Micro-porous surfaces in controlled drug delivery systems: design and evaluation of diltiazem hydrochloride controlled porosity osmotic pump using non-ionic surfactants as pore-former.

PubMed

Adibkia, Khosro; Ghanbarzadeh, Saeed; Shokri, Mohammad Hosein; Arami, Zahra; Arash, Zeinab; Shokri, Javad

2014-06-01

The major problem associated with conventional drug delivery systems is unpredictable plasma concentrations. The aim of this study was to design a controlled porosity osmotic pump (CPOP) of diltiazem hydrochloride to deliver the drug in a controlled manner. CPOP tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate as semi-permeable membrane. Non-ionic surfactants were applied as pore-formers as well. The effect of pore-formers concentration on the in vitro release of diltiazem was also studied. The formulations were compared based on four comparative parameters, namely, total drug released after 24 h (D24 h), lag-time (tL), squared correlation coefficient of zero order equation (RSQzero) and mean percent deviation from zero order kinetic (MPDzero). Results of scanning electron microscopy studies exhibited formation of pores in the membrane from where the drug release occurred. It was revealed that drug release rate was directly proportional to the concentration of the pore-formers. The value of D24 h in the formulations containing Tween 80 (10%) and Brij 35 (5%) were found to be more than 94.9%, and drug release followed zero order kinetic (RSQzero > 0.99 and MPDzero < 8%) with acceptable tL (lower than 1 h).

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.

IN-VITRO CHARACTERIZATION OF GASTRORETENTIVE MICROBALLOONS PREPARED BY THE EMULSION SOLVENT DIFFUSION METHOD

PubMed Central

Yadav, Akash; Jain, Dinesh Kumar

2010-01-01

Microballoons floatable on JPXIII No.1 solution were developed as a dosage form capable of floating in the stomach. Microballoons were prepared by the emulsion solvent diffusion method using enteric acrylic and other polymers with drug in a mixture of dichloromethane and ethanol. It was found that preparation temperature determined the formation of cavity inside the microsphere and the surface smoothness, determining the floatability and the drug release rate of the microballoons. The correlation between the buoyancy of microballoons and their physical properties, e.g. apparent density and roundness of microballoons were elucidated. The drug loading efficiency of microballoons was also determined. The optimum loading amount of metformin in the microballoons was found to impart ideal floatable properties to the microballoons. By fitting the data into zero order, first order and Highuchi model it was concluded that the release followed zero order release. PMID:22247832

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

PubMed

Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

2016-08-16

Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device.

PubMed

Lance, Kevin D; Good, Samuel D; Mendes, Thaís S; Ishikiriyama, Mynna; Chew, Patrick; Estes, Laurel S; Yamada, Kazuhito; Mudumba, Sri; Bhisitkul, Robert B; Desai, Tejal A

2015-11-01

We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks.

Development of near zero-order release PLGA-based microspheres of a novel antipsychotic.

PubMed

Zhao, Jinlong; Wang, Lexi; Fan, Chunyu; Yu, Kongtong; Liu, Ximing; Zhao, Xiaolei; Wang, Dan; Liu, Wenhua; Su, Zhengxing; Sun, Fengying; Li, Youxin

2017-01-10

The novel antipsychotic isoperidone, a prodrug of paliperidone, was designed to improve liposolubility for the development of poly(D,L-lactide-co-glycolide) (PLGA)-based microspheres to achieve near zero-order release behaviour in vivo. Microspheres with a smooth surface were obtained using the oil-in-water emulsion solvent evaporation method and yielded a high encapsulation efficiency of 92%. Pharmacokinetic studies in beagle dogs showed a one-week plateau phase followed by a two-week quasi-zero-order release with no burst release. The in vitro release method with a good in vitro-in vivo correlation was also established. Pharmacodynamic evaluation was performed using the MK-801-induced schizophrenic behavioural mouse model, and the sustained suppressive effect lasted two weeks. The pharmacokinetic-pharmacodynamic (PK-PD) relationship of isoperidone microspheres was compared to that of oral administration of free drug. The results revealed a strong correlation between the plasma drug level and the antipsychotic effect. A stable drug plasma concentration was detected in mice both intraday and interday from 8 to 22 d after a single injection of isoperidone microspheres, and a sustained suppressive effect on the schizophrenic model was also observed. In comparison, the mouse group receiving oral daily administration exhibited more dose-dependent effects, and the pharmacological effect diminished rapidly in conjunction with a reduction of the plasma drug levels 8h after the last administration of isoperidone on day 3. The above results confirm the superiority of long-acting release over oral administration and indicate a valuable alternative for the clinical treatment of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Development and optimization of buspirone oral osmotic pump tablet

PubMed Central

Derakhshandeh, K.; berenji, M. Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

Development and optimization of buspirone oral osmotic pump tablet.

