Wang, Jiexin; Ding, Haomin; Tao, Xia; Chen, Jianfeng

2007-06-01

Porous hollow silica nanospheres (PHSNSs) prepared by adopting a nanosized CaCO3 template were utilized for the first time as a novel carrier for the storage and sustained release of volatile substances. Two types of volatile substances, Indian pipal from perfumes and peroxyacetic acid from disinfectants, were selected and then tested by one simple adsorption process with two separate comparative carriers, i.e. activated carbon and solid porous silica. It was demonstrated that a high storage capacity (9.6 mlperfume/mgcarrier) of perfume could be achieved in a PHSNS matrix, which was almost 14 times as much as that of activated carbon. The perfume release profiles showed that PHSNSs exhibited sustained multi-stage release behaviour, while the constant release of activated carbon at a low level was discerned. Further, a Higuchi model study proved that the release process of perfume in both carriers followed a Fickian diffusion mechanism. For peroxyacetic acid as a disinfectant model, PHSNSs also displayed a much better delayed-delivery process than a solid porous silica system owing to the existence of unique hollow frameworks. Therefore, the aforementioned excellent sustained-release behaviours would make PHSNSs a promising carrier for storage and sustained delivery applications of volatile substances.

Development of a Novel Floating In-situ Gelling System for Stomach Specific Drug Delivery of the Narrow Absorption Window Drug Baclofen.

PubMed

R Jivani, Rishad; N Patel, Chhagan; M Patel, Dashrath; P Jivani, Nurudin

2010-01-01

The present study deals with development of a floating in-situ gel of the narrow absorption window drug baclofen. Sodium alginate-based in-situ gelling systems were prepared by dissolving various concentrations of sodium alginate in deionized water, to which varying concentrations of drug and calcium bicarbonate were added. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to check the presence of any interaction between the drug and the excipients. A 3(2) full factorial design was used for optimization. The concentrations of sodium alginate (X1) and calcium bicarbonate (X2) were selected as the independent variables. The amount of the drug released after 1 h (Q1) and 10 h (Q10) and the viscosity of the solution were selected as the dependent variables. The gels were studied for their viscosity, in-vitro buoyancy and drug release. Contour plots were drawn for each dependent variable and check-point batches were prepared in order to get desirable release profiles. The drug release profiles were fitted into different kinetic models. The floating lag time and floating time found to be 2 min and 12 h respectively. A decreasing trend in drug release was observed with increasing concentrations of CaCO3. The computed values of Q1 and Q10 for the check-point batch were 25% and 86% respectively, compared to the experimental values of 27.1% and 88.34%. The similarity factor (f 2) for the check-point batch being 80.25 showed that the two dissolution profiles were similar. The drug release from the in-situ gel follows the Higuchi model, which indicates a diffusion-controlled release. A stomach specific in-situ gel of baclofen could be prepared using floating mechanism to increase the residence time of the drug in stomach and thereby increase the absorption.

Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

PubMed

Johannsson, G; Nilsson, A G; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B E; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Biller, B M K; Monson, J P; Stewart, P M; Lennernäs, H; Skrtic, S

2012-02-01

Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile. The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets. We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers. The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM). The same daily dose of hydrocortisone was administered as OD dual-release or TID. We evaluated cortisol pharmacokinetics. Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004). The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

Numerical modelling of phase-change material used for PV panels cooling

NASA Astrophysics Data System (ADS)

Sellami, Assia; Elotmani, Rabie; Kandoussi, Khalid; Eljouad, Mohamed; Hajjaji, Abdelowahed; Boutaous, M'Hamed

2017-12-01

Passive cooling of a PV solar panel using phase-change material (PCM) may play an important role in increasing efficiency of PV cells. Because it does not need a maintenance and does not release greenhouses gases, PCM seems to be a good way to decrease the among of overheating of PV cell. The aims of this paper describes a detailed multiphysical issue in order to understand the effect of PCM (RT25) in keeping PV cell temperature close to ambient. The study is focused on modeling the heat and mass transfer in a PCM domain by modifying the buoyancy term in momentum equation. Due to a phase-change and free convection, transient incompressible flow is taken into account to explain the dynamic variations of the velocity profile and viscosity distribution. With standard condition of irradiation and heat flux on both sides of the PV panel, a melt front has been tracked by the energy equation, which gives a good argument for the temperature evolution during phase-change.

Spray-dried high-amylose sodium carboxymethyl starch: impact of α-amylase on drug-release profile.

PubMed

Nabais, Teresa; Zaraa, Sarra; Leclair, Grégoire

2016-11-01

Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0 IU/L to 20000 IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f2 > 50) for all but only one of the studied conditions (f2 = 47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1 h or 3 h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected.

An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

PubMed Central

Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

2013-01-01

Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

PubMed

Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

2014-04-01

It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

Facile synthesis of functionalized ionic surfactant templated mesoporous silica for incorporation of poorly water-soluble drug.

PubMed

Li, Jing; Xu, Lu; Yang, Baixue; Wang, Hongyu; Bao, Zhihong; Pan, Weisan; Li, Sanming

2015-08-15

The present paper reported amino group functionalized anionic surfactant templated mesoporous silica (Amino-AMS) for loading and release of poorly water-soluble drug indomethacin (IMC) and carboxyl group functionalized cationic surfactant templated mesoporous silica (Carboxyl-CMS) for loading and release of poorly water-soluble drug famotidine (FMT). Herein, Amino-AMS and Carboxyl-CMS were facilely synthesized using co-condensation method through two types of silane coupling agent. Amino-AMS was spherical nanoparticles, and Carboxyl-CMS was well-formed spherical nanosphere with a thin layer presented at the edge. Drug loading capacity was obviously enhanced when using Amino-AMS and Carboxyl-CMS as drug carriers due to the stronger hydrogen bonding force formed between surface modified carrier and drug. Amino-AMS and Carboxyl-CMS had the ability to transform crystalline state of loaded drug from crystalline phase to amorphous phase. Therefore, IMC loaded Amino-AMS presented obviously faster release than IMC because amorphous phase of IMC favored its dissolution. The application of asymmetric membrane capsule delayed FMT release significantly, and Carboxyl-CMS favored sustained release of FMT due to its long mesoporous channels and strong interaction formed between its carboxyl group and amino group of FMT. Copyright © 2015 Elsevier B.V. All rights reserved.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability.

PubMed

Sun, Jiabei; Bi, Chao; Chan, Hok Man; Sun, Shaoping; Zhang, Qingwen; Zheng, Ying

2013-11-01

The aim of the present study was to blend liquid lipids with solid lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby improving the dispersibility and chemical stability of curcumin, prolonging its antitumour activity and cellular uptake and enhancing its bioavailability. Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure homogenisation with liquid lipid Sefsol-218(®). The morphology, stability and release of curcumin in the optimised formulation were investigated. The anti-cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence spectrophotometry was used to quantify cellular uptake of the drug. The pharmacokinetic profiles of curcumin in SLNs after intravenous administration were studied in rats. Blending Sefsol-218(®) into a lipid matrix reduced the particle size without improving drug loading. An optimised formulation consisting of Dynasan 114(®), Sefsol-218(®), and Pluronic F68(®) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation could be dispersed in water with a mean particle size of 152.8 ± 4.7 nm and a 90% entrapment efficiency. Curcumin displayed a two-phase sustained release profile from C-SLNs with improved chemical stability. Compared to the solubilised solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well as time-dependent increases in intracellular uptake. After intravenous administration to rats, the bioavailability of curcumin was increased by 1.25-fold. C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed. C-SLNs may represent a potentially useful cancer therapeutic curcumin delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

PubMed

Izadifar, Mohammad; Haddadi, Azita; Chen, Xiongbiao; Kelly, Michael E

2015-01-09

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs. Identifying and understanding such factors as the desired release profiles, mechanisms of release, physicochemical characteristics of polymeric nanoparticles, and externally-triggering stimuli are essential for designing and optimizing such delivery systems. This review surveys the recent studies on the desired release profiles of GFs in various tissue engineering applications, elucidates the major release mechanisms and critical factors affecting release profiles, and overviews the role played by the mathematical models for optimizing nano-particulate delivery systems. Potentials of stimuli responsive nanoparticles for spatiotemporal control of GF release are also presented, along with the recent advances in strategies for spatiotemporal control of GF delivery within tissue engineered scaffolds. The recommendation for the future studies to overcome challenges for developing sophisticated particulate delivery systems in tissue engineering is discussed prior to the presentation of conclusions drawn from this paper.

Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

NASA Astrophysics Data System (ADS)

Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

Characterization of drug release from liposomal formulations in ocular fluid.

PubMed

Jafari, M R; Jones, A B; Hikal, A H; Williamson, J S; Wyandt, C M

1998-01-01

The successful application of liposomes in topical ophthalmic drug delivery requires knowledge of vesicle stabilization in the presence of tear fluid. The release of procaine hydrochloride (PCH) from large unilamellar liposomes in the presence of simulated tear fluid was studied in vitro as a function of bilayer lipid content and tear protein composition. Reverse-phase evaporation vesicles were prepared from egg phosphatidylcholine, stearylamine or dicetyl phosphate, and cholesterol. The relationship between lipid composition and encapsulation efficiency, vesicle size, drug leakage upon storage at 4 degrees C, and the release of PCH-loaded liposomes was studied. The encapsulation efficiency was found to be dependent upon the lipid composition used in the liposome preparation. In particular, phosphatidylcholine vesicles containing cholesterol and/or charged lipids had a lower entrapment efficiency than liposomes prepared with phosphatidylcholine alone. However, the drug release rate was reduced significantly by inclusion of cholesterol and/or charged lipids in the liposomes. The release kinetics of the entrapped agent seemed to be a biphasic process and the drug-release in both simulated tear fluid (STF) and pH 7.4 phosphate buffered saline (PBS) solutions followed pseudo first-order kinetics in the early stage of the release profile. The drug-release appeared to be diffusion and/or partition controlled. Drug release from liposomes into STF, pH 7.4 PBS, and five different modified tear formulations was also evaluated. While serum-induced leakage is attributed to high-density lipoprotein-mediated destabilization, it was determined that lactoferrin might be the protein component in tear fluid that has the primary influence on the liposome-entrapped drug release rate. Five local anesthetics, benoxinate, proparacaine, procaine, tetracaine, and benzocaine were entrapped in liposomal vesicles by a reverse-phase evaporation (REV) technique. The release of these structurally similar topical anesthetics entrapped in positively charged liposomes (egg phosphatidylcholine, stearylamine, and cholesterol in a 7:2:1 molar ratio) was evaluated in a simulated tear fluid and pH 7.4 phosphate buffered saline solution. The liposomes appeared to be useful carriers for these drugs to retard their in vitro release in tear fluid and perhaps sustain or control their release in the eye for better therapeutic efficacy. An analysis of the release data demonstrated that for this series of drugs, drug partition coefficient has the largest effect on release rate, with molecular weight exhibiting a smaller effect. Release rate was found to decrease with increased lipophilicity or increased molecular weight.

Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

PubMed

Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

2002-04-01

The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

A curious case of the accretion-powered X-ray pulsar GX 1+4

NASA Astrophysics Data System (ADS)

Jaisawal, Gaurava K.; Naik, Sachindra; Gupta, Shivangi; Chenevez, Jérôme; Epili, Prahlad

2018-04-01

We present detailed spectral and timing studies using a NuSTAR observation of GX 1+4 in October 2015 during an intermediate intensity state. The measured spin period of 176.778 s is found to be one of the highest values since its discovery. In contrast to a broad sinusoidal-like pulse profile, a peculiar sharp peak is observed in profiles below ˜25 keV. The profiles at higher energies are found to be significantly phase-shifted compared to the soft X-ray profiles. Broadband energy spectra of GX 1+4, obtained from NuSTAR and Swift observations, are described with various continuum models. Among these, a two component model consisting of a bremsstrahlung and a blackbody component is found to best-fit the phase-averaged and phase-resolved spectra. Physical models are also used to investigate the emission mechanism in the pulsar, which allows us to estimate the magnetic field strength to be in ˜(5-10)× 1012 G range. Phase-resolved spectroscopy of NuSTAR observation shows a strong blackbody emission component in a narrow pulse phase range. This component is interpreted as the origin of the peculiar peak in the pulse profiles below ≤25 keV. The size of emitting region is calculated to be ˜400 m. The bremsstrahlung component is found to dominate in hard X-rays and explains the nature of simple profiles at high energies.

A curious case of the accretion-powered X-ray pulsar GX 1+4

NASA Astrophysics Data System (ADS)

Jaisawal, Gaurava K.; Naik, Sachindra; Gupta, Shivangi; Chenevez, Jérôme; Epili, Prahlad

2018-07-01

We present detailed spectral and timing studies using a NuSTAR observation of GX 1+4 in 2015 October during an intermediate-intensity state. The measured spin period of 176.778 s is found to be one of the highest values since its discovery. In contrast to a broad sinusoidal-like pulse profile, a peculiar sharp peak is observed in profiles below ˜25 keV. The profiles at higher energies are found to be significantly phase shifted compared to the soft X-ray profiles. Broad-band energy spectra of GX 1+4, obtained from NuSTAR and Swift observations, are described with various continuum models. Among these, a two-component model consisting of a bremsstrahlung and a blackbody component is found to best fit the phase-averaged and phase-resolved spectra. Physical models are also used to investigate the emission mechanism in the pulsar, which allows us to estimate the magnetic field strength to be in ˜(5-10) × 1012 G range. Phase-resolved spectroscopy of NuSTAR observation shows a strong blackbody emission component in a narrow pulse phase range. This component is interpreted as the origin of the peculiar peak in the pulse profiles below ≤25 keV. The size of emitting region is calculated to be ˜400 m. The bremsstrahlung component is found to dominate in hard X-rays and explains the nature of simple profiles at high energies.

Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine.

PubMed

Pacheco, Daniela P; Amaral, Maria H; Reis, Rui L; Marques, Alexandra P; Correlo, Vítor M

2015-01-15

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents' models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system. Copyright © 2014 Elsevier B.V. All rights reserved.

Distribution of some organic components in two forest soils profiles with evidence of soil organic matter leaching.

NASA Astrophysics Data System (ADS)

Álvarez-Romero, Marta; Papa, Stefania; Lozano-García, Beatriz; Parras-Alcántara, Luis; Coppola, Elio

2015-04-01

Soil stores organic carbon more often than we can find in living vegetation and atmosphere together. This reservoir is not inert, but it is constantly in a dynamic phase of inputs and losses. Soil organic carbon mainly depends on land cover, environment conditions and soil properties. After soil deposition, the organic residues of different origin and nature, the Soil Organic Matter (SOM) can be seen involved in two different processes during the pedogenesis: mineralization and humification. The transport process along profile happens under certain conditions such as deposition of high organic residues amount on the top soil, high porosity of the soil caused by sand or skeleton particles, that determine a water strong infiltrating capacity, also, extreme temperatures can slow or stop the mineralization and/or humification process in one intermediate step of the degradation process releasing organic metabolites with high or medium solubility and high loads of water percolating in relation to intense rainfall. The transport process along soil profile can take many forms that can end in the formation of Bh horizons (h means accumulation of SOM in depth). The forest cover nature influence to the quantity and quality of the organic materials deposited with marked differences between coniferous and deciduous especially in relation to resistance to degradation. Two soils in the Campania region, located in Lago Laceno (Avellino - Italy) with different forest cover (Pinus sp. and Fagus sp.) and that meets the requirements of the place and pedological formation suitable for the formation and accumulation of SOM in depth (Bh horizon) were studied. The different soil C fractions were determinated and were assessed (Ciavatta C. et al. 1990; Dell'Abate M.T. et al. 2002) for each soil profile the Total Extractable Lipids (TEL). Furthermore, the lignin were considered as a major component of soil organic matter (SOM), influencing its pool-size and its turnover, due to the high soil input and the abundance of aromatic structures suggesting chemical recalcitrance, also, cellulose that lignin contents were also assayed. References -Ciavatta C., Govi M., Vittori Antisari L., Sequi P. (1990). Characterization of humified compounds by extraction and fractionation on solid polyvinylpyrrolidone. Journal of Chromatography, 509:141-146. -Dell'Abate M.T., Benedetti A., Trinchera A., Dazzi C. (2002). Humic substances along the profile of two Typic Haploxerert. Geoderma, 107:281-296.

Control of interface reactions in SIC/TI composites

NASA Technical Reports Server (NTRS)

Houska, C. R.; Rao, V.

1982-01-01

The reaction between a 0.5 to 1.0 Al film and a thick Ti substrate to form TiAl3 occurs very rapidly on heating to 635 C and causes the Al to be confined to the surface region. After heating to 900 C Ti3Al is formed with little release of Al into alpha Ti. Further annealing at 900 C eventually causes the Ti3Al phase to decompose and a substantial amount of Al is released into alpha Ti. The interdiffusion coefficient for Al in alpha Ti at 900 C increases by less than one order of magnitude as Al is varied from 0 to 20 at %. These data were obtained from the (101) X-ray diffraction intensity band using polycrystalline samples. Improvements in the analysis of X-ray diffraction data for the determination of composition profiles are discussed.

Chemical composition of volatile aroma metabolites and their glycosylated precursors that can uniquely differentiate individual grape cultivars.

PubMed

Ghaste, Manoj; Narduzzi, Luca; Carlin, Silvia; Vrhovsek, Urska; Shulaev, Vladimir; Mattivi, Fulvio

2015-12-01

Every grape cultivar has its own unique genetic characteristics, leading to the production of a different secondary metabolite profile. Aroma is one of the most important aspects in terms of the quality of grapes and previous studies have assigned specific aromas to particular grape cultivars. In this study we present the molecular profiling of volatile aroma metabolites and their precursors in ten selected genotypes, including six Vitis vinifera cultivars, two American species (Arizonica Texas, Vitis cinerea) and two interspecific crosses. Chemical profiling was achieved through combined use of two orthogonal techniques, GC-MS and LC-HRMS, before and after enzymatic hydrolysis. The results show that both free and glycosidically bound aroma precursors behave differently in each different grape cultivar and species. As many as 66 free aroma volatile molecules (originally existing and released after hydrolysis) were profiled through GC-MS analysis, while 15 glycosylated precursors of volatiles were identified through LC-HRMS and correlation with GC-MS data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bubble dynamics and bubble-induced turbulence of a single-bubble chain

NASA Astrophysics Data System (ADS)

Lee, Joohyoung; Park, Hyungmin

2016-11-01

In the present study, the bubble dynamics and liquid-phase turbulence induced by a chain of bubbles injected from a single nozzle have been experimentally investigated. Using a high-speed two-phase particle image velociemtry, measurements on the bubbles and liquid-phase velocity field are conducted in a transparent tank filled with water, while varying the bubble release frequency from 0.1 to 35 Hz. The tested bubble size ranges between 2.0-3.2 mm, and the corresponding bubble Reynolds number is 590-1100, indicating that it belongs to the regime of path instability. As the release frequency increases, it is found that the global shape of bubble dispersion can be classified into two regimes: from asymmetric (regular) to axisymmetric (irregular). In particular, at higher frequency, the wake vortices of leading bubbles cause an irregular behaviour of the following bubble. For the liquid phase, it is found that a specific trend on the bubble-induced turbulence appears in a strong relation to the above bubble dynamics. Considering this, we try to provide a theoretical model to estimate the liquid-phase turbulence induced by a chain of bubbles. Supported by a Grant funded by Samsung Electronics, Korea.

Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations.

PubMed

Rossi, Alessandra; Conti, Chiara; Colombo, Gaia; Castrati, Luca; Scarpignato, Carmelo; Barata, Pedro; Sandri, Giuseppina; Caramella, Carla; Bettini, Ruggero; Buttini, Francesca; Colombo, Paolo

2016-01-01

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.

Astressin B, a corticotropin-releasing hormone receptor antagonist, accelerates the return to normal luteal function after an inflammatory-like stress challenge in the rhesus monkey.

PubMed

Xiao, Ennian; Xia-Zhang, Linna; Vulliemoz, Nicolas; Rivier, Jean; Ferin, Michel

2007-02-01

Endogenous release of CRH in stress has been associated with a dysfunctional reproductive endocrine axis. In the rhesus monkey, an inflammatory-like stress challenge in the luteal phase decreases luteal secretory function. Here, we tested the effectiveness of astressin B, a nonspecific CRH receptor antagonist, in constraining the deleterious impact of a 10-d lipopolysaccharide (LPS) challenge on the menstrual cycle. Two protocols were carried out in nine animals. In the first, the animals, after showing two normal consecutive control cycles, were injected daily for 10 days with LPS (75-125 mug/d) during the luteal phase of the cycle. The animals were followed through the two postchallenge cycles. The second protocol, carried out in the following year, was identical with protocol 1, except that the animals were treated with astressin B (0.45 mg/kg) 1 h before each daily LPS challenge during the luteal phase. Blood samples were obtained daily to document cyclic hormones levels. The LPS challenge significantly decreased luteal progesterone and LH release during the challenge cycle. Inhibition of luteal progesterone extended to the two successive postchallenge cycles. Astressin B treatment prevented luteal LH but not luteal progesterone decrease during the treatment cycle and restored normal progesterone secretion during the two posttreatment cycles. We conclude that the deleterious impact of a short-term inflammatory stress challenge on luteal function is far longer than the stress period itself. Systemic administration of astressin B accelerates the return to normal luteal function, presumably by restoring normal neuroendocrine regulation of gonadotropin secretion.

Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.

PubMed

Arica, Betül; Kaş, H Süheyla; Moghdam, Amir; Akalan, Nejat; Hincal, A Atilla

2005-02-16

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.

Histamine release inhibitory activity of Piper nigrum leaf.

PubMed

Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

2008-10-01

Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique.

PubMed

Onuki, Yoshinori; Jacobs, Igor; Artemov, Dmitri; Kato, Yoshinori

2010-09-01

A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Spatial and temporal characteristics of flare energy release determined from X-ray and radio imaging observations

NASA Technical Reports Server (NTRS)

Hernandez, A. M.; Machado, M. E.; Vilmer, N.; Trottet, G.

1986-01-01

Using the Hard X-ray Imaging Spectrometer (HXIS) from the Solar Maximum Mission Satellite, the morphological aspects and temporal evolution of three major flares which occurred on June 29, 1980 are studied. One of these events, observed at 10:40 UT, is analyzed in particular detail, including Hard X-ray Burst Spectrometer (HXRBS) data and metric wavelength data from the Nancay radioheliograph. The flares occurred during the interaction of two distinct magnetic structures. There is an early onset phase during which there is a weak level of particle acceleration, perhaps accompanied by strong heating within the magnetic interaction region. The impulsive phase of high power energy release is associated with a major interaction between the two structures and accompanied by strong acceleration and heating.

Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease.

PubMed

Frejo, Lidia; Gallego-Martinez, Alvaro; Requena, Teresa; Martin-Sanz, Eduardo; Amor-Dorado, Juan Carlos; Soto-Varela, Andres; Santos-Perez, Sofia; Espinosa-Sanchez, Juan Manuel; Batuecas-Caletrio, Angel; Aran, Ismael; Fraile, Jesus; Rossi-Izquierdo, Marcos; Lopez-Escamez, Jose Antonio

2018-04-13

Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere's disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

PubMed

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

Vega roll and attitude control system algorithms trade-off study

NASA Astrophysics Data System (ADS)

Paulino, N.; Cuciniello, G.; Cruciani, I.; Corraro, F.; Spallotta, D.; Nebula, F.

2013-12-01

This paper describes the trade-off study for the selection of the most suitable algorithms for the Roll and Attitude Control System (RACS) within the FPS-A program, aimed at developing the new Flight Program Software of VEGA Launcher. Two algorithms were analyzed: Switching Lines (SL) and Quaternion Feedback Regulation. Using a development simulation tool that models two critical flight phases (Long Coasting Phase (LCP) and Payload Release (PLR) Phase), both algorithms were assessed with Monte Carlo batch simulations for both of the phases. The statistical outcomes of the results demonstrate a 100 percent success rate for Quaternion Feedback Regulation, and support the choice of this method.

[Application of an artificial neural network in the design of sustained-release dosage forms].

PubMed

Wei, X H; Wu, J J; Liang, W Q

2001-09-01

To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

NASA Astrophysics Data System (ADS)

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

2015-10-01

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.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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03029c

Retrieved Vertical Profiles of Latent Heat Release Using TRMM Rainfall Products

NASA Technical Reports Server (NTRS)

Tao, W.-K.; Lang, S.; Olson, W. S.; Meneghini, R.; Yang, S.; Simpson, J.; Kummerow, C.; Smith, E.

2000-01-01

This paper represents the first attempt to use TRMM rainfall information to estimate the four dimensional latent heating structure over the global tropics for February 1998. The mean latent heating profiles over six oceanic regions (TOGA COARE IFA, Central Pacific, S. Pacific Convergence Zone, East Pacific, Indian Ocean and Atlantic Ocean) and three continental regions (S. America, Central Africa and Australia) are estimated and studied. The heating profiles obtained from the results of diagnostic budget studies over a broad range of geographic locations are used to provide comparisons and indirect validation for the heating algorithm estimated heating profiles. Three different latent heating algorithms, the Goddard Convective-Stratiform (CSH) heating, the Goddard Profiling (GPROF) heating, and the Hydrometeor heating (HH) are used and their results are intercompared. The horizontal distribution or patterns of latent heat release from the three different heating retrieval methods are quite similar. They all can identify the areas of major convective activity (i.e., a well defined ITCZ in the Pacific, a distinct SPCZ) in the global tropics. The magnitude of their estimated latent heating release is also not in bad agreement with each other and with those determined from diagnostic budget studies. However, the major difference among these three heating retrieval algorithms is the altitude of the maximum heating level. The CSH algorithm estimated heating profiles only show one maximum heating level, and the level varies between convective activity from various geographic locations. These features are in good agreement with diagnostic budget studies. By contrast, two maximum heating levels were found using the GPROF heating and HH algorithms. The latent heating profiles estimated from all three methods can not show cooling between active convective events. We also examined the impact of different TMI (Multi-channel Passive Microwave Sensor) and PR (Precipitation Radar) rainfall information on latent heating structures.

Investigating the Origins of Two Extreme Solar Particle Events: Proton Source Profile and Associated Electromagnetic Emissions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kocharov, Leon; Usoskin, Ilya; Pohjolainen, Silja

We analyze the high-energy particle emission from the Sun in two extreme solar particle events in which protons are accelerated to relativistic energies and can cause a significant signal even in the ground-based particle detectors. Analysis of a relativistic proton event is based on modeling of the particle transport and interaction, from a near-Sun source through the solar wind and the Earth’s magnetosphere and atmosphere to a detector on the ground. This allows us to deduce the time profile of the proton source at the Sun and compare it with observed electromagnetic emissions. The 1998 May 2 event is associatedmore » with a flare and a coronal mass ejection (CME), which were well observed by the Nançay Radioheliograph, thus the images of the radio sources are available. For the 2003 November 2 event, the low corona images of the CME liftoff obtained at the Mauna Loa Solar Observatory are available. Those complementary data sets are analyzed jointly with the broadband dynamic radio spectra, EUV images, and other data available for both events. We find a common scenario for both eruptions, including the flare’s dual impulsive phase, the CME-launch-associated decimetric-continuum burst, and the late, low-frequency type III radio bursts at the time of the relativistic proton injection into the interplanetary medium. The analysis supports the idea that the two considered events start with emission of relativistic protons previously accelerated during the flare and CME launch, then trapped in large-scale magnetic loops and later released by the expanding CME.« less

Porewater dynamics of silver, lead and copper in coastal sediments and implications for benthic metal fluxes

USGS Publications Warehouse

Kalnejais, Linda H.; Martin, W. R.; Bothner, Michael H.

2015-01-01

To determine the conditions that lead to a diffusive release of dissolved metals from coastal sediments, porewater profiles of Ag, Cu, and Pb have been collected over seven years at two contrasting coastal sites in Massachusetts, USA. The Hingham Bay (HB) site is a contaminated location in Boston Harbor, while the Massachusetts Bay (MB) site is 11 km offshore and less impacted. At both sites, the biogeochemical cycles include scavenging by Fe-oxyhydroxides and release of dissolved metals when Fe-oxyhydroxides are reduced. Important differences in the metal cycles at the two sites, however, result from different redox conditions. Porewater sulfide and seasonal variation in redox zone depth is observed at HB, but not at MB. In summer, as the conditions become more reducing at HB, trace metals are precipitated as sulfides and are no longer associated with Fe-oxyhydroxides. Sulfide precipitation close to the sediment–water interface limits the trace metal flux in summer and autumn at HB, while in winter, oxidation of the sulfide phases drives high benthic fluxes of Cu and Ag, as oxic conditions return. The annual diffusive flux of Cu at HB is found to be significant and contributes to the higher than expected water column Cu concentrations observed in Boston Harbor. At MB, due to the lower sulfide concentrations, the association of trace metals with Fe-oxyhydroxides occurs throughout the year, leading to more stable fluxes. A surface enrichment of solid phase trace metals was found at MB and is attributed to the persistent scavenging by Fe-oxyhydroxides. This process is important, particularly at sites that are less reducing, because it maintains elevated metal concentrations at the surface despite the effects of bioturbation and sediment accumulation, and because it may increase the persistence of metal contamination in surface sediments.

Hydrogeologic controls on saturation profiles in heat-pipe-like hydrothermal systems: numerical study

NASA Astrophysics Data System (ADS)

Pervin, Mollika; Ghergut, Iulia; Graf, Thomas; Peche, Aaron

2016-04-01

Most geothermal reservoirs are of the liquid-dominated type, and their unexploited-state pressure profile approximately follows the hydrostatic gradient. In very hot liquid-dominated systems, temperature typically follows a boiling-point-for-depth (BPD) relationship. By contrast, vapor-dominated systems exhibit (in their unexploited state) surprisingly small vertical gradients of temperature and pressure, such that a constantly high temperature is encountered over a large vertical thickness, while their pressure approximately follows vapour pressure, pvap(T°). This implies that (Pruess 1985, Truesdell and White 1973): (i) for a vapor-dominated reservoir to exist, it must be sealed laterally - otherwise it would be flooded by neighboring groundwaters with hydrostatic p profile, and (ii) liquid water should somehow be present in the whole system - otherwise p values would not be constrained by the pvap(T°) relationship for water. Historically, one of the most puzzling aspects of vapor-dominated systems was the large amount of heat flowing upwards, while vertical T° gradients remained negligible. This mechanism was deemed as 'heat pipe'(HP) (Eastman 1968): In the central zone of a vapor-dominated system, both vapor and liquid are mobile; vapor flows upwards, condenses at shallower depth, and the liquid condensate flows downwards. Due to the large amount of latent enthalpy released in vapor condensation, the vapor-liquid counter-flow can generate large rates of heat flow with negligible net mass transport (Pruess 1985). In order to be able to exploit two-phase (including vapor-dominated) reservoirs in a sustainable manner, one first needs to understand the conditions under which a two-phase (or a vapor-dominated) system has evolved naturally, and which have led to its present (quasi-) steady undisturbed state. Past studies have found that HP can exist in two distinct states, corresponding to liquid-dominated and vapor-dominated p profiles, respectively. Within this work, we explore some mechanisms and geologic controls that can lead to the formation of extensive vapor-dominated zones within a two-phase system. In particular, we investigate the effect of vertical heterogeneity of permeability (stratified reservoir, containing a permeability barrier) on the liquid water saturation profile within a modified HP model. Though in field observations liquid water has been directly encountered only within the condensation zone at reservoir top, it was speculated that large amounts of liquid water might also exist below the condensation zone. This is of great practical significance to the exploitation of vapor-dominated reservoirs, as their longevity depends on the fluid reserves in place. Within this work, we demonstrate by numerical simulations of a modified HP model that high values of liquid water saturation (>0.8) can prevail even far below the condensation zone. Such findings are useful as a baseline for future calculations regarding the economic exploitation of vapor-dominated systems, where premature productivity drop (or dry-out) is the main issue of concern. References: Eastman, G. Y:, 1968: The heat pipe. Scientific American, 218(5):38-46. Preuss, K. A., 1985: A quantitative model of vapor-dominated geothermal reservoirs as heat pipes in fractured porous rock, Transactions, Geothermal Resources. Council, 9(2), 353-361. Truesdell, A. H., and White, D.E. 1973: Production of superheated Steam from Vapor- dominated geothermal reservoirs. Geothermics, 2(3-4), 154-173

Profile of bovine proteins in retained and normally expelled placenta in dairy cows.

PubMed

Kankofer, M; Wawrzykowski, J; Hoedemaker, M

2014-04-01

Tissue-specific protein profile is determined by its function, structure, intensity of metabolism and usefulness. This profile remains under hormonal control. Any disturbance in the general metabolism may be reflected in changes in both protein quantity and quality. These changes can be of low or high specificity, and some can be used as clinical markers of pathological conditions. The aim of this study was to describe and to compare the protein profile of caruncle and foetal villi of bovine placenta that was either properly released or retained. Placental tissues were collected from healthy cows, divided into releasing and retaining foetal membranes, homogenized and subjected to 1D and 2D electrophoresis. Computer-aided analysis of gel images showed essential qualitative and quantitative alterations in protein profile between tissues that were properly released and retained. Alterations concerned both the number of fractions and spots as well as the intensity of staining. This preliminary study provides a general overview of the differences in the protein profile between released and retained foetal membranes. It may allow for selecting the group of proteins or single molecules, which should be further analysed in detail as possible markers differentiating the retention of foetal membranes in cows from placentas that were released spontaneously. The continuation of the study for the identification of particular spots detected in 2D gels is necessary. © 2013 Blackwell Verlag GmbH.

The release profiles of intact and enzymatically digested hyaluronic acid from semisolid formulations using multi-layer membrane system.

PubMed

Alkrad, Jamal Alyoussef; Mrestani, Yahya; Neubert, Reinhard H H

2003-07-01

A multi-layer membrane system was used to measure in vitro release of hydrophilic macromolecules such as hyaluronic acid (HA) from semisolid formulations. One enzymatically digested HA-derivative with molecular mass of 22 kDa (HA-D) and 1200 kDa intact HA (HA) were incorporated into three semisolid formulations: water-containing hydrophilic ointment (WHO), amphiphilic cream (AC) and water-containing wool wax alcohol ointment (WWO). Because of the high hydrophilic properties of HA-D and HA, the artificial model membranes consisted of collodion as the matrix and glycerol as the hydrophilic acceptor phase. The area under the concentration-time curve and the mean dissolution time were used as a quantitative parameter to characterise the rate and extent of release in vitro. This study showed that the HA-D and HA release as hydrophilic substances from WHO was higher than both from AC and WWO. It was observed that 83% of HA-D1 was released from WHO after 2 h; in contrast, only 10% was released from 2% HA from the same vehicle during the same time. In conclusion, the in vitro availability of enzymatically digested HA-D was higher for WHO than for the other formulations, AC and WWO. Similarly, the availability of HA-D was higher than that of HA from the same formulations.

Hollow microspheres of diclofenac sodium - a gastroretentive controlled delivery system.

PubMed

Bv, Basavaraj; R, Deveswaran; S, Bharath; Abraham, Sindhu; Furtado, Sharon; V, Madhavan

2008-10-01

Most of the floating systems have an inherent drawback of high variability in the GI transit time, invariably affecting the bioavailability of drug. To overcome it, a multiple unit floating system with extended GI transit time, capable of distributing widely throughout the GIT for effective enteric release of the drug has been sought. Microballoons loaded with drug in their outer polymer shells were prepared by novel emulsion solvent diffusion method. The ethanol: dicloromethane solution of drug and Eudragit-S were poured into an aqueous solution of PVA that was thermally controlled at 40 degrees C. The gas phase generated in the dispersed polymer droplet by the evaporation of solvent formed an internal cavity in the microsphere of the polymer with the drug. The flowability of the resulting microballoons improved when compared to pure drug. The microballoons on floatation along with the surfactant, floated continuously for more than 12 hours in the acidic medium in-vitro conditions. The in-vitro drug release profile of the formulation in the simulated gastric buffer showed no drug release, which emphasizes the enteric release property and in simulated intestinal buffer, a slow and controlled drug release of 60 to 84% was obtained over a period of 8 hours. Drug release was significantly affected by increased drug to polymer concentration at pH 6.8. The formulation was found to be physically and chemically stable as per the ICH guidelines.

A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics

NASA Astrophysics Data System (ADS)

Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

2013-01-01

The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca2+ accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics.

PubMed

Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

2013-01-25

The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca(2+) accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

Time dependent chemistry in dense molecular clouds. I - Grain surface reactions, gas/grain interactions and infrared spectroscopy

NASA Technical Reports Server (NTRS)

Dhendecourt, L. B.; Allamandola, L. J.; Greenberg, J. M.

1985-01-01

For the fist time, a time-dependent model is described which includes the role of grains in the production of molecules in dense clouds including ion-molecule gas phase chemistry. The approach provides information regarding the coupling between the two phases. Although the coupling between the two chemistries is extremely strong, the two domains maintain their own identities. While H2O, CH4, and NH3 are made efficiently, with a high production rate on grains and released back to the gas phase, the gas phase is essentially responsible for the formation of CO, a very stable molecule which may or may not react on grains with atomic oxygen and may or may not form CO2.

Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

PubMed

Ye, Guihua; Jiang, Yajun; Yang, Xiaoying; Hu, Hongxiang; Wang, Beibei; Sun, Lu; Yang, Victor C; Sun, Duxin; Gao, Wei

2018-01-10

Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pH e : 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pH endo : 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

PubMed

Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

2016-05-30

The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles

PubMed Central

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J.; Chen, Chih-yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W.; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W.

2016-01-01

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. PMID:26531826

An alternative approach based on artificial neural networks to study controlled drug release.

PubMed

Reis, Marcus A A; Sinisterra, Rubén D; Belchior, Jadson C

2004-02-01

An alternative methodology based on artificial neural networks is proposed to be a complementary tool to other conventional methods to study controlled drug release. Two systems are used to test the approach; namely, hydrocortisone in a biodegradable matrix and rhodium (II) butyrate complexes in a bioceramic matrix. Two well-established mathematical models are used to simulate different release profiles as a function of fundamental properties; namely, diffusion coefficient (D), saturation solubility (C(s)), drug loading (A), and the height of the device (h). The models were tested, and the results show that these fundamental properties can be predicted after learning the experimental or model data for controlled drug release systems. The neural network results obtained after the learning stage can be considered to quantitatively predict ideal experimental conditions. Overall, the proposed methodology was shown to be efficient for ideal experiments, with a relative average error of <1% in both tests. This approach can be useful for the experimental analysis to simulate and design efficient controlled drug-release systems. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Impact of fruit texture on the release and perception of aroma compounds during in vivo consumption using fresh and processed mango fruits.