PubMed

Derakhshandeh, K; Berenji, M Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

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.

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.

In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device

PubMed Central

Lance, Kevin D.; Good, Samuel D.; Mendes, Thaís S.; Ishikiriyama, Mynna; Chew, Patrick; Estes, Laurel S.; Yamada, Kazuhito; Mudumba, Sri; Bhisitkul, Robert B.; Desai, Tejal A.

2015-01-01

Purpose We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. Methods Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. Results In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina–choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. Conclusions Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks. PMID:26559479

Blends of jackfruit seed starch-pectin in the development of mucoadhesive beads containing metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar

2013-11-01

In this work, calcium pectinate-jackfruit (Artocarpus heterophyllus Lam.) seed starch (JFSS) mucoadhesive beads containing metformin HCl were developed through ionotropic-gelation. Effects of pectin and JFSS amounts on drug encapsulation efficiency (DEE), and cumulative drug release after 10 h (R10 h) were optimized using 3(2) factorial design. The optimized calcium pectinate-JFSS beads containing metformin HCl showed DEE of 94.11 ± 3.92%, R10 h of 48.88 ± 2.02%, and mean diameter of 2.06 ± 0.20 mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The pH of test mediums was found critical for swelling and mucoadhesion of these beads. The optimized calcium pectinate-JFSS beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics

PubMed Central

2011-01-01

The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics. PMID:27502639

Release kinetics of papaverine hydrochloride from tablets with different excipients.

PubMed

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

PubMed Central

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

PubMed

Schulze Nahrup, J; Gao, Z M; Mark, J E; Sakr, A

2004-02-11

Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

PubMed

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

Development of extended release dosage forms using non-uniform drug distribution techniques.

PubMed

Huang, Kuo-Kuang; Wang, Da-Peng; Meng, Chung-Ling

2002-05-01

Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37 degrees C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

Sol-gel Derived Warfarin - Silica Composites for Controlled Drug Release.

PubMed

Dolinina, Ekaterina S; Parfenyuk, Elena V

2017-01-01

Warfarin, commonly used anticoagulant in clinic, has serious shortcomings due to its unsatisfactory pharmacodynamics. One of the efficient ways for the improvement of pharmacological and consumer properties of drugs is the development of optimal drug delivery systems. The aim of this work is to synthesize novel warfarin - silica composites and to study in vitro the drug release kinetics to obtain the composites with controlled release. The composites of warfarin with unmodified (UMS) and mercaptopropyl modified silica (MPMS) were synthesized by sol-gel method. The composite formation was confirmed by FTIR spectra. The concentrations of warfarin released to media with pH 1.6, 6.8 and 7.4 were measured using UV spectroscopy. The drug release profiles from the solid composites were described by a series of kinetic models which includes zero order kinetics, first order kinetics, the modified Korsmeyer-Peppas model and Hixson-Crowell model. The synthesized sol-gel composites have different kinetic behavior in the studied media. In contrast to the warfarin composite with unmodified silica, the drug release from the composite with mercaptopropyl modified silica follows zero order kinetics for 24 h irrespective to the release medium pH due to mixed mechanism (duffusion + degradation and/or disintegration of silica matrix). The obtained results showed that warfarin - silica sol-gel composites have a potential application for the development of novel oral formulation of the drug with controlled delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Controlled release of cyclosporine A self-nanoemulsifying systems from osmotic pump tablets: near zero-order release and pharmacokinetics in dogs.

PubMed

Zhang, Xi; Yi, Yueneng; Qi, Jianping; Lu, Yi; Tian, Zhiqiang; Xie, Yunchang; Yuan, Hailong; Wu, Wei

2013-08-16

It is very important to enhance the absorption simultaneously while designing controlled release delivery systems for poorly water-soluble and poorly permeable drugs (BCS IV). In this study, controlled release of cyclosporine (CyA) was achieved by the osmotic release strategy taking advantage of the absorption-enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDSs). The liquid SNEDDS consisting of Labrafil M 1944CS, Transcutol P and Cremophor EL was absorbed by the osmotic tablet core excipients (sucrose, lactose monohydrate, polyethylene oxide, and partly pregelatinized starch) and then transformed into osmotic tablets. Near zero-order release could be achieved for CyA-loaded nanoemulsions reconstituted from the SNEDDS. In general, the influencing factor study indicated that the release rate increased with increase of inner osmotic pressure, ratio of osmotic agent to suspending agent, content of pore-forming agent, and size of release orifice, whereas the thickness of the membrane impeded the release of CyA nanoemulsion. Pharmacokinetic study showed steady blood CyA profiles with prolonged Tmax and MRT, and significantly reduced Cmax for self-nanoemulsifying osmotic pump tablet (SNEOPT) in comparison with highly fluctuating profiles of the core tablet and Sandimmune Neoral(®). However, similar oral bioavailability was observed for either controlled release or non-controlled release formulations. It was concluded that simultaneous controlling on CyA release and absorption-enhancing had been achieved by a combination of osmotic tablet and SNEDDS. Copyright © 2013 Elsevier B.V. All rights reserved.

Modeling transport kinetics in clinoptilolite-phosphate rock systems

NASA Technical Reports Server (NTRS)

Allen, E. R.; Ming, D. W.; Hossner, L. R.; Henninger, D. L.

1995-01-01

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design

PubMed Central

Khatun, Sabera; Sutradhar, Kumar B.

2014-01-01

In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations. PMID:24966835

[Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

PubMed

Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

2015-01-01

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

A novel solubility-modulated granules through porosity osmotic pump for controlled carvedilol delivery.

PubMed

Song, Qun-Li; Li, Ping; Li, Yu-Min

2012-01-01

A method for the preparation of porosity osmotic pump granules was obtained by modulating carvedilol solubility with tartaric acid. Controlled porosity of the membrane was accomplished by the use of pore-forming agent in the coating. In this study, carvedilol was chosen as a model drug with an aim to develop a zero-order release system; tartaric acid was used as the solubility promoter; NaCl was used as the osmotic agent; cellulose acetate (CA) was used as the materials of semipermeable membrane; and PEG-400 was used as the pore-forming agent in the semipermeable membrane. The influence of different factors or levels on the in vitro release was studied. In order to simulate the gastrointestinal tract environments, two kinds of pH media (pH 1.5 and 6.8) on drug release were studied in this research, respectively. This porosity osmotic pump was optimized by single factor design experiments, and it was found to deliver carvedilol at a zero-order rate within 12 h and controlled release for 24 h. We drew a conclusion that the solubility-modulated porosity osmotic pump system is simple to prepare and might be used for the preparation of osmotic pump system of other poorly water-soluble drugs with alkaline or acid groups.

Formulation optimization and evaluation of jackfruit seed starch-alginate mucoadhesive beads of metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar

2013-08-01

The present study deals with the formulation optimization of jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-alginate mucoadhesive beads containing metformin HCl through ionotropic gelation using 3(2) factorial design. The effect of sodium alginate to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release at 10h (R10h, %) was optimized. The optimized beads containing metformin HCl showed DEE of 97.48±3.92%, R10h of 65.70±2.22%, and mean diameter of 1.16±0.11mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads were influenced by pH of the test medium. The optimized beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres.

PubMed

Sivakumar, M; Rao, K Panduranga

2003-05-01

In this work, composite microspheres were prepared from bioactive ceramics such as coralline hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] granules, a biodegradable polymer, sodium alginate, and an antibiotic, gentamicin. Previously, we have shown a gentamicin release from coralline hydroxyapatite granules-chitosan composite microspheres. In the present investigation, we attempted to prepare composite microspheres containing coralline hydroxyapatite granules and sodium alginate by the dispersion polymerization technique with gentamicin incorporated by absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. Fourier transform infrared spectra clearly indicated the presence of per-acid of sodium alginate, phosphate, and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs showed that the composite microspheres were spherical in shape and porous in nature. The particle size of composite microspheres was analyzed, and the average size was found to be 15 microns. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns. Copyright 2003 Wiley Periodicals, Inc.

Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-gelatin composite microspheres.