PubMed

Bonneau, Adeline; Boulanger, Renaud; Lebrun, Marc; Maraval, Isabelle; Valette, Jérémy; Guichard, Élisabeth; Gunata, Ziya

2018-01-15

Two fresh (fresh cubic pieces, fresh puree) and two dried (dried cubic pieces, dried powder) products were prepared from a homogenous mango fruit batch to obtain four samples differing in texture. The aromatic profiles were determined by SAFE extraction technique and GC-MS analysis. VOCs released during consumption were trapped by a retronasal aroma-trapping device (RATD) and analysed by GC-MS. Twenty-one terpenes and one ester were identified from the exhaled nose-space. They were amongst the major mango volatile compounds, 10 of which were already reported as being potential key flavour compounds in mango. The in vivo release of aroma compounds was affected by the matrix texture. The intact samples (fresh and dried cubic pieces) released significantly more aroma compounds than disintegrated samples (fresh puree, dried powder). The sensory descriptive analysis findings were in close agreement with the in vivo aroma release data regarding fresh products, in contrast to the dried products. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geometric flow control of shear bands by suppression of viscous sliding

PubMed Central

Viswanathan, Koushik; Mahato, Anirban; Sundaram, Narayan K.; M'Saoubi, Rachid; Trumble, Kevin P.; Chandrasekar, Srinivasan

2016-01-01

Shear banding is a plastic flow instability with highly undesirable consequences for metals processing. While band characteristics have been well studied, general methods to control shear bands are presently lacking. Here, we use high-speed imaging and micro-marker analysis of flow in cutting to reveal the common fundamental mechanism underlying shear banding in metals. The flow unfolds in two distinct phases: an initiation phase followed by a viscous sliding phase in which most of the straining occurs. We show that the second sliding phase is well described by a simple model of two identical fluids being sheared across their interface. The equivalent shear band viscosity computed by fitting the model to experimental displacement profiles is very close in value to typical liquid metal viscosities. The observation of similar displacement profiles across different metals shows that specific microstructure details do not affect the second phase. This also suggests that the principal role of the initiation phase is to generate a weak interface that is susceptible to localized deformation. Importantly, by constraining the sliding phase, we demonstrate a material-agnostic method—passive geometric flow control—that effects complete band suppression in systems which otherwise fail via shear banding. PMID:27616920

Geometric flow control of shear bands by suppression of viscous sliding

NASA Astrophysics Data System (ADS)

Sagapuram, Dinakar; Viswanathan, Koushik; Mahato, Anirban; Sundaram, Narayan K.; M'Saoubi, Rachid; Trumble, Kevin P.; Chandrasekar, Srinivasan

2016-08-01

Shear banding is a plastic flow instability with highly undesirable consequences for metals processing. While band characteristics have been well studied, general methods to control shear bands are presently lacking. Here, we use high-speed imaging and micro-marker analysis of flow in cutting to reveal the common fundamental mechanism underlying shear banding in metals. The flow unfolds in two distinct phases: an initiation phase followed by a viscous sliding phase in which most of the straining occurs. We show that the second sliding phase is well described by a simple model of two identical fluids being sheared across their interface. The equivalent shear band viscosity computed by fitting the model to experimental displacement profiles is very close in value to typical liquid metal viscosities. The observation of similar displacement profiles across different metals shows that specific microstructure details do not affect the second phase. This also suggests that the principal role of the initiation phase is to generate a weak interface that is susceptible to localized deformation. Importantly, by constraining the sliding phase, we demonstrate a material-agnostic method-passive geometric flow control-that effects complete band suppression in systems which otherwise fail via shear banding.

Comprehensive two-dimensional gas chromatography applied to illicit drug analysis.

PubMed

Mitrevski, Blagoj; Wynne, Paul; Marriott, Philip J

2011-11-01

Multidimensional gas chromatography (MDGC), and especially its latest incarnation--comprehensive two-dimensional gas chromatography (GC × GC)--have proved advantageous over and above classic one-dimensional gas chromatography (1D GC) in many areas of analysis by offering improved peak capacity, often enhanced sensitivity and, especially in the case of GC × GC, the unique feature of 'structured' chromatograms. This article reviews recent advances in MDGC and GC × GC in drug analysis with special focus on ecstasy, heroin and cocaine profiling. Although 1D GC is still the method of choice for drug profiling in most laboratories because of its simplicity and instrument availability, GC × GC is a tempting proposition for this purpose because of its ability to generate a higher net information content. Effluent refocusing due to the modulation (compression) process, combined with the separation on two 'orthogonal' columns, results in more components being well resolved and therefore being analytically and statistically useful to the profile. The spread of the components in the two-dimensional plots is strongly dependent on the extent of retention 'orthogonality' (i.e. the extent to which the two phases possess different or independent retention mechanisms towards sample constituents) between the two columns. The benefits of 'information-driven' drug profiling, where more points of reference are usually required for sample differentiation, are discussed. In addition, several limitations in application of MDGC in drug profiling, including data acquisition rate, column temperature limit, column phase orthogonality and chiral separation, are considered and discussed. Although the review focuses on the articles published in the last decade, a brief chronological preview of the profiling methods used throughout the last three decades is given.

Well logging interpretation of production profile in horizontal oil-water two phase flow pipes

NASA Astrophysics Data System (ADS)

Zhai, Lu-Sheng; Jin, Ning-De; Gao, Zhong-Ke; Zheng, Xi-Ke

2012-03-01

Due to the complicated distribution of local velocity and local phase hold up along the radial direction of pipe in horizontal oil-water two phase flow, it is difficult to measure the total flow rate and phase volume fraction. In this study, we carried out dynamic experiment in horizontal oil-water two phases flow simulation well by using combination measurement system including turbine flowmeter with petal type concentrating diverter, conductance sensor and flowpassing capacitance sensor. According to the response resolution ability of the conductance and capacitance sensor in different range of total flow rate and water-cut, we use drift flux model and statistical model to predict the partial phase flow rate, respectively. The results indicate that the variable coefficient drift flux model can self-adaptively tone the model parameter according to the oil-water two phase flow characteristic, and the prediction result of partial phase flow rate of oil-water two phase flow is of high accuracy.

Effects of mode profile on tunneling and traversal of ultracold atoms through vacuum-induced potentials

NASA Astrophysics Data System (ADS)

Badshah, Fazal; Irfan, Muhammad; Qamar, Sajid; Qamar, Shahid

2016-04-01

We consider the resonant interaction of an ultracold two-level atom with an electromagnetic field inside a high-Q micromaser cavity. In particular, we study the tunneling and traversal of ultracold atoms through vacuum-induced potentials for secant hyperbolic square and sinusoidal cavity mode functions. The phase time which may be considered as an appropriate measure of the time required for the atoms to cross the cavity, significantly modifies with the change of cavity mode profile. For example, switching between the sub and superclassical behaviors in phase time can occur due to the mode function. Similarly, negative phase time appears for the transmission of the two-level atoms in both excited and ground states for secant hyperbolic square mode function which is in contrast to the mesa mode case.

High pressurized CO2 release CFD calculations from onshore pipeline leakages

NASA Astrophysics Data System (ADS)

Herzog, Nicoleta; Gorenz, Paul; Egbers, Christoph

2013-04-01

Emissions from high pressurized pipelines can be determined on the basis of hydrodynamical and thermophysical calculations of the escaped fluid. If a rupture occurs when CO2 is onshore transported in liquid form there will be initially a large pressure drop in the pipeline, the pressure will fall until the liquid becomes a mixture of saturated vapor/liquid. In the vicinity of the rupture, liquid CO2 will escape and immediately vaporize and expand, some of the liquid will desublimate into dry ice, which will precipitate onto the ground [1, 2]. The period of time taken for a large amount of carbon dioxide to be discharged would be short. Initially CO2 will escape by pushing the overlying soil upwards at an explosion-like speed. After the pressure in the pipe fell the flow profile of the escaping gas will almost be as described for gaseous material transport. The expansion of carbon dioxide will occur at sonic speed and will continue to do so until the pressure ratio between the CO2 and the ambient air is lower than about 1.9 [3]. As a result of the expansion also the temperature of the escaping gas will fall drastically and a cloud of cold gas will form which is then dispersed and slowly mixed with ambient air. The rate of emptying the pipeline is controlled by the pipe cross-section area and the speed of the escaping gas, or by the pressure difference between the pipeline and the atmosphere. Therefore the mass flow will be largest immediately after the accident with an exponential decay in time. In this study a two-phase model is applied to a high pressurized pipeline through which liquid carbon dioxide flows. A leakage is considered to be at different positions along the pipeline and the release pressure is calculated over several parameter ranges. It is also intended to characterize from hydrodynamical point of view the dispersion of released CO2 in the ambient medium by means of CFD simulations which includes multiphase flow treatment. For that a turbulent two-phase CFD model is used to analyze the influence of the jet release pressure and leakage dimension on the harmful gaseous CO2 concentration distances. Mazzoldi A., Hill T., Colls J.J.: CO2 transportation for carbon capture and storage: Sublimation of carbon dioxide from a dry ice bank, Int. J. Greenhouse Gas Control, 2, 210-218 (2008) M. Molag, C. Dam: Modelling of accidental releases from a high pressure CO2 pipelines, Energy Procedia, 4, 2301-2307, (2011) Kruse H., Tekiela M.: Calculating the consequences of a CO2-pipeline rupture, Energy Conversion and Management, 37(68), 1013-1018 (1996)

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

PubMed

Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

2001-01-01

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

PubMed

Suarez-Sharp, Sandra; Delvadia, Poonam R; Dorantes, Angelica; Duan, John; Externbrink, Anna; Gao, Zongming; Ghosh, Tapash; Miksinski, Sarah Pope; Seo, Paul

2016-05-01

Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.

Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

PubMed

Lindner, Gabriela da Rocha; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

2015-12-01

Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.

Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.

PubMed

Andhariya, Janki V; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J; Shen, Jie

2017-03-30

The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol ® ) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "real-time" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials.

PubMed

Mitra, Sumita B; Oxman, Joe D; Falsafi, Afshin; Ton, Tiffany T

2011-12-01

To compare the long-term fluoride release kinetics of a novel nano-filled two-paste resin-modified glass-ionomer (RMGI), Ketac Nano (KN) with that of two powder-liquid resin-modified glass-ionomers, Fuji II LC (FLC) and Vitremer (VT) and one conventional glass-ionomer, Fuji IX (FIX). Fluoride release was measured in vitro using ion-selective electrodes. Kinetic analysis was done using regression analysis and compared with existing models for GIs and compomers. In a separate experiment the samples of KN and two conventional glass-ionomers, FIX and Ketac Molar (KM) were subjected to a treatment with external fluoride source (Oral-B Neutra-Foam) after 3 months of fluoride release and the recharge behavior studied for an additional 7-day period. The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P < 0.05. All four materials, including KN, showed a burst of fluoride ions at shorter times (t) and an overall rate dependence on t1/2 typical for glass-ionomers. The coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of swelling and erosion within this matrix at lower fat-wax level which is also supported by release exponent values and Fickian fraction release against time profile of this agent. The results generated in this study showed that proper selection of these hydrophobic materials based on their physico-chemical properties is important in designing wax matrix tablets with desired dissolution profile.

Channel response to sediment release: insights from a paired analysis of dam removal

USGS Publications Warehouse

Collins, Mathias J.; Snyder, Noah P.; Boardman, Graham; Banks, William S.; Andrews, Mary; Baker, Matthew E.; Conlon, Maricate; Gellis, Allen; McClain, Serena; Miller, Andrew; Wilcock, Peter

2017-01-01

Dam removals with unmanaged sediment releases are good opportunities to learn about channel response to abruptly increased bed material supply. Understanding these events is important because they affect aquatic habitats and human uses of floodplains. A longstanding paradigm in geomorphology holds that response rates to landscape disturbance exponentially decay through time. However, a previous study of the Merrimack Village Dam (MVD) removal on the Souhegan River in New Hampshire, USA, showed that an exponential function poorly described the early geomorphic response. Erosion of impounded sediments there was two-phased. We had an opportunity to quantitatively test the two-phase response model proposed for MVD by extending the record there and comparing it with data from the Simkins Dam removal on the Patapsco River in Maryland, USA. The watershed sizes are the same order of magnitude (102 km2), and at both sites low-head dams were removed (~3–4 m) and ~65 000 m3 of sand-sized sediments were discharged to low-gradient reaches. Analyzing four years of repeat morphometry and sediment surveys at the Simkins site, as well as continuous discharge and turbidity data, we observed the two-phase erosion response described for MVD. In the early phase, approximately 50% of the impounded sediment at Simkins was eroded rapidly during modest flows. After incision to base level and widening, a second phase began when further erosion depended on floods large enough to go over bank and access impounded sediments more distant from the newly-formed channel. Fitting functional forms to the data for both sites, we found that two-phase exponential models with changing decay constants fit the erosion data better than single-phase models. Valley width influences the two-phase erosion responses upstream, but downstream responses appear more closely related to local gradient, sediment re-supply from the upstream impoundments, and base flows.

Be discs in coplanar circular binaries: Phase-locked variations of emission lines

NASA Astrophysics Data System (ADS)

Panoglou, Despina; Faes, Daniel M.; Carciofi, Alex C.; Okazaki, Atsuo T.; Baade, Dietrich; Rivinius, Thomas; Borges Fernandes, Marcelo

2018-01-01

In this paper, we present the first results of radiative transfer calculations on decretion discs of binary Be stars. A smoothed particle hydrodynamics code computes the structure of Be discs in coplanar circular binary systems for a range of orbital and disc parameters. The resulting disc configuration consists of two spiral arms, and this can be given as input into a Monte Carlo code, which calculates the radiative transfer along the line of sight for various observational coordinates. Making use of the property of steady disc structure in coplanar circular binaries, observables are computed as functions of the orbital phase. Some orbital-phase series of line profiles are given for selected parameter sets under various viewing angles, to allow comparison with observations. Flat-topped profiles with and without superimposed multiple structures are reproduced, showing, for example, that triple-peaked profiles do not have to be necessarily associated with warped discs and misaligned binaries. It is demonstrated that binary tidal effects give rise to phase-locked variability of the violet-to-red (V/R) ratio of hydrogen emission lines. The V/R ratio exhibits two maxima per cycle; in certain cases those maxima are equal, leading to a clear new V/R cycle every half orbital period. This study opens a way to identifying binaries and to constraining the parameters of binary systems that exhibit phase-locked variations induced by tidal interaction with a companion star.

Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals-an In Vitro and In Vivo Evaluation.

PubMed

Biswas, Nikhil; Kuotsu, Ketousetuo

2017-02-01

The objective was to improve the dissolution of valsartan by developing valsartan nanocrystals and design a pulsed release system for the chronotherapy of hypertension. Valsartan nanocrystals were prepared by sonication-anti-solvent precipitation method and lyophilized to obtain dry powder. Nanocrystals were directly compressed to minitablets and coated to achieve pulsatile valsartan release. Pharmacokinetic profiles of optimized and commercial formulations were compared in rabbit model. The mean particle size and PDI of the optimized nanocrystal batch V4 was reported as 211 nm and 0.117, respectively. DSC and PXRD analysis confirmed the crystalline nature of valsartan in nanocrystals. The dissolution extent of valsartan was markedly enhanced with both nanocrystals and minitablets as compared to pure valsartan irrespective of pH of the medium. Core minitablet V4F containing 5% w/w polyplasdone XL showed quickest release of valsartan, over 90% within 15 min. Coated formulation CV4F showed two spikes in release profile after successive lag times of 235 and 390 min. The pharmacokinetic study revealed that the bioavailability of optimized formulation (72.90%) was significantly higher than the commercial Diovan tablet (30.18%). The accelerated stability studies showed no significant changes in physicochemical properties, release behavior, and bioavialability of CV4F formulation. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.

Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler.

PubMed

Tagami, Tatsuaki; Nagata, Noriko; Hayashi, Naomi; Ogawa, Emi; Fukushige, Kaori; Sakai, Norihito; Ozeki, Tetsuya

2018-05-30

3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers. Copyright © 2018 Elsevier B.V. All rights reserved.

Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells.

PubMed

Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

2014-01-01

We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues.

Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells

PubMed Central

Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

2014-01-01

We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues. PMID:25429215

Eddy Seeding in the Labrador Sea: a Submerged Autonomous Launching Platform (SALP) Application

NASA Astrophysics Data System (ADS)

Furey, Heather H.; Femke de Jong, M.; Bower, Amy S.

2013-04-01

A simplified Submerged Autonomous Launch Platform (SALP) was used to release profiling floats into warm-core Irminger Rings (IRs) in order to investigate their vertical structure and evolution in the Labrador Sea from September 2007 - September 2009. IRs are thought to play an important role in restratification after convection in the Labrador Sea. The SALP is designed to release surface drifters or subsurface floats serially from a traditional ocean mooring, using real-time ocean measurements as criteria for launch. The original prototype instrument used properties measured at multiple depths, with information relayed to the SALP controller via acoustic modems. In our application, two SALP carousels were attached at 500 meters onto a heavily-instrumented deep water mooring, in the path of recently-shed IRs off the west Greenland shelf. A release algorithm was designed to use temperature and pressure measured at the SALP depth only to release one or two APEX profiling drifters each time an IR passed the mooring, using limited historical observations to set release thresholds. Mechanically and electronically, the SALP worked well: out of eleven releases, there was only one malfunction when a float was caught in the cage after the burn-wire had triggered. However, getting floats trapped in eddies met with limited success due to problems with the release algorithm and float ballasting. Out of seven floats launched from the platform using oceanographic criteria, four were released during warm water events that were not related to passing IRs. Also, after float release, it took on average about 2.6 days for the APEX to adjust from its initial ballast depth, about 600 meters, to its park point of 300 meters, leaving the float below the trapped core of water in the IRs. The other mooring instruments (at depths of 100 to 3000 m), revealed that 12 IRs passed by the mooring in the 2-year monitoring period. With this independent information, we were able to assess and improve the release algorithm, still based on ocean conditions measured only at one depth. We found that much better performance could have been achieved with an algorithm that detected IRs based on a temperature difference from a long-term running mean rather than a fixed temperature threshold. This highlights the challenge of designing an appropriate release strategy with limited a priori information on the amplitude and time scales of the background variability.

Effects of a Physical Exercise Program (PEP-Aut) on Autistic Children's Stereotyped Behavior, Metabolic and Physical Activity Profiles, Physical Fitness, and Health-Related Quality of Life: A Study Protocol.

PubMed

Ferreira, José Pedro; Andrade Toscano, Chrystiane Vasconcelos; Rodrigues, Aristides Machado; Furtado, Guilherme Eustaquio; Barros, Mauro Gomes; Wanderley, Rildo Souza; Carvalho, Humberto Moreira

2018-01-01

Physical exercise has shown positive effects on symptomatology and on the reduction of comorbidities in population with autism spectrum disorder (ASD). However, there is still no consensus about the most appropriate exercise intervention model for children with ASD. The physical exercise program for children with autism (PEP-Aut) protocol designed allow us to (i) examine the multivariate associations between ASD symptoms, metabolic profile, physical activity level, physical fitness, and health-related quality of life of children with ASD; (ii) assess the effects of a 40-week exercise program on all these aspects of children with ASD. The impact of the exercise program will be assessed based on the sequence of the two phases. Phase 1 is a 12-week cross-sectional study assessing the symptomatology, metabolic profile, physical fitness and physical activity levels, socioeconomic status profile, and health-related quality of life of participants. This phase is the baseline of the following phase. Phase 2 is a 48-week intervention study with a 40-week intervention with exercise that will take place in a specialized center for children with ASD in the city of Maceió-Alagoas, Brazil. The primary outcomes will be change in the symptomatic profile and the level of physical activity of children. Secondary outcomes will be anthropometric and metabolic profiles, aerobic function, grip strength, socioeconomic status, and health-related quality of life. The study will provide critical information on the efficacy of exercise for children with ASD and help guide design and delivery of future programs.

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo)

PubMed Central

Moeller, John F.; Meredith, Michael

2010-01-01

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RFamide-like peptides. To define further the cell populations and connectivity, we used double-label immuno-cytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH immunoreactive (ir) cell-profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies, and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT) negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. PMID:20950589

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

PubMed

Moeller, John F; Meredith, Michael

2010-12-17

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

Distinguishing splanchnic nerve and chromaffin cell stimulation in mouse adrenal slices with fast-scan cyclic voltammetry

PubMed Central

Walsh, Paul L.; Petrovic, Jelena

2011-01-01

Electrical stimulation is an indispensible tool in studying electrically excitable tissues in neurobiology and neuroendocrinology. In this work, the consequences of high-intensity electrical stimulation on the release of catecholamines from adrenal gland slices were examined with fast-scan cyclic voltammetry at carbon fiber microelectrodes. A biphasic signal, consisting of a fast and slow phase, was observed when electrical stimulations typically used in tissue slices (10 Hz, 350 μA biphasic, 2.0 ms/phase pulse width) were applied to bipolar tungsten-stimulating electrodes. This signal was found to be stimulation dependent, and the slow phase of the signal was abolished when smaller (≤250 μA) and shorter (1 ms/phase) stimulations were used. The slow phase of the biphasic signal was found to be tetrodotoxin and hexamethonium independent, while the fast phase was greatly reduced using these pharmacological agents. Two different types of calcium responses were observed, where the fast phase was abolished by perfusion with a low-calcium buffer while both the fast and slow phases could be modulated when Ca2+ was completely excluded from the solution using EGTA. Perfusion with nifedipine resulted in the reduction of the slow catecholamine release to 29% of the original signal, while the fast phase was only decreased to 74% of predrug values. From these results, it was determined that high-intensity stimulations of the adrenal medulla result in depolarizing not only the splanchnic nerves, but also the chromaffin cells themselves resulting in a biphasic catecholamine release. PMID:21048165

Roughness exponent in two-dimensional percolation, Potts model, and clock model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redinz, Jose Arnaldo; Martins, Marcelo Lobato

We present a numerical study of the self-affine profiles obtained from configurations of the q-state Potts (with q=2,3, and 7) and p=10 clock models as well as from the occupation states for site percolation on the square lattice. The first and second order static phase transitions of the Potts model are located by a sharp change in the value of the roughness exponent {alpha} characterizing those profiles. The low temperature phase of the Potts model corresponds to flat ({alpha}{approx_equal}1) profiles, whereas its high temperature phase is associated with rough ({alpha}{approx_equal}0.5) ones. For the p=10 clock model, in addition to themore » flat (ferromagnetic) and rough (paramagnetic) profiles, an intermediate rough (0.5{lt}{alpha}{lt}1) phase{emdash}associated with a soft spin-wave one{emdash}is observed. Our results for the transition temperatures in the Potts and clock models are in agreement with the static values, showing that this approach is able to detect the phase transitions in these models directly from the spin configurations, without any reference to thermodynamical potentials, order parameters, or response functions. Finally, we show that the roughness exponent {alpha} is insensitive to geometric critical phenomena.« less

Spin-Imbalanced Quasi-Two-Dimensional Fermi Gases

NASA Astrophysics Data System (ADS)

Ong, W.; Cheng, Chingyun; Arakelyan, I.; Thomas, J. E.

2015-03-01

We measure the density profiles for a Fermi gas of Li 6 containing N1 spin-up atoms and N2 spin-down atoms, confined in a quasi-two-dimensional geometry. The spatial profiles are measured as a function of spin imbalance N2/N1 and interaction strength, which is controlled by means of a collisional (Feshbach) resonance. The measured cloud radii and central densities are in disagreement with mean-field Bardeen-Cooper-Schrieffer theory for a true two-dimensional system. We find that the data for normal-fluid mixtures are reasonably well fit by a simple two-dimensional polaron model of the free energy. Not predicted by the model is a phase transition to a spin-balanced central core, which is observed above a critical value of N2/N1. Our observations provide important benchmarks for predictions of the phase structure of quasi-two-dimensional Fermi gases.

Monte Carlo simulation of single accident airport risk profile

NASA Technical Reports Server (NTRS)

1979-01-01

A computer simulation model was developed for estimating the potential economic impacts of a carbon fiber release upon facilities within an 80 kilometer radius of a major airport. The model simulated the possible range of release conditions and the resulting dispersion of the carbon fibers. Each iteration of the model generated a specific release scenario, which would cause a specific amount of dollar loss to the surrounding community. By repeated iterations, a risk profile was generated, showing the probability distribution of losses from one accident. Using accident probability estimates, the risks profile for annual losses was derived. The mechanics are described of the simulation model, the required input data, and the risk profiles generated for the 26 large hub airports.

Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.

PubMed

Liu, Hongzhuo; Shang, Kuimao; Liu, Weina; Leng, Donglei; Li, Ran; Kong, Ying; Zhang, Tianhong

2014-01-01

The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.

Ondansetron Suppositories: Extemporaneous Preparation, Drug Release, Stability and Flux through Rabbit Rectal Membrane.

PubMed

Tenjarla, S N; Ward, E S; Fox, J L

1998-01-01

The objective of this study was to determine the feasibility and develop a formulation for an extemporaneously prepared ondansetron suppository form Zofran 8-mg tablets. The stability of the formulation over 28 days of refrigerated storage and the initial and poststorage drug-release profiles were evaluated. The ondansetron flux in an in vitro model (a rabbit rectal membrane) from each formulation was determined. Suppositories containing 8 or 16 mg ondansetron were made using commercially available hydrophobic and hydrophilic suppository bases. A sensitive, stability-indication high-performance liquid chromatography assay was used for the analysis of ondansetron. The partition coefficient (octanol/water) of ondansetron and the displacement factor of tablets with each of the two bases were determined . The suppositories, formed in disposable molds, were kept in plastic wwrap and stored at 5 deg C in the refrigerator. The effect of storage on ondansetron release from the suppository base and the stability of ondansetron in the two suppository bases were evaluated over a period of 28 days. The dissolution study provided data on the release profile of the drug over 28 days, as well as the stabilty of the drug during the storage period. Ondansetron flux through rabbit rectal membrane from the various formulations was determined in vitro using modified Franz diffusion cells. Greater than 90% of the intiial amount (8 or 16 mg) of ondansetron was retained in the suppositories after 28-day storage at 5 deg C for both hydrophilic and hydrophobic formulations. There was no statistically siginificant difference in the drug-release profiles during this period. Ondansetron flux through the rabbit rectal membrane from 8- and 16-mg hydrophobic suppositories was 393 +/- 58 and 76.2 +/- 13.8 micrograms per centimeters squared -hour, respectively (n=6). The corresponding flux from 8- and 16-mg hydrophilic suppositories was 37.8 +/- 16 and 81.7 +/- 22.9 micrograms per centimeter squared - hour, respectively. The variablility in the flux required further study but the levels achieved indicated that extemporaneous preparation of ondansetron suppositories is reasonable using commercially available components.

PEGylated lipid nanocapsules with improved drug encapsulation and controlled release properties.

PubMed

Hervella, Pablo; Alonso-Sande, Maria; Ledo, Francisco; Lucero, Maria L; Alonso, Maria J; Garcia-Fuentes, Marcos

2014-01-01

Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol(®), lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy.

The intra-push velocity profile of the over-ground racing wheelchair sprint start.

PubMed

Moss, A D; Fowler, N E; Goosey-Tolfrey, V L

2005-01-01

The aim of this study was to analyse the first six pushes of a sprint start in over-ground racing wheelchair propulsion. One international male wheelchair athlete (age=28 years; body mass=60.6 kg; racing classification=T4) performed maximal over-ground sprint trials, over approximately 10 m, in his own racing wheelchair fitted with a velocometer. Each trial was filmed at 200 Hz using a "Pan and Tilt" system. Eight trials were manually digitised at 100 Hz. Raw co-ordinate data were smoothed and differentiated using a quintic spline routine. Across the period from pushes one to six the duration of each push cycle decreased (0.82+/-0.02-0.45+/-0.01 s) with the mean duration of the propulsive phase decreasing from 0.62+/-0.02 to 0.21+/-0.01 s and the recovery phase increasing from 0.20+/-0.01 to 0.24+/-0.02 s. The push-rim was contacted progressively closer to top dead centre and released progressively closer to bottom dead centre with each push. The data indicate that peak velocity occurred after release. The main findings of this study support the observation that racing wheelchair sprint propulsion is a complex form of locomotion and cannot be described accurately by using just the established definitions of a propulsive and a recovery phase.

Multi-foci metalens for spin and orbital angular momentum interaction

NASA Astrophysics Data System (ADS)

Mei, Shengtao; Mehmood, M. Q.; Huang, Kun; Qiu, Cheng-Wei

2015-09-01

The development of metasurface, capable of controlling wave-fronts through interfacial phase discontinuity, offers a fascinating methodology for designing two dimensional miniaturized optical devices. Owing to an additional advantage of the enhanced useful transmission via Bainet-inverted matasurface, we exploit them to demonstrate an intriguing concept of merging the phase-profiles of two distinct optical devices, a lens and a spiral phase plate, to realize an ultrathin nanostructured optical vortex lens. The proposed device can has multiple focal planes along the longitudinal direction; whereas the number of focal plans, corresponding topological charges and focal lengths can readily be tailored to meet any desired requirements. Meanwhile, the dual-polarity feature of the optical vertex metalens exhibits spin controlled real and virtual focal plans, while dispersionless aptitude of nanobars enables its working over the broadband. The concept unveils a novel way of employing metasurface, to engraft the phase profiles of multiple bulk devices, to achieve unique functionalities for promising applications in integrated photonics.

Mechanical breath profile of airway pressure release ventilation: the effect on alveolar recruitment and microstrain in acute lung injury.

PubMed

Kollisch-Singule, Michaela; Emr, Bryanna; Smith, Bradford; Roy, Shreyas; Jain, Sumeet; Satalin, Joshua; Snyder, Kathy; Andrews, Penny; Habashi, Nader; Bates, Jason; Marx, William; Nieman, Gary; Gatto, Louis A

2014-11-01

Improper mechanical ventilation settings can exacerbate acute lung injury by causing a secondary ventilator-induced lung injury. It is therefore important to establish the mechanism by which the ventilator induces lung injury to develop protective ventilation strategies. It has been postulated that the mechanism of ventilator-induced lung injury is the result of heterogeneous, elevated strain on the pulmonary parenchyma. Acute lung injury has been associated with increases in whole-lung macrostrain, which is correlated with increased pathology. However, the effect of mechanical ventilation on alveolar microstrain remains unknown. To examine whether the mechanical breath profile of airway pressure release ventilation (APRV), consisting of a prolonged pressure-time profile and brief expiratory release phase, reduces microstrain. In a randomized, nonblinded laboratory animal study, rats were randomized into a controlled mandatory ventilation group (n = 3) and an APRV group (n = 3). Lung injury was induced by polysorbate lavage. A thoracotomy was performed and an in vivo microscope was placed on the lungs to measure alveolar mechanics. In the controlled mandatory ventilation group, multiple levels of positive end-expiratory pressure (PEEP; 5, 10, 16, 20, and 24 cm H2O) were tested. In the APRV group, decreasing durations of expiratory release (time at low pressure [T(low)]) were tested. The T(low) was set to achieve ratios of termination of peak expiratory flow rate (T-PEFR) to peak expiratory flow rate (PEFR) of 10%, 25%, 50%, and 75% (the smaller this ratio is [ie, 10%], the more time the lung is exposed to low pressure during the release phase, which decreases end-expiratory lung volume and potentiates derecruitment). Alveolar perimeters were measured at peak inspiration and end expiration using digital image analysis, and strain was calculated by normalizing the change in alveolar perimeter length to the original length. Macrostrain was measured by volume displacement. Higher PEEP (16-24 cm H2O) and a brief T(low) (APRV T-PEFR to PEFR ratio of 75%) reduced microstrain. Microstrain was minimized with an APRV T-PEFR to PEFR ratio of 75% (mean [SEM], 0.05 [0.03]) and PEEP of 16 cm H2O (mean [SEM], 0.09 [0.08]), but an APRV T-PEFR to PEFR ratio of 75% also promoted alveolar recruitment compared with PEEP of 16 cm H2O (mean [SEM] total inspiratory area, 52.0% [2.9%] vs 29.4% [4.3%], respectively; P < .05). Whole-lung strain was correlated with alveolar microstrain in tested settings (P < .05) except PEEP of 16 cm H2O (P > .05). Increased positive-end expiratory pressure and reduced time at low pressure (decreased T(low)) reduced alveolar microstrain. Reduced microstrain and improved alveolar recruitment using an APRV T-PEFR to PEFR ratio of 75% may be the mechanism of lung protection seen in previous clinical and animal studies.

Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets.

PubMed

Martínez-González, Ilona; Villafuerte-Robles, Leopoldo

2004-01-01

A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes.

Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

PubMed

Kenawy, El-Refaie; Bowlin, Gary L; Mansfield, Kevin; Layman, John; Simpson, David G; Sanders, Elliot H; Wnek, Gary E

2002-05-17

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

Effect of mean diameter and polydispersity of PLG microspheres on drug release: experiment and theory.

PubMed

Berchane, N S; Carson, K H; Rice-Ficht, A C; Andrews, M J

2007-06-07

The need to tailor release rate profiles from polymeric microspheres is a significant problem. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In this work the effects of microspheres mean diameter, polydispersity, and polymer degradation on drug release rate from poly(lactide-co-glycolide) (PLG) microspheres are described. Piroxicam containing PLG microspheres were fabricated at 20% loading, and at three different impeller speeds. A portion of the microspheres was then sieved giving five different size distributions. In vitro release kinetics were determined for each preparation. Based on these experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. For highly polydisperse populations (polydispersity parameter b<3), incorporating the microsphere size distribution into the mathematical model gave a better fit to the experimental results than using the representative mean diameter. The validated mathematical model can be used to predict small-molecule drug release from PLG microsphere populations.

Analysis of grating doublets for achromatic beam-splitting

PubMed Central

Pacheco, Shaun; Milster, Tom; Liang, Rongguang

2015-01-01

Achromatic beam-splitting grating doublets are designed for both continuous phase and binary phase gratings. By analyzing the sensitivity to lateral shifts between the two grating layers, it is shown that continuous-profile grating doublets are extremely difficult to fabricate. Achromatic grating doublets that have profiles with a constant first spatial derivative are significantly more resistant to lateral shifts between grating layers, where one design case showed a 17 times improvement in performance. Therefore, binary phase, multi-level phase, and blazed grating doublets perform significantly better than continuous phase grating doublets in the presence of a lateral shift between two grating layers. By studying the sensitivity to fabrication errors in the height of both grating layers, one grating layer height can be adjusted to maintain excellent performance over a large wavelength range if the other grating layer is fabricated incorrectly. It is shown in one design case that the performance of an achromatic Dammann grating doublet can be improved by a factor of 215 if the heights of the grating layers are chosen to minimize the performance change in the presence of fabrication errors. PMID:26368261

From solid to liquid: Assessing the release of carbon from soil into solution in response to forest management

NASA Astrophysics Data System (ADS)

James, J. N.; Gross, C. D.; Butman, D. E.; Harrison, R. B.

2016-12-01

Dissolved organic matter (DOM) is a crucial conduit for internal cycling of carbon within soils as well as for the transfer of organic matter out of soil and into aquatic systems. Little is known about how the quantity, quality, lability and chemical characteristics of DOM changes in response to human management of forest soils. To examine the processes that release soil organic matter (SOM) into solution, we gathered samples from adjacent native and industrially managed Eucalyptus grandis plantation forests across Sao Paulo State, Brazil and from adjacent old-growth and Douglas-fir (Pseudotsuga menzisii) plantation forests in the coastal Pacific Northwest. Samples from each soil horizon were taken from soil profiles excavated to at least 1.5 m at each site. Water extractable organic matter (WEOM) was extracted twice from each sample using 0.5 M K2SO4 and Milli-Q water to quantify both dissolved and exchange phase organic matter. These extracts were measured for total organic carbon (TOC), 13C and 14C, and chemical characteristics were assessed by fluorescence spectroscopy (EEMs and SUVA254). At the same time, solid phase characteristics of the soil samples were quantified, including bulk density, pH, total carbon and nitrogen, microbial biomass, and 13C and 14C. Characterization of bulk SOM was undertaken by Fourier Transform Infrared Spectroscopy (FTIR) by subtracting mineral matrix spectra of each sample from the bulk spectra. Organic matter lability was assessed by incubations using difference in TOC for WEOM extracts and repeated measurement of CO2 efflux for bulk SOM. All together, these analyses permit a unique snapshot of the natural separation of organic matter from solid into liquid phase through the entire soil profile. Initial results reveal that small but measureable quantities of WEOM may be released from deep B and C horizons in soil, and that this material is labile to microbial decomposition. By identifying differences in SOM and DOM cycling due to forest management, this study aims to connect human management of terrestrial forest ecosystems to the transport of organic matter from surface and subsurface horizons to freshwater ecosystems, where it forms a major component of aquatic food webs.

Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

PubMed

Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

2007-07-18

Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

Release of indomethacin from ultrasound dry granules containing lactose-based excipients.

PubMed

Cavallari, Cristina; Albertini, Beatrice; Rodriguez, Lorenzo; Rabasco, Antonio M; Fini, Adamo

2005-01-20

Physical mixtures were prepared containing indomethacin and beta-lactose and alpha-lactose-based excipients (Ludipress and Cellactose). The mixtures were compacted with the aid of ultrasound, obtaining tablets, which were milled and sieved. Granules thus obtained were examined by optical microscopy and differential scanning calorimetry. The intense yellow color of the granules and the absence of indomethacin peak in thermograms suggest important modifications of indomethacin physical state; the drug thus modified appears to be spread on the excipient particle surface as a thin film, giving a lustrous appearance. No influence of ultrasound was observed on phase transition concerning lactose; only loss of water was important under high energy ultrasound. Dissolution profiles suggest an increased release of the drug from the systems treated with ultrasound at high energy, with respect to a traditional compaction; while no difference could be evidenced among the three excipients that, however, appear all suitable for this ultrasound-aided direct compression process.

Design and in vitro evaluation of a new nano-microparticulate system for enhanced aqueous-phase solubility of curcumin.

PubMed

Guzman-Villanueva, Diana; El-Sherbiny, Ibrahim M; Herrera-Ruiz, Dea; Smyth, Hugh D C

2013-01-01

Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-microparticulate systems are based entirely on biocompatible, biodegradable, and edible polymers including chitosan, alginate, and carrageenan. The particles were synthesized via ionotropic gelation. Encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin. Also, the in vitro release profile showed up to 95% release of curcumin from the developed nano-microparticulate systems after 9 hours in PBS at pH 7.4 when freeze-dried particles were used.

Combustion diagnostic for active engine feedback control

DOEpatents

Green, Jr., Johney Boyd; Daw, Charles Stuart; Wagner, Robert Milton

2007-10-02

This invention detects the crank angle location where combustion switches from premixed to diffusion, referred to as the transition index, and uses that location to define integration limits that measure the portions of heat released during the combustion process that occur during the premixed and diffusion phases. Those integrated premixed and diffusion values are used to develop a metric referred to as the combustion index. The combustion index is defined as the integrated diffusion contribution divided by the integrated premixed contribution. As the EGR rate is increased enough to enter the low temperature combustion regime, PM emissions decrease because more of the combustion process is occurring over the premixed portion of the heat release rate profile and the diffusion portion has been significantly reduced. This information is used to detect when the engine is or is not operating in a low temperature combustion mode and provides that feedback to an engine control algorithm.

Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-01-01

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

A two-step method for retrieving the longitudinal profile of an electron bunch from its coherent radiation

NASA Astrophysics Data System (ADS)

Pelliccia, Daniele; Sen, Tanaji

2014-11-01

The coherent radiation emitted by an electron bunch provides a diagnostic signal that can be used to estimate its longitudinal distribution. Commonly only the amplitude of the intensity spectrum can be measured and the associated phase must be calculated to obtain the bunch profile. Very recently an iterative method was proposed to retrieve this phase. However ambiguities associated with non-uniqueness of the solution are always present in the phase retrieval procedure. Here we present a method to overcome the ambiguity problem by first performing multiple independent runs of the phase retrieval procedure and then second, sorting the good solutions by means of cross-correlation analysis. Results obtained with simulated bunches of various shapes and experimental measured spectra are presented, discussed and compared with the established Kramers-Kronig method. It is shown that even when the effect of the ambiguities is strong, as is the case for a double peak in the profile, the cross-correlation post-processing is able to filter out unwanted solutions. We show that, unlike the Kramers-Kronig method, the combined approach presented is able to faithfully reconstruct complicated bunch profiles.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

PubMed Central

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200 mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin

PubMed Central

Li, Xiaomeng; Qin, Jinli; Ma, Jun

2015-01-01

A silk fibroin/poly (vinyl alcohol) porous scaffold with a water vapor transmission rate of 2125 ± 464 g/m2/day has been developed via thermally induced phase separation (gelation) and freeze-drying process. A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds, and the related structures were analyzed. The viability and proliferation of 3T3 fibroblasts were examined, which indicated that the scaffolds exerted low cytotoxicity. After loading curcumin, the scaffolds can suppress the growth of 3T3 fibroblasts. The release behavior of curcumin from the scaffolds was investigated. At pH = 7.2, the release profiles showed no significant difference for the loading amounts of 0.5 mg and 0.25 mg per sample. Meanwhile, the cumulative amount of released drug at pH = 5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds. It was suggested that the silk fibroin/poly (vinyl alcohol) blend scaffolds could be potentially used as wound dressing materials. PMID:26816634

Effect of sodium tripolyphosphate concentration and simulated gastrointestinal fluids on release profile of paracetamol from chitosan microsphere

NASA Astrophysics Data System (ADS)

Mulia, Kamarza; Andrie; Krisanti, Elsa A.