PubMed

Sivakumar, M; Panduranga Rao, K

2002-08-01

Composite microspheres have been prepared from bioactive ceramics such as coralline hydroxyapatite [CHA, Ca10(PO4)6(OH)2] granules, a biodegradable polymer, gelatin and an antibiotic, gentamicin. In our earlier work, we have shown a gentamicin release from CHA granules--chitosan composite microspheres. In the present investigation, an attempt was made to prepare the composite microspheres containing coralline hydroxyapatite and gelatin (CHA-G), which were prepared by the dispersion polymerization technique and the gentamicin was incorporated by the absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. The Fourier transformed infrared spectrum clearly indicated the presence of amide and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs show that the composite microspheres are spherical in shape and porous in nature. The particle size of composite microspheres was analyzed and the average size was found to be 16 microm. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns.

Release from or through a wax matrix system. IV. Generalized expression of the release process for a reservoir device tablet.

PubMed

Yonezawa, Yorinobu; Ishida, Sumio; Suzuki, Shinobu; Sunada, Hisakazu

2002-09-01

Generalization of the release process through the wax matrix layer was examined by use of a reservoir device tablet. The wax matrix layer of the reservoir device tablet was prepared from a physical mixture of lactose and hydrogenated castor oil to simplify the release properties. Release through the wax matrix layer showed zero-order kinetics in a steady state after a given lag time, and could be divided into two stages. The first stage was the formation process of water channel by dissolving the soluble component in the wax matrix layer. The lag time obtained by applying the square root law equation was well connected with the amount of the matrix layer and mixed weight ratio of components in this layer. The second stage was the zero-order release process of drug in the reservoir through the wax matrix layer, because the effective surface area was fixed. The release rate constants were connected with thickness of the matrix layer and permeability coefficient, and the permeability coefficients were connected with the diffusion coefficient of drug and porosity. Hence the release rate constant could be connected with the amount of matrix layer and the mixed weight ratio of components in the matrix layer. It was therefore suggested that the release process could be generalized using the amount of matrix layer and the mixed weight ratio of components in the matrix layer.

Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine. I. Cellulose acetate as a semipermeable membrane.

PubMed

Makhija, Sapna N; Vavia, Pradeep R

2003-04-14

A controlled porosity osmotic pump-based drug delivery system has been described in this study. Unlike the elementary osmotic pump (EOP) which consists of an osmotic core with the drug surrounded by a semipermeable membrane drilled with a delivery orifice, controlled porosity of the membrane is accomplished by the use of different channeling agents in the coating. The usual dose of pseudoephedrine is 60 mg to be taken three or four times daily. It has a short plasma half life of 5-8 h. Hence, pseudoephedrine was chosen as a model drug with an aim to develop a controlled release system for a period of 12 h. Sodium bicarbonate was used as the osmogent. The effect of different ratios of drug:osmogent on the in-vitro release was studied. Cellulose acetate (CA) was used as the semipermeable membrane. Different channeling agents tried were diethylphthalate (DEP), dibutylphthalate (DBP), dibutylsebacate (DBS) and polyethyleneglycol 400 (PEG 400). The effect of polymer loading on in-vitro drug release was studied. It was found that drug release rate increased with the amount of osmogent due to the increased water uptake, and hence increased driving force for drug release. This could be retarded by the proper choice of channeling agent in order to achieve the desired zero order release profile. Also the lag time seen with tablets coated using diethylphthalate as channeling agent was reduced by using a hydrophilic plasticizer like polyethyleneglycol 400 in combination with diethylphthalate. This system was found to deliver pseudoephedrine at a zero order rate for 12 h. The effect of pH on drug release was also studied. The optimized formulations were subjected to stability studies as per ICH guidelines at different temperature and humidity conditions.

Nano-suspension coating as a technique to modulate the drug release from controlled porosity osmotic pumps for a soluble agent.