2018-03-01

The problem to overcome in oral drug administration is the significant pH changes present in the human digestive system. In this study, ionotropic gelation method employing 2-8% (w/v) tripolyphosphate solutions were used to crosslink chitosan microspheres for a controlled release of paracetamol as a model drug. The release profiles of paracetamol from chitosan microspheres were determined using simulated gastrointestinal fluids having pH values of 1.2, 6.8, and 7.4. The results showed that the paracetamol loading and the encapsulation efficiency values increased with increasing concentration of tripolyphosphate solutions used in the preparation step. Paracetamol released at pH 1.2 and 6.8 buffer solutions was significantly higher than that at pH 7.4; also, more paracetamol was released in the presence of α-amylase and β-glucosidase enzymes. The release profiles showed zero-order release behaviour up to 8 hours where the highest drug release was 39% of the paracetamol loaded in the chitosan microspheres, indicating a strong crosslinking between chitosan and TPP anions. The relatively low accumulated drug release could be compensated by employing suitable enzymes, lower TPP solution concentration, and addition of other biodegradable polymer to reduce the TPP crosslink.

Effect of sequential release of NAPLs on NAPL migration in porous media

NASA Astrophysics Data System (ADS)

Bang, Woohui; Yeo, In Wook

2016-04-01

NAPLs (Non-aqueous phase liquids) are common groundwater contaminants and are classified as LNAPLs (Light non-aqueous phase liquids) and DNAPLs (Dense non-aqueous phase liquids) according to relative density for water. Due to their low solubility in water, NAPLs remain for a long time in groundwater, and they pose a serious environmental problem. Therefore, understanding NAPLs migration in porous media is essential for effective NAPLs remediation. DNAPLs tend to move downward through the water table by gravity force because its density is higher than water. However, if DNAPLs do not have sufficient energy which breaks capillary force of porous media, they will just accumulate above capillary zone or water table. Mobile phase of LNAPLs rises and falls depending on fluctuation of water table, and it could change the wettability of porous media from hydrophilic to hydrophobic. This could impacts on the migration characteristics of subsequently-released DNAPLs. LNAPLs and DNAPLs are sometime disposed at the same place (for example, the Hill air force base, USA). Therefore, this study focuses on the effect of sequential release of NAPLs on NAPLs (in particular, DNAPL) migration in porous media. We have conducted laboratory experiments. Gasoline, which is known to change wettability of porous media from hydrophilic to intermediate, and TCE (Trichloroethylene) were used as LNAPL and DNAPL, respectively. Glass beads with the grain size of 1 mm and 2 mm were prepared for two sets of porous media. Gasoline and TCE was dyed for visualization. First, respective LNAPL and DNAPL of 10 ml were separately released into prepared porous media. For the grain size of 2 mm glass beads, LNAPL became buoyant above the water table, and DNAPL just moved downward through porous media. However, for the experiment with the grain size of 1 mm glass beads, NAPLs behaved very differently. DNAPL did not migrate downward below and just remained above the water table due to capillary pressure of porous media. To study the effect of subsequent release of NAPLs, as soon as LNAPL was released to porous medium with 1 mm of glass beads, being buoyant above water table, water table was lowered, which left residuals along the path of LNAPL. DNAPL was subsequently released. DNAPL was breaking through the water table now, which was opposed to only DNAPL release case. This study indicates that sequential release of NAPLs can leads to different migration characteristics of NAPLs, compared with the release of single phase NAPL into porous media.

Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation.

PubMed

Han, Dehui; Tong, Xia; Zhao, Yue

2012-02-07

We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

PubMed Central

Severino, Patrícia; de Oliveira, George G.G.; Ferraz, Humberto G.; Souto, Eliana B.; Santana, Maria H.A.

2012-01-01

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration, aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile. Chitosan microspheres were produced under fluidized bed, followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm. The pellets were then coated with Kollidon® VA64 and Kollicoat® MAE100P in water dispersion to depict a sustained release profile. Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine. Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine. PMID:29403741

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles.

PubMed

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J; Chen, Chih-Yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W

2016-01-04

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

An assessment of detection canine alerts using flowers that release methyl benzoate, the cocaine odorant, and an evaluation of their behavior in terms of the VOCs produced.

PubMed

Cerreta, Michelle M; Furton, Kenneth G

2015-06-01

In recent years, the high frequency of illicit substance abuse reported in the United States has made the development of efficient and rapid detection methods important. Biological detectors, such as canines (Canis familiaris), are valuable tools for rapid, on-site identification of illicit substances. However, research indicates that in many cases canines do not alert to the contraband, but rather to the volatile organic compounds (VOCs) that are released from the contraband, referred to as the "active odor." In 2013, canine accuracy and reliability were challenged in the Supreme Court case, State of Florida v. Jardines. In this case, it was stated that if a canine alerts to the active odor, and not the contraband, the canine's accuracy and selectivity could be questioned, since many of these compounds have been found in common household products. Specifically, methyl benzoate, the active odor of cocaine, has been found to be the most abundant compound produced by snapdragon flowers. Therefore, the purpose of this study is to evaluate the odor profiles of various species of snapdragon flowers to assess how significantly methyl benzoate contributes to the total VOC profile or fragrance that is produced. Particularly, this study examines the VOCs released from newly grown snapdragon flowers and determines its potential at eliciting a false alert from specially trained detection canines. The ability of detection canines to differentiate between cocaine and snapdragon flowers was determined in order to validate the field accuracy and discrimination power of these detectors. An optimized method using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS) was used to test the different types and abundances of compounds generated from snapdragon flowers at various stages throughout the plants' life cycle. The results indicate that although methyl benzoate is present in the odor profile of snapdragon flowers, other compounds are present that contribute significantly, if not more, than that of methyl benzoate. Canine teams, from various police departments throughout South Florida, certified for narcotics detection, took part in this study. Two canine trials involving 21 canines teams were performed by exposing the teams to 4 different species of snapdragon flowers. Of the 21 canine teams tested, none alerted to the snapdragon flowers presented, while all (100%) alerted to real cocaine samples, the positive control. Notably, the results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine's odor profile from that of snapdragon flowers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

NASA Astrophysics Data System (ADS)

Xu, Philippe Q.; Bhartia, Pawan K.; Jaross, Glen R.; DeLand, Matthew T.; Larsen, Jack C.; Fleig, Albert; Kahn, Daniel; Zhu, Tong; Chen, Zhong; Gorkavyi, Nick; Warner, Jeremy; Linda, Michael; Chen, Hong G.; Kowitt, Mark; Haken, Michael; Hall, Peter

2014-10-01

The OMPS Limb Profiler (LP) was launched on board the NASA Suomi National Polar-orbiting Partnership (SNPP) satellite in October 2011. OMPS-LP is a limb-scattering hyperspectral sensor that provides ozone profiling capability at 1.8 km vertical resolution from cloud top to 60 km altitude. The use of three parallel slits allows global coverage in approximately four days. We have recently completed a full reprocessing of all LP data products, designated as Release 2, that improves the accuracy and quality of these products. Level 1 gridded radiance (L1G) changes include intra-orbit and seasonal correction of variations in wavelength registration, revised static and intra-orbit tangent height adjustments, and simplified pixel selection from multiple images. Ozone profile retrieval changes include removal of the explicit aerosol correction, exclusion of channels contaminated by stratospheric OH emission, a revised instrument noise characterization, improved synthetic solar spectrum, improved pressure and temperature ancillary data, and a revised ozone climatology. Release 2 data products also include aerosol extinction coefficient profiles derived with the prelaunch retrieval algorithm. Our evaluation of OMPS LP Release 2 data quality is good. Zonal average ozone profile comparisons with Aura MLS data typically show good agreement, within 5-10% over the altitude range 20-50 km between 60°S and 60°N. The aerosol profiles agree well with concurrent satellite measurements such as CALIPSO and OSIRIS, and clearly detect exceptional events such as volcanic eruptions and the Chelyabinsk bolide in February 2013.

Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

NASA Technical Reports Server (NTRS)

Xu, Q. Philippe; Bhartia, Pawan K.; Jaross, Glen R.; Deland, Matthew T.; Larsen, Jack C.; Fleig, Albert; Kahn, Daniel; Zhu, Tong; Chen, Zhong; Gorkavyi, Nick;

Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

PubMed

Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

1988-01-01

The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels.

Release profiles of phenytoin from new oral dosage form for the elderly.

PubMed

Watanabe, A; Hanawa, T; Sugihara, M; Yamamoto, K

1994-08-01

Utilization of the solid mass containing phenytoin, sodium caseinate and microcrystalline cellulose (MCC) as a new dosage form for the elderly was studied. The solid mass was prepared by treatment of the powder mixture with high pressure steam at 115 degrees C for 10 min. The stability of phenytoin in the solid mass was confirmed by infrared spectroscopy and high performance liquid chromatography. The extent of swelling of the solid mass containing phenytoin was investigated by water absorption test and gel strength test, and the swelling property was almost independent of the presence of phenytoin. The release profile of phenytoin from the solid mass was determined under various conditions, and was found to be influenced by the extent of swelling and the swollen state. It was observed that the protein adsorption to the phenytoin crystal surface and the addition of digestive enzyme also affected the release profile. In water, the solid mass prepared from a ground mixture of phenytoin and MCC showed remarkable improvement of release profile of phenytoin.

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

PubMed

Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

2018-02-01

The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

Heat and mass transfer during the cryopreservation of a bioartificial liver device: a computational model.

PubMed

Balasubramanian, Saravana K; Coger, Robin N

2005-01-01

Bioartificial liver devices (BALs) have proven to be an effective bridge to transplantation for cases of acute liver failure. Enabling the long-term storage of these devices using a method such as cryopreservation will ensure their easy off the shelf availability. To date, cryopreservation of liver cells has been attempted for both single cells and sandwich cultures. This study presents the potential of using computational modeling to help develop a cryopreservation protocol for storing the three dimensional BAL: Hepatassist. The focus is upon determining the thermal and concentration profiles as the BAL is cooled from 37 degrees C-100 degrees C, and is completed in two steps: a cryoprotectant loading step and a phase change step. The results indicate that, for the loading step, mass transfer controls the duration of the protocol, whereas for the phase change step, when mass transfer is assumed negligible, the latent heat released during freezing is the control factor. The cryoprotocol that is ultimately proposed considers time, cooling rate, and the temperature gradients that the cellular space is exposed to during cooling. To our knowledge, this study is the first reported effort toward designing an effective protocol for the cryopreservation of a three-dimensional BAL device.

The role of 5 HT6-receptor antagonists in Alzheimer's disease: an update.

PubMed

Khoury, Rita; Grysman, Noam; Gold, Jake; Patel, Kush; Grossberg, George T

2018-06-01

Despite recent advances in Alzheimer's disease (AD) research, no breakthrough treatments have been discovered. Cholinesterase inhibitors and the NMDA-receptor antagonist memantine are currently the two approved symptomatic treatments for AD. 5-HT6 receptor antagonism has recently emerged as a promising treatment strategy to improve cognition in AD, with a modest side-effect profile. Areas covered: 5-HT6 receptors, exclusively found in the central nervous system, modulate primarily GABA and glutamate levels, facilitating the secondary release of other neurotransmitters including dopamine, noradrenaline, and acetylcholine, all of which are compromised in AD. This review discusses findings of preclinical and phase I-III clinical trials conducted with three major 5-HT6 receptor antagonists: idalopirdine, intepirdine, and SUVN-502, in the field of AD. Expert opinion: Despite early positive findings, larger phase-III trials have failed to demonstrate any statistically significant impact on cognition for both idalopirdine and intepirdine, as adjunct to cholinesterase inhibitors. Paradoxically, 5-HT6 receptor agonists have also been shown to have cognitive enhancing properties. Thus, a better understanding of the mechanism of action of the 5-HT6 receptor and its ligands is warranted. Investigating 5-HT6 receptor partial or inverse agonists may be promising in future AD trials.

Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability.

PubMed

Ahmed, Tarek A; Ibrahim, Hany M; Samy, Ahmed M; Kaseem, Alaa; Nutan, Mohammad T H; Hussain, Muhammad Delwar

2014-06-01

The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueous medium, the PLGA in ISI and ISM systems solidified resulting in implants and microparticles, respectively. The in vitro drug release from the ISI system showed marked difference from miscible solvents (NMP and DMSO) than the partially miscible ones (triacetin and ethyl acetate), and the drug release decreased with increased PLGA concentration. In the ISM system, the initial in vitro drug release decreased with decreased ratio of polymer phase to external oil phase. In vivo studies in rats showed that ISM had slower drug release than the drug release from ISI. Also, the ISM system when compared to ISI system had significantly reduced initial burst effect. In vitro as well as the in vivo studies for both ISI and ISM systems showed sustained release of MK. The ISM system is suitable for sustained release of MK over 4-week period with a lower initial burst compared to the ISI system. Stability studies of the ISI and ISM formulations showed that MK is stable in the formulations stored at 4°C for more than 2 years.

Morphological Profiles of Playing Positions in Defense and Offense in Professional Men's Handball.

PubMed

Ante, Burger; Nikola, Foretić; Marijana Čavala

2015-07-01

The main scope of the study is concerned with the morphological profiles of playing positions in defense, offense and the combinations of these two phases of the game. Furthermore, study attempted to identify the difference between the morphological profiles of the individual playing positions. Entity sample of the study consist of the 148 players that participated in 45 matches of the World Men's Handball Championship which took place in Croatia in 2009. The study dealt with the differences between playing positions concerning basic morphological characteristics which are due to the selection based on roles and tasks that need to be carried out in each position. Moreover, morphological similarity of playing positions in offense and defense was noticed. It was determined that wing players play dominantly in the position of left back, external players in the position of right and center back whereas pivots participate in the positions of center, back and center forward positions in defense. Morphological profiles of playing positions in defense, offense and in the combination of these two phases of the game were determined. Identical positions on different sides in offense (left-right wing player, left-right back player) have shown that these positions are quite similar when it comes to morphological profile and playing position in defense. It can be concluded that some playing positions in offense are accompanied by the respective positions in defense. All positions are characterized by one or two morphological profiles.

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

PubMed Central

Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

2013-01-01

Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

Diffusion of volatile organics through porous snow: impact of surface adsorption and grain boundaries

NASA Astrophysics Data System (ADS)

Bartels-Rausch, T.; Wren, S. N.; Schreiber, S.; Riche, F.; Schneebeli, M.; Ammann, M.

2013-07-01

Release of trace gases from surface snow on earth drives atmospheric chemistry, especially in the polar regions. The gas-phase diffusion of methanol and of acetone through the interstitial air of snow was investigated in a well-controlled laboratory study in the temperature range of 223 to 263 K. The aim of this study was to evaluate how the structure of the snowpack, the interaction of the trace gases with the snow surface, and the grain boundaries influence the diffusion on timescales up to 1 h. The diffusive loss of these two volatile organics into packed snow samples was measured using a chemical ionization mass spectrometer. The structure of the snow was analysed by means of X-ray-computed micro-tomography. The observed diffusion profiles could be well described based on gas-phase diffusion and the known structure of the snow sample at temperatures ≥ 253 K. At colder temperatures, surface interactions start to dominate the diffusive transport. Parameterizing these interactions in terms of adsorption to the solid ice surface, i.e. using temperature-dependent air-ice partitioning coefficients, better described the observed diffusion profiles than the use of air-liquid partitioning coefficients. No changes in the diffusive fluxes were observed by increasing the number of grain boundaries in the snow sample by a factor of 7, indicating that for these volatile organic trace gases, uptake into grain boundaries does not play a role on the timescale of diffusion through porous surface snow. For this, a snow sample with an artificially high amount of ice grains was produced and the grain boundary surface measured using thin sections. In conclusion, we have shown that the diffusivity can be predicted when the structure of the snowpack and the partitioning of the trace gas to solid ice is known.

Diffusion of volatile organics through porous snow: impact of surface adsorption and grain boundaries

NASA Astrophysics Data System (ADS)

Bartels-Rausch, T.; Wren, S. N.; Schreiber, S.; Riche, F.; Schneebeli, M.; Ammann, M.

2013-03-01

Release of trace gases from surface snow on Earth drives atmospheric chemistry, especially in the polar regions. The gas-phase diffusion of methanol and of acetone through the interstitial air of snow was investigated in a well-controlled laboratory study in the temperature range of 223 to 263 K. The aim of this study was to evaluate how the structure of the snowpack, the interaction of the trace gases with the snow surface, and the grain boundaries influence the diffusion on timescales up to 1 h. The diffusive loss of these two volatile organics into packed snow samples was measured using a chemical ionization mass spectrometer. The structure of the snow was analyzed by means of X-ray computed micro-tomography. The observed diffusion profiles could be well described based on gas-phase diffusion and the known structure of the snow sample at temperatures ≥ 253 K. At colder temperatures surface interactions start to dominate the diffusive transport. Parameterizing these interactions in terms of adsorption to the solid ice surface, i.e. using temperature dependent air-ice partitioning coefficients, better described the observed diffusion profiles than the use of air-liquid partitioning coefficients. No changes in the diffusive fluxes were observed by increasing the number of grain boundaries in the snow sample by a factor of 7, indicating that for these volatile organic trace gases, uptake into grain boundaries does not play a role on the timescale of diffusion through porous surface snow. In conclusion, we have shown that the diffusivity can be predicted when the structure of the snowpack and the partitioning of the trace gas to solid ice is known.

Real-time investigation of cytochrome c release profiles in living neuronal cells undergoing amyloid beta oligomer-induced apoptosis

NASA Astrophysics Data System (ADS)

Lee, Jae Young; Park, Younggeun; Pun, San; Lee, Sung Sik; Lo, Joe F.; Lee, Luke P.

2015-06-01

Intracellular Cyt c release profiles in living human neuroblastoma undergoing amyloid β oligomer (AβO)-induced apoptosis, as a model Alzheimer's disease-associated pathogenic molecule, were analysed in a real-time manner using plasmon resonance energy transfer (PRET)-based spectroscopy.Intracellular Cyt c release profiles in living human neuroblastoma undergoing amyloid β oligomer (AβO)-induced apoptosis, as a model Alzheimer's disease-associated pathogenic molecule, were analysed in a real-time manner using plasmon resonance energy transfer (PRET)-based spectroscopy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02390d

Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

PubMed

Chang, Xiao; Liu, Shuai; Yu, Yong-Tao; Li, Yi-Xue; Li, Yuan-Yuan

2010-08-12

The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms.

Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder. A growth mixture modelling analysis.

PubMed

Sonuga-Barke, Edmund J S; Van Lier, Pol; Swanson, James M; Coghill, David; Wigal, Sharon; Vandenberghe, Mieke; Hatch, Simon

2008-06-01

To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting. GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference. The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.

Design and characterization of a biologically inspired quasi-passive prosthetic ankle-foot.

PubMed

Mooney, Luke M; Lai, Cara H; Rouse, Elliott J

2014-01-01

By design, commonly worn energy storage and release (ESR) prosthetic feet cannot provide biologically realistic ankle joint torque and angle profiles during walking. Additionally, their anthropomorphic, cantilever architecture causes their mechanical stiffness to decrease throughout the stance phase of walking, opposing the known trend of the biological ankle. In this study, the design of a quasi-passive pneumatic ankle-foot prosthesis is detailed that is able to replicate the biological ankle's torque and angle profiles during walking. The prosthetic ankle is comprised of a pneumatic piston, bending spring and solenoid valve. The mechanical properties of the pneumatic ankle prosthesis are characterized using a materials testing machine and the properties are compared to those from a common, passive ESR prosthetic foot. The characterization spanned a range of ankle equilibrium pressures and testing locations beneath the foot, analogous to the location of center of pressure within the stance phase of walking. The pneumatic ankle prosthesis was shown to provide biologically appropriate trends and magnitudes of torque, angle and stiffness behavior, when compared to the passive ESR prosthetic foot. Future work will focus on the development of a control system for the quasi-passive device and clinical testing of the pneumatic ankle to demonstrate efficacy.

Biomechanical analysis of the sidearm throwing motion for distance of a flying disc: a comparison of skilled and unskilled ultimate players.

PubMed

Sasakawa, Kei; Sakurai, Shinji

2008-09-01

Joint angles of the throwing limb were examined from the acceleration phase up until release for the sidearm throwing motion when using a flying disc. 17 individuals (ten skilled, seven unskilled) threw a disc as far as possible ten times. Throwing motions were recorded using three-dimensional high-speed videography. The initial condition of disc release and joint angle kinematics of the upper limb during the throwing motion were obtained. Mean (+/- standard deviation) throwing distance and disc spin rate were significantly greater for skilled throwers (51.4 +/- 6.6 m, 12.9 +/- 1.3 rps) than for unskilled throwers (29.5 +/- 7.6 m, 9.4 +/- 1.3 rps), although there was no significant difference in initial velocity of the disc between the two groups (skilled: 21.7 +/- 1.7m/s; unskilled: 20.7 +/- 2.5m/s). A marked difference in motion of supination/pronation of the forearm before disc release was identified, with the forearm supinated in the final acceleration phase leading up to disc release for the unskilled participants, while the forearm was pronated in the same phase for the skilled participants. These differences in joint kinematics could be related to differences in disc spin rate, and thus led to the substantial differences in throwing distance.

Formulation and in vitro evaluation of theophylline matrix tablets prepared by direct compression: Effect of polymer blends

PubMed Central

El-Bagory, Ibrahim; Barakat, Nahla; Ibrahim, Mohamed A.; El-Enazi, Fouza

2011-01-01

The deformation mechanism of pharmaceutical powders, used in formulating directly compressed matrix tablets, affects the characteristics of the formed tablets. Three polymers of different deformation mechanisms were tested for their impact on theophylline directly compressed tablets namely Kollidon SR (KL SR, plastic deformation), Ethylcellulose (EC, elastic deformation) and Carnauba wax (CW, brittle deformation) at different compression forces. However, tablets based mainly on KL SR, the plastically deformed polymer (TN1) exhibited the highest hardness values compared to the other formulae which are based on either blends of KL SR with CW, the very brittle deformed polymer. The upper detected force for TN formulae and the lower punch force were found to dependent mainly on the powder deformation. This difference is attributed to the work done during the compression phase as well as the work lost during the decompression phase. Furthermore, the release profiles of TN from formulae TN2 and TN4 that are based on the composition (2KL SR:1EC) and (1KL SR:2EC), respectively, were consistent with different deformation mechanisms of KL SR and EC and on the physicochemical properties like the water absorptive capacity of EC. Upon increasing the weight ratio of KL SR (TN2), the release rate was greatly retarded (39.4%, 37.1%, 35.0% and 33.6% released after 8 h at 5, 10, 15 and 20 kN. PMID:24115902

Dissociation between systemic and pulmonary anti‐inflammatory effects of dexamethasone in humans

PubMed Central

Bartko, Johann; Stiebellehner, Leopold; Derhaschnig, Ulla; Schoergenhofer, Christian; Schwameis, Michael; Prosch, Helmut

2016-01-01

Aims The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. Methods In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Results Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. Conclusions The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other. PMID:26647918

Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

PubMed Central

Mishra, Brahmeshwar; Mishra, Madhusmita; Yadav, Sarita Kumari

2017-01-01

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr’s index, solid state interaction by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection. PMID:28496463

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

PubMed

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Thermal modeling with solid/liquid phase change of the thermal energy storage experiment

NASA Technical Reports Server (NTRS)

Skarda, J. Raymond Lee

1991-01-01

A thermal model which simulates combined conduction and phase change characteristics of thermal energy storage (TES) materials is presented. Both the model and results are presented for the purpose of benchmarking the conduction and phase change capabilities of recently developed and unvalidated microgravity TES computer programs. Specifically, operation of TES-1 is simulated. A two-dimensional SINDA85 model of the TES experiment in cylindrical coordinates was constructed. The phase change model accounts for latent heat stored in, or released from, a node undergoing melting and freezing.

Modification of Sodium Release Using Porous Corn Starch and Lipoproteic Matrix.

PubMed

Christina, Josephine; Lee, Youngsoo

2016-04-01

Excessive sodium consumption can result in hypertension, diabetes, heart diseases, stroke, and kidney diseases. Various chips and extruded snacks, where salt is mainly applied on the product surface, accounted for almost 56% of snacks retail sales in 2010. Hence, it is important to target sodium reduction for those snack products. Past studies had shown that modifying the rate-release mechanism of sodium is a promising strategy for sodium reduction in the food industry. Encapsulation of salt can be a possible technique to control sodium release rate. Porous corn starch (PCS), created by enzymatic treatment and spray drying and lipoproteic matrix, created by gelation and freeze drying, were evaluated as carriers for controlled sodium release targeting topically applied salts. Both carriers encapsulated salt and their in vitro sodium release profiles were measured using a conductivity meter. The sodium release profiles of PCS treated with different enzymatic reaction times were not significantly different. Protein content and fat content altered sodium release profile from the lipoproteic matrix. The SEM images of PCS showed that most of the salt crystals coated the starch instead of being encapsulated in the pores while the SEM images and computed tomography scan of lipoproteic matrix showed salt dispersed throughout the matrix. Hence, PCS was found to have limitations as a sodium carrier as it could not effectively encapsulate salt inside its pores. The lipoproteic matrix was found to have a potential as a sodium carrier as it could effectively encapsulate salt and modify the sodium release profile. © 2016 Institute of Food Technologists®

Device and method for creating Gaussian aberration-corrected electron beams

DOEpatents

McMorran, Benjamin; Linck, Martin

2016-01-19

Electron beam phase gratings have phase profiles that produce a diffracted beam having a Gaussian or other selected intensity profile. Phase profiles can also be selected to correct or compensate electron lens aberrations. Typically, a low diffraction order produces a suitable phase profile, and other orders are discarded.

Detailed mechanism of benzene oxidation

NASA Technical Reports Server (NTRS)

Bittker, David A.

1987-01-01

A detailed quantitative mechanism for the oxidation of benzene in both argon and nitrogen diluted systems is presented. Computed ignition delay time for argon diluted mixtures are in satisfactory agreement with experimental results for a wide range of initial conditions. An experimental temperature versus time profile for a nitrogen diluted oxidation was accurately matched and several concentration profiles were matched qualitatively. Application of sensitivity analysis has given approximate rate constant expressions for the two dominant heat release reactions, the oxidation of C6H5 and C5H5 radicals by molecular oxygen.

Acid volatile sulfides oxidation and metals (Mn, Zn) release upon sediment resuspension: laboratory experiment and model development.

PubMed

Hong, Yong Seok; Kinney, Kerry A; Reible, Danny D

2011-03-01

Sediment from the Anacostia River (Washington, DC, USA) was suspended in aerobic artificial river water for 14 d to investigate the dynamics of dissolved metals release and related parameters including pH, acid volatile sulfides (AVS), and dissolved/solid phase Fe(2+). To better understand and predict the underlying processes, a mathematical model is developed considering oxidation of reduced species, dissolution of minerals, pH changes, and pH-dependent metals' sorption to sediment. Oxidation rate constants of elemental sulfur and zinc sulfide, and a dissolution rate constant of carbonate minerals, were adjusted to fit observations. The proposed model and parameters were then applied, without further calibration, to literature-reported experimental observations of resuspension in an acid sulfate soil collected in a coastal flood plain. The model provided a good description of the dynamics of AVS, Fe(2+), S(0)((s)), pH, dissolved carbonates concentrations, and the release of Ca((aq)), Mg((aq)), and Zn((aq)) in both sediments. Accurate predictions of Mn((aq)) release required adjustment of sorption partitioning coefficient, presumably due to the presence of Mn scavenging by phases not accounted for in the model. The oxidation of AVS (and the resulting release of sulfide-bound metals) was consistent with a two-step process, a relatively rapid AVS oxidation to elemental sulfur (S(0)((s))) and a slow oxidation of S(0)((s)) to SO(4)(2-)((aq)), with an associated decrease in pH from neutral to acidic conditions. This acidification was the dominant factor for the release of metals into the aqueous phase. Copyright © 2010 SETAC.

Energy distributions of H{sup +} fragments ejected by fast proton and electron projectiles in collision with H{sub 2}O molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barros, A. L. F. de; Lecointre, J.; Luna, H.

Experimental measurements of the kinetic energy distribution spectra of H{sup +} fragment ions released during radiolysis of water molecules in collision with 20, 50, and 100 keV proton projectiles and 35, 200, 400, and 1000 eV electron projectiles are reported using a pulsed beam and drift tube time-of-flight based velocity measuring technique. The spectra show that H{sup +} fragments carrying a substantial amount of energy are released, some having energies well in excess of 20 eV. The majority of the ions lie within the 0-5 eV energy range with the proton spectra showing an almost constant profile between 1.5 andmore » 5 eV and, below this, increasing gradually with decreasing ejection energy up to the near zero energy value while the electron spectra, in contrast, show a broad maximum between 1 and 3 eV and a pronounced dip around 0.25 eV. Beyond 5 eV, both projectile spectra show a decreasing profile with the electron spectra decreasing far more rapidly than the proton spectra. Our measured spectra thus indicate that major differences are present in the collision dynamics between the proton and the electron projectiles interacting with gas phase water molecules.« less

Sleep in prenatally restraint stressed rats, a model of mixed anxiety-depressive disorder.

PubMed

Mairesse, Jérôme; Van Camp, Gilles; Gatta, Eleonora; Marrocco, Jordan; Reynaert, Marie-Line; Consolazione, Michol; Morley-Fletcher, Sara; Nicoletti, Ferdinando; Maccari, Stefania

2015-01-01

Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression.

A Phase 2 Study of Chronocort, a Modified-Release Formulation of Hydrocortisone, in the Treatment of Adults With Classic Congenital Adrenal Hyperplasia

PubMed Central

Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J.; Daley, Lori-Ann; Digweed, Dena; Eckland, David J. A.; Van Ryzin, Carol; Nieman, Lynnette K.; Arlt, Wiebke; Merke, Deborah P.

2015-01-01

Context: Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. Objectives: The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Design, Setting, and Patients: Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. Main Outcome Measures: The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). Results: In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700–1500 h; P = .002), and afternoon (1500–2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700–1500 h; P = .02) 17-OHP AUC. Conclusions: Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH. PMID:25494662

A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia.

PubMed

Mallappa, Ashwini; Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J; Daley, Lori-Ann; Digweed, Dena; Eckland, David J A; Van Ryzin, Carol; Nieman, Lynnette K; Arlt, Wiebke; Ross, Richard J; Merke, Deborah P

2015-03-01

Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700-1500 h; P = .002), and afternoon (1500-2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700-1500 h; P = .02) 17-OHP AUC. Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.

Effects of a Physical Exercise Program (PEP-Aut) on Autistic Children’s Stereotyped Behavior, Metabolic and Physical Activity Profiles, Physical Fitness, and Health-Related Quality of Life: A Study Protocol

PubMed Central

Ferreira, José Pedro; Andrade Toscano, Chrystiane Vasconcelos; Rodrigues, Aristides Machado; Furtado, Guilherme Eustaquio; Barros, Mauro Gomes; Wanderley, Rildo Souza; Carvalho, Humberto Moreira

2018-01-01

Physical exercise has shown positive effects on symptomatology and on the reduction of comorbidities in population with autism spectrum disorder (ASD). However, there is still no consensus about the most appropriate exercise intervention model for children with ASD. The physical exercise program for children with autism (PEP-Aut) protocol designed allow us to (i) examine the multivariate associations between ASD symptoms, metabolic profile, physical activity level, physical fitness, and health-related quality of life of children with ASD; (ii) assess the effects of a 40-week exercise program on all these aspects of children with ASD. The impact of the exercise program will be assessed based on the sequence of the two phases. Phase 1 is a 12-week cross-sectional study assessing the symptomatology, metabolic profile, physical fitness and physical activity levels, socioeconomic status profile, and health-related quality of life of participants. This phase is the baseline of the following phase. Phase 2 is a 48-week intervention study with a 40-week intervention with exercise that will take place in a specialized center for children with ASD in the city of Maceió-Alagoas, Brazil. The primary outcomes will be change in the symptomatic profile and the level of physical activity of children. Secondary outcomes will be anthropometric and metabolic profiles, aerobic function, grip strength, socioeconomic status, and health-related quality of life. The study will provide critical information on the efficacy of exercise for children with ASD and help guide design and delivery of future programs. PMID:29552551

Preliminary evaluation of an aqueous wax emulsion for controlled-release coating.

PubMed

Walia, P S; Stout, P J; Turton, R

1998-02-01

The purpose of this work was to evaluate the use of an aqueous carnauba wax emulsion (Primafresh HS, Johnson Wax) in a spray-coating process. This involved assessing the effectiveness of the wax in sustaining the release of the drug, theophylline. Second, the process by which the drug was released from the wax-coated pellets was modeled. Finally, a method to determine the optimum blend of pellets with different wax thicknesses, in order to yield a zero-order release profile of the drug, was addressed. Nonpareil pellets were loaded with theophylline using a novel powder coating technique. These drug-loaded pellets were then coated with different levels of carnauba wax in a 6-in. diameter Plexiglas fluid bed with a 3.5-in. diameter Wurster partition. Drug release was measured using a spin-filter dissolution device. The study resulted in continuous carnauba wax coatings which showed sustained drug release profile characteristics typical of a barrier-type, diffusion-controlled system. The effect of varying wax thickness on the release profiles was investigated. It was observed that very high wax loadings would be required to achieve long sustained-release times. The diffusion model, developed to predict the release of the drug, showed good agreement with the experimental data. However, the data exhibited an initial lag-time for drug release which could not be predicted a priori based on the wax coating thickness. A method of mixing pellets with different wax thicknesses was proposed as a way to approximate zero-order release.

Effect of particle size, polydispersity and polymer degradation on progesterone release from PLGA microparticles: Experimental and mathematical modeling.

PubMed

Busatto, Carlos; Pesoa, Juan; Helbling, Ignacio; Luna, Julio; Estenoz, Diana

2018-01-30

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results. Copyright © 2017 Elsevier B.V. All rights reserved.

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Physical characterization and in vitro biological impact of highly aggregated antibodies separated into size-enriched populations by fluorescence-activated cell sorting

PubMed Central

Telikepalli, Srivalli; Shinogle, Heather E.; Thapa, Prem S.; Kim, Jae Hyun; Deshpande, Meghana; Jawa, Vibha; Middaugh, C. Russell; Narhi, Linda O.; Joubert, Marisa K.; Volkin, David B.

2015-01-01

An IgG2 monoclonal antibody (mAb) solution was subjected to stirring, generating high concentrations of nanometer and subvisible particles, which were then successfully size enriched into different size bins by low speed centrifugation or a combination of gravitational sedimentation and Fluorescence-Activated Cell Sorting (FACS). The size-fractionated mAb particles were assessed for their ability to elicit the release of cytokines from a population of donor-derived human peripheral blood mononuclear cells (PBMC) at two phases of the immune response. Fractions enriched in nanometer-sized particles showed a lower response than those enriched in micron-sized particles in this assay. Particles of 5–10 μm in size displayed elevated cytokine release profiles compared to other size ranges. Stir-stressed mAb particles had amorphous morphology, contained protein with partially altered secondary structure, elevated surface hydrophobicity (compared to controls), and trace levels of elemental fluorine. FACS size-enriched the mAb particle samples, yet did not notably alter the overall morphology or composition of particles as measured by Microflow imaging, Transmission Electron Microscopy, and Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy. The utility and limitations of FACS for size separation of mAb particles and potential of in-vitro PBMC studies to rank order the immunogenic potential of various types of mAb particles is discussed. PMID:25753756

Design of novel injectable in-situ forming scaffolds for non-surgical treatment of periapical lesions: In-vitro and in-vivo evaluation.

PubMed

Shamma, Rehab N; Elkasabgy, Nermeen A; Mahmoud, Azza A; Gawdat, Shaimaa I; Kataia, Mohamed M; Abdel Hamid, Mohamed A

2017-04-15

Periapical lesions are considered one of the common pathological conditions affecting alveolar bone. The primary focus of this study was to investigate the effectiveness of formulating an injectable in-situ forming scaffold-loaded with risedronate (bone resorption inhibitor) and with lornoxicam (anti-inflammatory drug) for the non-surgical treatment of periapical lesions. The scaffolds were prepared using solvent-induced phase inversion technique. Two insoluble copolymers were investigated namely; PLGA (ester-terminal) and PLGA-A (acid-terminal), additionally, SAIB was added as a high viscosity water-insoluble carrier. The addition of porogenic agents like hydrolyzed collagen was also investigated. The prepared scaffolds were characterized by analyzing their in-vitro release, DSC and rheological properties, besides their morphological properties. The results showed that the scaffolds prepared using 30% (w/v) PLGA or combined PLGA: SAIB (1:1, w/w) with total polymer concentration of 30% (w/v) possessed the most sustained drug release profile. Selected scaffolds were tested for their therapeutic effect to study the effect of porogenic agent, anti-inflammatory drug and risedronate in periapical lesions induced in dogs' teeth. Results declared that the selected scaffolds succeeded in improving the inflammation and enhancing the formation of new bony regions confirming the success of the prepared scaffolds as an innovative approach in the treatment of bone defects. Copyright © 2017 Elsevier B.V. All rights reserved.

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

Adenoviral vector tethering to metal surfaces via hydrolysable cross-linkers for the modulation of vector release and transduction

PubMed Central

Fishbein, Ilia; Forbes, Scott P.; Chorny, Michael; Connolly, Jeanne M.; Adamo, Richard F.; Corrales, Ricardo; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

The use of arterial stents and other medical implants as a delivery platform for surface immobilized gene vectors allows for safe and efficient localized expression of therapeutic transgenes. In this study we investigate the use of hydrolysable cross-linkers with distinct kinetics of hydrolysis for delivery of gene vectors from polyallylamine bisphosphonate-modified metal surfaces. Three cross-linkers with the estimated t1/2 of ester bonds hydrolysis of 5, 12 and 50 days demonstrated a cumulative 20%, 39% and 45% vector release, respectively, after 30 days exposure to physiological buffer at 37°C. Transgene expression in endothelial and smooth muscles cells transduced with substrate immobilized adenovirus resulted in significantly different expression profiles for each individual cross-linker. Furthermore, immobilization of adenoviral vectors effectively extended their transduction effectiveness beyond the initial phase of release. Transgene expression driven by adenovirus-tethered stents in rat carotid arteries demonstrated that a faster rate of cross-linker hydrolysis resulted in higher expression levels at day 1, which declined by day 8 after stent implantation, while inversely, slower hydrolysis was associated with increased arterial expression at day 8 in comparison with day 1. In conclusion, adjustable release of transduction-competent adenoviral vectors from metallic surfaces can be achieved, both in vitro and in vivo, through surface immobilization of adenoviral vectors using hydrolysable cross-linkers with structure-specific release kinetics. PMID:23777912

Phase-field model for the two-phase lithiation of silicon

NASA Astrophysics Data System (ADS)

Gao, Fangliang; Hong, Wei

2016-09-01

As an ideal anode material, silicon has the highest lithium-ion capacity in theory, but the broader application is limited by the huge volumetric strain caused by lithium insertion and extraction. To better understand the physical process and to resolve the related reliability issue, enormous efforts have been made. Recent experiments observed sharp reaction fronts in both crystalline and amorphous silicon during the first lithiation half-cycle. Such a concentration profile indicates that the process is likely to be reaction limited. Based on this postulation, a phase-field model is developed and implemented into a finite-element code to simulate the coupled large inelastic deformation and motion of the reaction front in a silicon electrode. In contrast to most existing models, the model treats both volumetric and deviatoric inelastic deformation in silicon as a direct consequence of the lithiation at the reaction front. The amount of deviatoric deformation is determined by using the recently developed kinetic model of stress-induced anisotropic reaction. By considering the role of stress in the lithiation process, this model successfully recovers the self-limiting phenomenon of silicon electrodes, and relates it to the local geometry of electrodes. The model is also used to evaluate the energy-release rate of the surface crack on a spherical electrode, and the result suggests a critical size of silicon nanoparticles to avert fracture. As examples, the morphology evolution of a silicon disk and a Si nanowire during lithiation are also investigated.

Time Course Exo-Metabolomic Profiling in the Green Marine Macroalga Ulva (Chlorophyta) for Identification of Growth Phase-Dependent Biomarkers

PubMed Central

Alsufyani, Taghreed; Weiss, Anne; Wichard, Thomas

2017-01-01

The marine green macroalga Ulva (Chlorophyta) lives in a mutualistic symbiosis with bacteria that influence growth, development, and morphogenesis. We surveyed changes in Ulva’s chemosphere, which was defined as a space where organisms interact with each other via compounds, such as infochemicals, nutrients, morphogens, and defense compounds. Thereby, Ulva mutabilis cooperates with bacteria, in particular, Roseovarius sp. strain MS2 and Maribacter sp. strain MS6 (formerly identified as Roseobacter sp. strain MS2 and Cytophaga sp. strain MS6). Without this accompanying microbial flora, U. mutabilis forms only callus-like colonies. However, upon addition of the two bacteria species, in effect forming a tripartite community, morphogenesis can be completely restored. Under this strictly standardized condition, bioactive and eco-physiologically-relevant marine natural products can be discovered. Solid phase extracted waterborne metabolites were analyzed using a metabolomics platform, facilitating gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analysis, combined with the necessary acquisition of biological metadata. Multivariate statistics of the GC-MS and LC-MS data revealed strong differences between Ulva’s growth phases, as well as between the axenic Ulva cultures and the tripartite community. Waterborne biomarkers, including glycerol, were identified as potential indicators for algal carbon source and bacterial-algal interactions. Furthermore, it was demonstrated that U. mutabilis releases glycerol that can be utilized for growth by Roseovarius sp. MS2. PMID:28075408

Heating and Cooling of Coronal Loops with Turbulent Suppression of Parallel Heat Conduction.

PubMed

Bian, Nicolas; Emslie, A Gordon; Horne, Duncan; Kontar, Eduard P

2018-01-10

Using the "enthalpy-based thermal evolution of loops" (EBTEL) model, we investigate the hydrodynamics of the plasma in a flaring coronal loop in which heat conduction is limited by turbulent scattering of the electrons that transport the thermal heat flux. The EBTEL equations are solved analytically in each of the two (conduction-dominated and radiation-dominated) cooling phases. Comparison of the results with typical observed cooling times in solar flares shows that the turbulent mean free path λ T lies in a range corresponding to a regime in which classical (collision-dominated) conduction plays at most a limited role. We also consider the magnitude and duration of the heat input that is necessary to account for the enhanced values of temperature and density at the beginning of the cooling phase and for the observed cooling times. We find through numerical modeling that in order to produce a peak temperature ≃1.5 × 10 7 K and a 200 s cooling time consistent with observations, the flare-heating profile must extend over a significant period of time; in particular, its lingering role must be taken into consideration in any description of the cooling phase. Comparison with observationally inferred values of post-flare loop temperatures, densities, and cooling times thus leads to useful constraints on both the magnitude and duration of the magnetic energy release in the loop, as well as on the value of the turbulent mean free path λ T .

Hyper thin 3D edge measurement of honeycomb core structures based on the triangular camera-projector layout & phase-based stereo matching.

PubMed

Jiang, Hongzhi; Zhao, Huijie; Li, Xudong; Quan, Chenggen

2016-03-07

We propose a novel hyper thin 3D edge measurement technique to measure the profile of 3D outer envelope of honeycomb core structures. The width of the edges of the honeycomb core is less than 0.1 mm. We introduce a triangular layout design consisting of two cameras and one projector to measure hyper thin 3D edges and eliminate data interference from the walls. A phase-shifting algorithm and the multi-frequency heterodyne phase-unwrapping principle are applied for phase retrievals on edges. A new stereo matching method based on phase mapping and epipolar constraint is presented to solve correspondence searching on the edges and remove false matches resulting in 3D outliers. Experimental results demonstrate the effectiveness of the proposed method for measuring the 3D profile of honeycomb core structures.

Binary blend of glyceryl monooleate and glyceryl monostearate for magnetically induced thermo-responsive local drug delivery system.

PubMed

Mengesha, Abebe E; Wydra, Robert J; Hilt, J Zach; Bummer, Paul M

2013-12-01

To develop a novel monoglycerides-based thermal-sensitive drug delivery system, specifically for local intracavitary chemotherapy. Lipid matrices containing mixtures of glyceryl monooleate (GMO) and glyceryl monostearate (GMS) were evaluated for their potential application as magnetically induced thermo-responsive local drug delivery systems using a poorly water-soluble model drug, nifedipine (NF). Oleic acid-modified iron oxide (OA-Fe3O4) nanoparticles were embedded into the GMO-GMS matrix for remote activation of the drug release using an alternating magnetic field (AMF). The crystallization behavior of binary blends of GMO and GMS as characterized by DSC did show temperature dependent phase transition. GMO-GMS (75:25 wt%) blend showed a melting (T m ) and crystallization (T c ) points at 42°C and 37°C, respectively indicating the potential of the matrix to act as an 'on-demand' drug release. The matrix released only 35% of the loaded drug slowly in 10 days at 37°C whereas 96% release was obtained at 42°C. A concentration of 0.5% OA-Fe3O4 heated the matrix to 42.3 and 45.5°C within 5 min and 10 min of AMF exposure, respectively. The in vitro NF release profiles form the monoglycerides matrix containing 0.5% OA-Fe3O4 nanoparticles after AMF activation confirmed the thermo-responsive nature of the matrix that could provide pulsatile drug release 'on-demand'.

Residual waste from Hanford tanks 241-C-203 and 241-C-204. 2. Contaminant release model.

PubMed

Cantrell, Kirk J; Krupka, Kenneth M; Deutsch, William J; Lindberg, Michael J

2006-06-15

Release of U and 99Tc from residual sludge in Hanford waste tanks 241-C-203 and 241-C-204 atthe U.S. Department of Energy's (DOE) Hanford Site in southeastern Washington state was quantified by water-leaching, selective extractions, empirical solubility measurements, and thermodynamic modeling. A contaminant release model was developed based on these experimental results and solid-phase characterization results presented elsewhere. Uranium release was determined to be controlled by two phases and occurred in three stages. In the first stage, U release is controlled by the solubility of tejkaite, which is suppressed by high concentrations of sodium released from the dissolution of NaNO3 in the residual sludges. Equilibrium solubility calculations indicate the U released during this stage will have a maximum concentration of 0.021 M. When all the NaNO3 has dissolved from the sludge, the solubility of the remaining cejkaite will increase to 0.28 M. After cejkaite has completely dissolved, the majority of the remaining U is in the form of poorly crystalline Na2U2O7 [or clarkeite Na[(UO2)O(OH)](H20)0-1]. In contact with Hanford groundwater this phase is not stable, and becquerelite becomes the U solubility controlling phase, with a calculated equilibrium concentration of 1.2 x 10(-4) M. For Tc, a significant fraction of its concentration in the residual sludge was determined to be relatively insoluble (20 wt % for C-203 and 80 wt % for C-204). Because of the low concentrations of Tc in these sludge materials, the characterization studies did not identify any discrete Tc solids phases. Release of the soluble fraction of Tc was found to occur concomitantly with NO3-. It was postulated that a NaNO3-NaTcO4 solid solution could be responsible for this behavior. The Tc release concentrations for the soluble fraction were estimated to be 2.4 x 10-6 M for C-203 and 2.7 x 10(-5) M for C-204. Selective extraction results indicated that the recalcitrant fraction of Tc was associated with Fe oxides. Release of the recalcitrant fraction of Tc was assumed to be controlled by dissolution of Fe oxide in the form of ferrihydrite. Based on this assumption and measured values for the ratio of recalcitrant Tc to total Fe in each bulk sludge, the release concentration of the recalcitrant fraction of Tc was calculated to be 3.9 x 10(-12) M for C-203 and 10.0 x 10(-12) M for C-204.

Synthesis and toxicity evaluation of hydrophobic ionic liquids for volatile organic compounds biodegradation in a two-phase partitioning bioreactor.

PubMed

Rodriguez Castillo, Alfredo Santiago; Guihéneuf, Solène; Le Guével, Rémy; Biard, Pierre-François; Paquin, Ludovic; Amrane, Abdeltif; Couvert, Annabelle

2016-04-15

Synthesis of several hydrophobic ionic liquids (ILs), which might be selected as good candidates for degradation of hydrophobic volatile organic compounds in a two-phase partitioning bioreactor (TPPB), were carried out. Several bioassays were also realized, such as toxicity evaluation on activated sludge and zebrafish, cytotoxicity, fluoride release in aqueous phase and biodegradability in order to verify their possible effects in case of discharge in the aquatic environment and/or human contact during industrial manipulation. The synthesized compounds consist of alkylimidazoliums, functionalized imidazoliums, isoqinoliniums, triazoliums, sulfoniums, pyrrolidiniums and morpholiniums and various counter-ions such as: PF6(-), NTf2(-) and NfO(-). Toxicity evaluation on activated sludge of each compound (5% v/v of IL) was assessed by using a glucose uptake inhibition test. Toxicity against zebrafish and cytotoxicity were evaluated by the ImPACCell platform of Rennes (France). Fluoride release in water was estimated by regular measurements using ion chromatography equipment. IL biodegradability was determined by measuring BOD28 of aqueous samples (compound concentration,1mM). All ILs tested were not biodegradable; while some of them were toxic toward activated sludge. Isoquinolinium ILs were toxic to human cancerous cell lines. Nevertheless no toxicity was found against zebrafish Danio rerio. Only one IL released fluoride after long-time agitation. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

clusterProfiler: an R package for comparing biological themes among gene clusters.

PubMed

Yu, Guangchuang; Wang, Li-Gen; Han, Yanyan; He, Qing-Yu

2012-05-01

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.

Tracking the Remodeling of SNOMED CT's Bacterial Infectious Diseases.

PubMed

Ochs, Christopher; Case, James T; Perl, Yehoshua

2016-01-01

SNOMED CT's content undergoes many changes from one release to the next. Over the last year SNOMED CT's Bacterial infectious disease subhierarchy has undergone significant editing to bring consistent modeling to its concepts. In this paper we analyze the stated and inferred structural modifications that affected the Bacterial infectious disease subhierarchy between the Jan 2015 and Jan 2016 SNOMED CT releases using a two-phased approach. First, we introduce a methodology for creating a human readable list of changes. Next, we utilize partial-area taxonomies, which are compact summaries of SNOMED CT's content and structure, to identify the "big picture" changes that occurred in the subhierarchy. We illustrate how partial-area taxonomies can be used to help identify groups of concepts that were affected by these editing operations and the nature of these changes. Modeling issues identified using our two-phase methodology are discussed.

In vitro controlled release of clove essential oil in self-assembly of amphiphilic polyethylene glycol-block-polycaprolactone.

PubMed

Thonggoom, O; Punrattanasin, N; Srisawang, N; Promawan, N; Thonggoom, R

2016-05-01

In this study, a micellar delivery system with an amphiphilic diblock copolymer of poly (ethylene glycol) and poly (ɛ-caprolactone) was synthesised and used to incorporate hydrophobic clove essential oil (CEO). To determine an optimal delivery system, the effects of the copolymer's hydrophobic block length and the CEO-loading content on the encapsulation of CEO were investigated. Percentages of entrapment efficiency (%EE), CEO loading (%CEO), and in vitro release profiles were determined. The size, size distribution, zeta potential, and morphology of the obtained micelles were determined by DLS, FE-SEM, and TEM. The %EE, %CEO, and in vitro release profiles of CEO incorporated in micelles were analysed by HPLC. The study revealed a sustained release profile of CEO from CEO-loaded micelles. The results indicate the successful formulation of CEO-loaded PEG-b-PCL micelle nanoparticles. It is suggested that this micelle system has considerably potential applications in the sustained release of CEO in intravascular drug delivery.

Designing in vivo concentration gradients with discrete controlled release: a computational model

NASA Astrophysics Data System (ADS)

Walker, Edgar Y.; Barbour, Dennis L.

2010-08-01

One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.

On-line monitoring of in-vitro oral bioaccessibility tests as front-end to liquid chromatography for determination of chlorogenic acid isomers in dietary supplements.

PubMed

Kremr, Daniel; Cocovi-Solberg, David J; Bajerová, Petra; Ventura, Karel; Miró, Manuel

2017-05-01

A novel fully automated in-vitro oral dissolution test assay as a front-end to liquid chromatography has been developed and validated for on-line chemical profiling and monitoring of temporal release profiles of three caffeoylquinic acid (CQA) isomers, namely, 3-CQA,4-CQA and 5-CQA, known as chlorogenic acids, in dietary supplements. Tangential-flow filtration is harnessed as a sample processing approach for on-line handling of CQA containing extracts of hard gelatin capsules and introduction of protein-free samples into the liquid chromatograph. Oral bioaccessibility/dissolution test assays were performed at 37.0±0.5°C as per US Pharmacopeia recommendations using pepsin with activity of ca. 749,000 USP units/L in 0.1mol/L HCl as the extraction medium and a paddle apparatus stirred at 50rpm. CQA release rates and steady-state dissolution conditions were determined accurately by fitting the chromatographic datasets, namely, the average cumulative concentrations of bioaccessible pools of every individual isomer monitored during 200min, with temporal resolutions of ≥10min, to a first-order dissolution kinetic model. Distinct solid-to-liquid phase ratios in the mimicry of physiological extraction conditions were assessed. Relative standard deviations for intra-day repeatability and inter-day intermediate precision of 5-CQA within the 5-40µg/mL concentration range were <3.4% and <5.5%, respectively. Trueness of the automatic flow method for determination of 5-CQA released from dietary supplements in gastric fluid surrogate was demonstrated by spike recoveries, spanning from 91.5-104.0%, upon completion of the dissolution process. The proposed hyphenated setup was resorted for evaluating potential differences in dissolution profiles and content of the three most abundant chlorogenic acid isomers in dietary supplements from varied manufacturers. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

PubMed Central

Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

2015-01-01

The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge.

PubMed

Pillai, Anil Kumar; Silvers, William; Christensen, Preston; Riegel, Matthew; Adams-Huet, Beverley; Lingvay, Ildiko; Sun, Xiankai; Öz, Orhan K

2015-01-01

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas.

Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge

PubMed Central

Pillai, Anil Kumar; Silvers, William; Christensen, Preston; Riegel, Matthew; Adams-Huet, Beverley; Lingvay, Ildiko; Sun, Xiankai; Öz, Orhan K.

2015-01-01

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas. PMID:26273676

Controlled release of tetracycline-HCl from halloysite-polymer composite films.

PubMed

Ward, Christopher J; Song, Shang; Davis, Edward W

2010-10-01

The first direct comparison between two common methods for loading halloysite with a small molecule for controlled release is presented. While the methods differ in the degree of simplicity, they provide essentially the same level of loading and release kinetics. A tentative explanation of the "burst" effect often seen in the release of low molecular weight molecules from halloysite is provided. The ability of halloysite to mediate the release rate of a water soluble drug, tetracycline, from solution cast polyvinyl alcohol and polymethyl methacrylate films was evaluated. In some films, montmorillonite was also incorporated. The addition of montmorillonite to solutions used to cast tetracycline containing films significantly reduced the release rate from the dried films. The same overall effect was seen when the drug was loaded into halloysite prior to preparation of the films. In both cases, the release was best fit with the simple Higuchi model. However, when montmorillonite was added to solutions of polyvinyl alcohol and drug loaded halloysite the release profiles were better fit by the Ritgar-Peppas model for anomalous transport. Release from polymethyl methacrylate was reduced by a factor of three by incorporating the drug in halloysite prior to producing the films.

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method.

PubMed

Lee, J; Park, T G; Choi, H

2000-02-25

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones

PubMed Central

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-01-01

Key points Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin–phospholipid interaction. Abstract Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. PMID:25981717

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

PubMed

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-07-01

Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Simultaneous measurement of passage through the restriction point and MCM loading in single cells

PubMed Central

Håland, T. W.; Boye, E.; Stokke, T.; Grallert, B.; Syljuåsen, R. G.

2015-01-01

Passage through the Retinoblastoma protein (RB1)-dependent restriction point and the loading of minichromosome maintenance proteins (MCMs) are two crucial events in G1-phase that help maintain genome integrity. Deregulation of these processes can cause uncontrolled proliferation and cancer development. Both events have been extensively characterized individually, but their relative timing and inter-dependence remain less clear. Here, we describe a novel method to simultaneously measure MCM loading and passage through the restriction point. We exploit that the RB1 protein is anchored in G1-phase but is released when hyper-phosphorylated at the restriction point. After extracting cells with salt and detergent before fixation we can simultaneously measure, by flow cytometry, the loading of MCMs onto chromatin and RB1 binding to determine the order of the two events in individual cells. We have used this method to examine the relative timing of the two events in human cells. Whereas in BJ fibroblasts released from G0-phase MCM loading started mainly after the restriction point, in a significant fraction of exponentially growing BJ and U2OS osteosarcoma cells MCMs were loaded in G1-phase with RB1 anchored, demonstrating that MCM loading can also start before the restriction point. These results were supported by measurements in synchronized U2OS cells. PMID:26250117

Dynamic High-Pressure Behavior of Hierarchical Heterogeneous Geological Materials

DTIC Science & Technology

2016-04-01

sandwiched between two 25µm FEP copolymer layers attached to the copper driver plate . The total package thickness with thin-film epoxy on all bonding...public release. 3 OUTLINE Page # ABSTRACT 2 1. BACKGROUND 4 2. CHARACTERISTICS OF SAND INVESTIGATED 8 3. PLATE ...constituents, phases, inter-phase boundaries ; distributions in shock states; as well as the structural evolutions which can result in strain

The application of the high-speed photography in the experiments of boiling liquid expanding vapor explosions

NASA Astrophysics Data System (ADS)

Chen, Sining; Sun, Jinhua; Chen, Dongliang

2007-01-01

The liquefied-petroleum gas tank in some failure situations may release its contents, and then a series of hazards with different degrees of severity may occur. The most dangerous accident is the boiling liquid expanding vapor explosion (BLEVE). In this paper, a small-scale experiment was established to experimentally investigate the possible processes that could lead to a BLEVE. As there is some danger in using LPG in the experiments, water was used as the test fluid. The change of pressure and temperature was measured during the experiment. The ejection of the vapor and the sequent two-phase flow were recorded by a high-speed video camera. It was observed that two pressure peaks result after the pressure is released. The vapor was first ejected at a high speed; there was a sudden pressure drop which made the liquid superheated. The superheated liquid then boiled violently causing the liquid contents to swell, and also, the vapor pressure in the tank increased rapidly. The second pressure peak was possibly due to the swell of this two-phase flow which was likely to violently impact the wall of the tank with high speed. The whole evolution of the two-phase flow was recorded through photos captured by the high-speed video camera, and the "two step" BLEVE process was confirmed.

In situ release rates of Cu and Zn from commercial antifouling paints at different salinities.

PubMed

Lagerström, Maria; Lindgren, J Fredrik; Holmqvist, Albin; Dahlström, Mia; Ytreberg, Erik

2018-02-01

Antifouling paints are environmentally risk assessed based on their biocidal release rates to the water phase. In situ release rates of copper (Cu) and zinc (Zn) were derived for five commercial paints in two recreational marinas with different salinities (5 and 14 PSU) using an X-Ray Fluorescence spectrometer (XRF). Salinity was found to significantly affect the Cu release, with twice the amount of Cu released at the higher salinity, while its influence on the Zn release was paint-specific. Site-specific release rates for water bodies with salinity gradients, e.g. the Baltic Sea, are therefore necessary for more realistic risk assessments of antifouling paints. Furthermore, the in situ release rates were up to 8 times higher than those generated using standardized laboratory or calculation methods. The environmental risk assessment repeated with the field release rates concludes that it is questionable whether the studied products should be allowed on the Swedish market. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Swiftly moving focus points and forming shapes through the scattering media

NASA Astrophysics Data System (ADS)

Tran, Vinh; Sahoo, Sujit Kumar; Tang, Dongliang; Dang, Cuong

2018-02-01

Propagation of light through scattering media such as ground glass or biological tissue limits the quality and intensity of focusing point. Wave front shaping technique which uses spatial light modulator (SLM) devices to reshape the field profile of incoming light, is considered as one of the most effective and convenient methods. Advanced biomedical or manufacturing applications require drawing various contours or shapes quickly and precisely. However, creating each shape behind the scattering medium needs different phase profiles, which are time consuming to optimize or measure. Here, we demonstrate a technique to draw various shapes or contours behind the scattering medium by swiftly moving the focus point without any mechanical movements. Our technique relies on the existence of speckle correlation property in scattering media, also known as optical memory effect. In our procedure, we first modulate the phase-only SLM to create the focus point on the other side of scattering medium. Then, we digitally shift the preoptimized phase profile on the SLM and ramp it to tilt the beam accordingly. Now, the incoming beam with identical phase profile shines on the same scattering region at a tilted angle to regenerate the focus point at the desired position due to memory effect. Moreover, with linear combination of different field patterns, we can generate a single phase profile on SLM to produce two, three or more focus points simultaneously on the other side of a turbid medium. Our method could provide a useful tool for prominent applications such as opto-genetic excitation, minimally invasive laser surgery and other related fields.

Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate.

PubMed

Gonzalez Novoa, Gelsys Ananay; Heinämäki, Jyrki; Mirza, Sabir; Antikainen, Osmo; Colarte, Antonio Iraizoz; Paz, Alberto Suzarte; Yliruusi, Jouko

2005-02-01

Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer-polymer and drug-polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug-polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug-polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.

Experimental and modeling studies showing the effect of lipid type and level on flavor release from milk-based liquid emulsions.

PubMed

Roberts, Deborah D; Pollien, Philippe; Watzke, Brigitte

2003-01-01

The purpose of this work was to study two key parameters of the lipid phase that influence flavor release-lipid level and lipid type-and to relate the results to a mass balance partition coefficient-based mathematical model. Release of 10 volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was monitored by 1-min headspace sampling with a solid-phase microextraction fiber, followed by GC-MS analysis. As compared to the observations for milk fat, changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a monoglyceride-based surfactant did not influence the volatiles release. However, increasing the solid fat content was found to increase the release. At 25 degrees C, and even more so at 10 degrees C, concurrent with an increase in their solid fat content, hydrogenated palm fat emulsions showed increased flavor release over that observed for emulsions made with coconut oil, coconut oil with surfactant, milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions had zero solid fat content, there was no difference in flavor release from that observed for milk fat emulsions. Varying milk fat at nine levels between 0 and 4.5% showed a systematic dependence of the release on the lipid level, dependent on compound lipophilicity. Close correlations were found between the experimental and model predictions with lipid level and percent liquid lipid as variables.

Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell

PubMed Central

1985-01-01

A microprocessor-controlled system of microinjections and microaspirations has been developed to change, within approximately 1 ms, the [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils (0.3-0.4 micron radius) of a skinned canine cardiac Purkinje cell (2.5-4.5 micron overall radius) at different phases of a Ca2+ transient. Simultaneously monitoring tension and aequorin bioluminescence provided two methods for estimating the peak myoplasmic [free Ca2+] reached during the spontaneous cyclic Ca2+ release from the SR obtained in the continuous presence of a bulk solution [free Ca2+] sufficiently high to overload the SR. These methods gave results in excellent agreement for the spontaneous Ca2+ release under a variety of conditions of pH and [free Mg2+], and of enhancement of Ca2+ release by calmodulin. Disagreement was observed, however, when the Ca2+ transient was modified during its ascending phase. The experiments also permitted quantification of the aequorin binding within the myofibrils and determination of its operational apparent affinity constant for Ca2+ at various [free Mg2+] levels. An increase of [free Ca2+] at the outer surface of the SR during the ascending phase of the Ca2+ transient induced further release of Ca2+. In contrast, an increase of [free Ca2+] during the descending phase of the Ca2+ transient did not cause further Ca2+ release. Varying [free H+], [free Mg2+], or the [Na+]/[K+] ratio had no significant effect on the Ca2+ transient during which the modification was applied, but it altered the subsequent Ca2+ transient. Therefore, Ca2+ appears to be the major, if not the only, ion controlling Ca2+ release from the SR rapidly enough to alter a Ca2+ transient during its course. PMID:3981128

Clonality: an R package for testing clonal relatedness of two tumors from the same patient based on their genomic profiles.

PubMed

Ostrovnaya, Irina; Seshan, Venkatraman E; Olshen, Adam B; Begg, Colin B

2011-06-15

If a cancer patient develops multiple tumors, it is sometimes impossible to determine whether these tumors are independent or clonal based solely on pathological characteristics. Investigators have studied how to improve this diagnostic challenge by comparing the presence of loss of heterozygosity (LOH) at selected genetic locations of tumor samples, or by comparing genomewide copy number array profiles. We have previously developed statistical methodology to compare such genomic profiles for an evidence of clonality. We assembled the software for these tests in a new R package called 'Clonality'. For LOH profiles, the package contains significance tests. The analysis of copy number profiles includes a likelihood ratio statistic and reference distribution, as well as an option to produce various plots that summarize the results. Bioconductor (http://bioconductor.org/packages/release/bioc/html/Clonality.html) and http://www.mskcc.org/mskcc/html/13287.cfm.

Multi-unit dosage formulations of theophylline for controlled release applications.

PubMed

Uhumwangho, Michael U; Okor, Roland S

2007-01-01

The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

Designing scattering-free isotropic index profiles using phase-amplitude equations

NASA Astrophysics Data System (ADS)

King, C. G.; Horsley, S. A. R.; Philbin, T. G.

2018-05-01

The Helmholtz equation can be written as coupled equations for the amplitude and phase. By considering spatial phase distributions corresponding to reflectionless wave propagation in the plane and solving for the amplitude in terms of this phase, we designed two-dimensional graded-index media which do not scatter light. We give two illustrative examples, the first of which is a periodic grating for which diffraction is completely suppressed at a single frequency at normal incidence to the periodicity. The second example is a medium which behaves as a "beam shifter" at a single frequency; acting to laterally shift a plane wave, or sufficiently wide beam, without reflection.

In Vivo Release of Vancomycin from Calcium Phosphate Cement.

PubMed

Uchida, Kentaro; Sugo, Ken; Nakajima, Takehiko; Nakawaki, Mitsufumi; Takano, Shotaro; Nagura, Naoshige; Takaso, Masashi; Urabe, Ken

2018-01-01

Calcium phosphate cement (CPC) has good release efficiency and has therefore been used as a drug delivery system for postoperative infection. The release profile of CPC has mainly been evaluated by in vitro studies, which are carried out by immersing test specimens in a relatively large amount of solvent. However, it remains unclear whether antibiotic-impregnated CPC has sufficient clinical effects and release in vivo . We examined the in vivo release profile of CPC impregnated with vancomycin (VCM) and compared this with that of polymethylmethacrylate (PMMA) cement. To evaluate the release profile in vitro , the test specimens were immersed in 10 mL sterile phosphate-buffered saline per gram of test specimen and incubated at 37°C for 56 days in triplicate. For in vivo experiments, the test specimens were implanted between the fascia and muscle of the femur of rats. Residual VCM was extracted from the removed test specimens to determine the amount of VCM released into rat tissues. CPC released more VCM over a longer duration than PMMA in vitro . Released levels of VCM from CPC/VCM in vivo were 3.4-fold, 5.0-fold, and 8.6-fold greater on days 1, 7, and 28, respectively, than those released on the corresponding days from PMMA/VCM and were drastically greater on day 56 due to inefficient release from PMMA/VCM. The amount of VCM released from CPC and PMMA was much higher than the minimum inhibitory concentration (1.56  μ g) and lower than the detection limit, respectively. Our findings suggest that CPC is a suitable material for releasing antibiotics for local action against established postoperative infection.

Metabolic profiling reveals that time related physiological changes in mammalian cell perfusion cultures are bioreactor scale independent.

PubMed

Vernardis, Spyros I; Goudar, Chetan T; Klapa, Maria I

2013-09-01

Metabolic profiling was used to characterize the time course of cell physiology both in laboratory- and manufacturing-scale mammalian cell perfusion cultures. Two independent experiments were performed involving three vials from the same BHK cell bank, used to inoculate three laboratory-scale bioreactors, from which four manufacturing-scale cultures were initiated. It was shown that metabolomic analysis can indeed enhance the prime variable dataset for the monitoring of perfusion cultures by providing a higher resolution view of the metabolic state. Metabolic profiles could capture physiological state shifts over the course of the perfusion cultures and indicated a metabolic "signature" of the phase transitions, which was not observable from prime variable data. Specifically, the vast majority of metabolites had lower concentrations in the middle compared to the other two phases. Notably, metabolomics provided orthogonal (to prime variables) evidence that all cultures followed this same metabolic state shift with cell age, independently of bioreactor scale. © 2013 Elsevier Inc. All rights reserved.

Prediction of Microstructure in HAZ of Welds

NASA Astrophysics Data System (ADS)

Khurana, S. P.; Yancey, R.; Jung, G.

2004-06-01

A modeling technique for predicting microstructure in the heat-affected zone (HAZ) of the hypoeutectoid steels is presented. This technique aims at predicting the phase fractions of ferrite, pearlite, bainite and martensite present in the HAZ after the cool down of a weld. The austenite formation kinetics and austenite decomposition kinetics are calculated using the transient temperature profile. The thermal profile in the weld and the HAZ is calculated by finite-element analysis (FEA). Two kinds of austenite decomposition models are included. The final phase fractions are predicted with the help of a continuous cooling transformation (CCT) diagram of the material. In the calculation of phase fractions either the experimental CCT diagram or the mathematically calculated CCT diagram can be used.

Structural rearrangements preceding dioxygen formation by the water oxidation complex of photosystem II

PubMed Central

Bao, Han; Burnap, Robert L.

2015-01-01

Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II. Recent studies implicate an oxo bridge atom, O5, of the Mn4CaO5 cluster, as the “slowly exchanging” substrate water molecule. The D1-V185N mutant is in close vicinity of O5 and known to extend the lag phase and retard the O2 release phase (slow phase) in this critical last S3+→S0 transition of water oxidation. The pH dependence, hydrogen/deuterium (H/D) isotope effect, and temperature dependence on the O2 release kinetics for this mutant were studied using time-resolved O2 polarography, and comparisons were made with WT and two mutants of the putative proton gate D1-D61. Both kinetic phases in V185N are independent of pH and buffer concentration and have weaker H/D kinetic isotope effects. Each phase is characterized by a parallel or even lower activation enthalpy but a less favorable activation entropy than the WT. The results indicate new rate-determining steps for both phases. It is concluded that the lag does not represent inhibition of proton release but rather, slowing of a previously unrecognized kinetic phase involving a structural rearrangement or tautomerism of the S3+ ground state as it approaches a configuration conducive to dioxygen formation. The parallel impacts on both the lag and O2 formation phases suggest a common origin for the defects surmised to be perturbations of the H-bond network and the water cluster adjacent to O5. PMID:26508637

Studying the thermal/non-thermal crossover in solar flares

NASA Technical Reports Server (NTRS)

Schwartz, R. A.

1994-01-01

This report describes work performed under contract NAS5-32584 for Phase 3 of the Compton Gamma Ray Observatory (CGRO) from 1 November 1993 through 1 November 1994. We have made spectral observations of the hard x-ray and gamma-ray bremsstrahlung emissions from solar flares using the Burst and Transit Source Experiment (BASTE) on CGRO. These measurements of their spectrum and time profile provided valuable information on the fundamental flare processes of energy release, particle acceleration, and energy transport. Our scientific objective was to study both the thermal and non-thermal sources of solar flare hard x-ray and gamma-ray emission.

Developing a new formulation of sodium phenylbutyrate.

PubMed

Guffon, Nathalie; Kibleur, Yves; Copalu, William; Tissen, C; Breitkreutz, Joerg

2012-12-01

Sodium phenylbutyrate (NaPB) is used as a treatment for urea cycle disorders (UCD). However, the available, licensed granule form has an extremely bad taste, which can compromise compliance and metabolic control. A new, taste-masked, coated-granule formulation (Luc 01) under development was characterised for its in vitro taste characteristics, dissolution profiles and bioequivalence compared with the commercial product. Taste, safety and tolerability were also compared in healthy adult volunteers. The in vitro taste profile of NaPB indicated a highly salty and bitter tasting molecule, but Luc 01 released NaPB only after a lag time of ∼10 s followed by a slow release over a few minutes. In contrast, the licensed granules released NaPB immediately. The pharmacokinetic study demonstrated the bioequivalence of a single 5 g dose of the two products in 13 healthy adult volunteers. No statistical difference was seen either for maximal plasma concentration (C(max)) or for area under the plasma concentration-time curve (AUC). CI for C(max) and AUC(0-inf) of NaPB were included in the bioequivalence range of 0.80-1.25. One withdrawal for vomiting and five reports of loss of taste perception (ageusia) were related to the licensed product. Acceptability, bitterness and saltiness assessed immediately after administration indicated a significant preference for Luc 01 (p<0.01), confirming the results of the taste prediction derived from in vitro measurements. In vitro dissolution, in vitro and in vivo taste profiles support the view that the newly developed granules can be swallowed before release of the bitter active substance, thus avoiding stimulation of taste receptors. Moreover, Luc 01 was shown to be bioequivalent to the licensed product. The availability of a taste-masked form should improve compliance which is critical to the efficacy of NaPB treatment in patients with UCD.

Gaseous and particulate emissions from prescribed burning in Georgia.

PubMed

Lee, Sangil; Baumann, Karsten; Schauer, James J; Sheesley, Rebecca J; Naeher, Luke P; Meinardi, Simone; Blake, Donald R; Edgerton, Eric S; Russell, Armistead G; Clements, Mark

2005-12-01

Prescribed burning is a significant source of fine particulate matter (PM2.5) in the southeastern United States. However, limited data exist on the emission characteristics from this source. Various organic and inorganic compounds both in the gas and particle phase were measured in the emissions of prescribed burnings conducted at two pine-dominated forest areas in Georgia. The measurements of volatile organic compounds (VOCs) and PM2.5 allowed the determination of emission factors for the flaming and smoldering stages of prescribed burnings. The VOC emission factors from smoldering were distinctly higher than those from flaming except for ethene, ethyne, and organic nitrate compounds. VOC emission factors show that emissions of certain aromatic compounds and terpenes such as alpha and beta-pinenes, which are important precursors for secondary organic aerosol (SOA), are much higher from active prescribed burnings than from fireplace wood and laboratory open burning studies. Levoglucosan is the major particulate organic compound (POC) emitted for all these studies, though its emission relative to total organic carbon (mg/g OC) differs significantly. Furthermore, cholesterol, an important fingerprint for meat cooking, was observed only in our in situ study indicating a significant release from the soil and soil organisms during open burning. Source apportionment of ambient primary fine particulate OC measured at two urban receptor locations 20-25 km downwind yields 74 +/- 11% during and immediately after the burns using our new in situ profile. In comparison with the previous source profile from laboratory simulations, however, this OC contribution is on average 27 +/- 5% lower.

Two-Phase Eutectic Growth in Al-Cu and Al-Cu-Ag

NASA Astrophysics Data System (ADS)

Senninger, Oriane; Peters, Matthew; Voorhees, Peter W.

2018-02-01

The microstructure developed by two-phase lamellar eutectics (α ) -(θ {-Al}2{Cu}) in Al-Cu and Al-Cu-Ag alloys is analyzed. A model of two-phase eutectic growth in multicomponent alloys is used to determine the scaling law of the eutectic microstructure using the alloy thermophysical properties. The application of the model to these alloys shows that the addition of Ag to Al-Cu alloys does not significantly change the length scale of the microstructure, which is in agreement with previous experimental studies. This is explained by the combined phenomena of the decrease in interface energies with the addition of Ag and the superheating of the (α ) phase interface induced by the Ag composition profile.

Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.

PubMed

Van Bambeke, Françoise

2014-11-01

Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

Controlled release of sulfasalazine release from "smart" pectin gel microspheres under physiological simulated fluids.

PubMed

Costas, Luciana; Pera, Licia M; López, Azucena Gómez; Mechetti, Magdalena; Castro, Guillermo R

2012-07-01

Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255 min in simulated gastric fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

PubMed

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

PubMed

Haugstad, T S; Valø, E T; Langmoen, I A

1995-12-01

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Flavor perception and aroma release from model dairy desserts.

PubMed

Lethuaut, Laurent; Weel, Koen G C; Boelrijk, Alexandra E M; Brossard, Chantal D

2004-06-02

Six model dairy desserts, with three different textures and two sucrose levels, were equally flavored with a blend of four aroma compounds [ethyl pentanoate, amyl acetate, hexanal, and (E)-2-hexenal] and evaluated by a seven person panel in order to study whether the sensory perception of the flavor and the aroma release during eating varied with the textural characteristics or the sweetness intensity of the desserts. The sensory perception was recorded by the time intensity (TI) method, while the in vivo aroma release was simultaneously measured by the MS-nose. Considering the panel as a whole, averaged flavor intensity increased with sucrose level and varied with the texture of the desserts. Depending on the aroma compound, the averaged profile of in vivo aroma release varied, but for each aroma compound, averaged aroma release showed no difference with the sucrose level and little difference with the texture of the desserts. Perceptual sweetness-aroma interactions were the main factors influencing perception whatever the texture of the desserts.

Controlled release of ibuprofen by meso–macroporous silica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.

2014-02-15

Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and releasemore » was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5}0% (black triangles), P84{sub 7}5% (white diamonds), P84{sub 7}5% functionalized by grafting (black squares) and P84{sub 7}5% functionalized by co-condensation method (white triangles). Display Omitted - Highlights: • Ordered meso–macroporous material is used as a controlled delivery system for ibuprofen. • Incorporation of macropores in mesoporous silica improves ibuprofen adsorption. • Meso–macroporous structures provide a lower delivery than mesoporous silica. • APTES functionalization in meso–macroporous materials improves ibuprofen adsorption and delivery behaviour.« less

Laser heterodyne surface profiler

DOEpatents

Sommargren, G.E.

1980-06-16

A method and apparatus are disclosed for testing the deviation of the face of an object from a flat smooth surface using a beam of coherent light of two plane-polarized components, one of a frequency constantly greater than the other by a fixed amount to produce a difference frequency with a constant phase to be used as a reference, and splitting the beam into its two components. The separate components are directed onto spaced apart points on the face of the object to be tested for smoothness while the face of the object is rotated on an axis normal to one point, thereby passing the other component over a circular track on the face of the object. The two components are recombined after reflection to produce a reflected frequency difference of a phase proportional to the difference in path length of one component reflected from one point to the other component reflected from the other point. The phase of the reflected frequency difference is compared with the reference phase to produce a signal proportional to the deviation of the height of the surface along the circular track with respect to the fixed point at the center, thereby to produce a signal that is plotted as a profile of the surface along the circular track. The phase detector includes a quarter-wave plate to convert the components of the reference beam into circularly polarized components, a half-wave plate to shift the phase of the circularly polarized components, and a polarizer to produce a signal of a shifted phase for comparison with the phase of the frequency difference of the reflected components detected through a second polarizer. Rotation of the half-wave plate can be used for phase adjustment over a full 360/sup 0/ range.

Changes in glycolytic enzyme activities in aging erythrocytes fractionated by counter-current distribution in aqueous polymer two-phase systems.

PubMed Central

Jimeno, P; Garcia-Perez, A I; Luque, J; Pinilla, M

1991-01-01

Human and rat erythrocytes were fractionated by counter-current distribution in charge-sensitive dextran/poly(ethylene glycol) two-phase systems. The specific activities of the key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase) declined along the distribution profiles, although the relative positions of the activity profiles were reversed in the two species. These enzymes maintained their normal response to specific regulatory effectors in all cell fractions. No variations were observed for phosphoglycerate kinase and bisphosphoglycerate mutase activities. Some correlations between enzyme activities (pyruvate kinase/hexokinase, pyruvate kinase/phosphofructokinase, pyruvate kinase/pyruvate kinase plus phosphoglycerate kinase, pyruvate kinase/bisphosphoglycerate mutase and phosphoglycerate kinase/bisphosphoglycerate mutase ratios) were studied in whole erythrocyte populations as well as in cell fractions. These results strongly support the fractionation of human erythrocytes according to cell age, as occurs with rat erythrocytes. PMID:1656939