PubMed

Bahari, Leila Azharshekoufeh; Javadzadeh, Yousef; Jalali, Mohammad Barzegar; Johari, Peyvand; Nokhodchi, Ali; Shokri, Javad

2017-05-01

In controlled porosity osmotic pumps (CPOP), usually finding a single solvent with a capability to dissolve both film former (hydrophobic) and pore former (hydrophilic) is extremely challenging. Therefore, the aim of the present investigation was to tackle the issue associated with controlled porosity osmotic pump (CPOP) system using nano-suspension coating method. In the present study 4-Amino pyridine was used as a highly water soluble drug. In this method, a hydrophilic pore former (sucrose or mannitol) in nano range was suspended in polymeric coating solution using ball-mill. The performance of the prepared formulations was assessed in terms of D 12h (cumulative release percent after 12h), Dev zero (mean percent deviation of drug release from zero order kinetic), t L (lag time of the drug release) and RSQ zero . The results revealed that gelling agent amount (HPMC E 15LV ) in core and pore former concentration in SPM had crucial effect on SPM integrity. All the optimised formulations showed a burst drug release due to fast dissolving nature of the pore formers. Results obtained from scanning electron microscopy demonstrated the formation of nanopores in the membrane where the drug release takes place via these nanopores. Nano suspension coating method can be introduced as novel method in formulation of CPOPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Topical nanoparticulate formulation of drugs for ocular keratitis

NASA Astrophysics Data System (ADS)

Yang, Xiaoyan

The primary objective of this project is to develop drug-loaded polymeric nanoparticles suspended in a biocompatible gel for topical delivery of therapeutic agents commonly employed in the treatment of ocular viral/bacterial keratitis. PART 1: Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV), D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1) induced viral corneal keratitis. NP containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Cytotoxicity studies suggested that all NP formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases. Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NP are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV. LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells. PART 2: PLGA NP of hydrocortisone butyrate (HB) suspended in thermosensitive PLGA-PEG-PLGA gel were developed for the treatment of bacterial corneal keratitis. Experimental designs were employed in order to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. NP containing HB were prepared by an oil-in-water (O/W) emulsion evaporation technique with different surfactants including polyvinyl alcohol (PVA), pluronic F-108 and chitosan. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels and zero-order release kinetics was observed. Percentage of uptake in HCEC after 4 h was 59.09+/-6.21% for PVA-emulsified NP relative to 55.74+/-6.26% for pluronic-emulsified NP, and 62.54+/-3.30% for chitosan-emulsified NP, respectively. In HCEC cell line, chitosan-emulsified NP with chitosan showed highest cellular uptake efficiency over PVA- and pluronic-emulsified NP. However, NP with chitosan indicated significant cytotoxicity under 200 and 500 ?g/mL after 48 h, while NP with PVA and pluronic showed no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

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.

Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers

PubMed Central

Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin

2018-01-01

Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h. PMID:29565280

Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers.

PubMed

Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin; Yu, Deng-Guang

2018-03-22

Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

Natural gum-type biopolymers as potential modified nonpolar drug release systems.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Moreno, Roger A; Prieto, Vanessa; Recalde, Juanita

2018-06-01

In this work, the relationship between surface properties and drug release mechanism from binary composition tablets formed by quetiapine fumarate and biopolymer materials was studied. The biopolymers correspond to xanthan and tragacanth gums, which are projected as modified drug release systems. The surface studies were carried out by the sessile drop method, while the surface free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical models. On the other hand, the drug release studies were performed by in vitro dissolution tests, where the data were analyzed through kinetic models of zero order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that depending on the type and the proportion of biopolymer, surface properties, and the drug release processes are significantly affected, wherein tragacanth gum present a usual erosion mechanism, while xanthan gum describes a swelling mechanism that controls the release of the drug. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of fenoterol hydrobromide.

PubMed

Elshafeey, Ahmed H; Sami, Elshaimaa I

2008-01-01

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma.

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

PubMed

Liu, Quan; Fassihi, Reza

2008-02-04

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

Drug Release Studies from Caesalpinia pulcherrima Seed Polysaccharide.

PubMed

Jeevanandham, Somasundaram; Dhachinamoorthi, Duraiswamy; Bannoth Chandra Sekhar, Kothapalli

2011-01-01

This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum's (polysaccharide) partial cross-linking had on release of acetaminophen was examined. Applying the exponential equation, the soluble drugs mechanism of release was found to be anomalous. The insoluble drugs showed a near case II or zero order release mechanism. The rate of release in descending order was caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in the release kinetics of the drug was observed on blending with diluents. However, the rate of release varied with the type and amount of blend within the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of drug release decreased upon partial cross-linking and the mechanism of release was found to be of super case II.

Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

PubMed

Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

2017-02-01

The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent.

PubMed

Sakarkar, Dinesh M; Dorle, Avinash K; Mahajan, Nilesh Manoharrao; Sudke, Suresh Gendappa

2013-07-01

The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor (f 1) and similarity factor (f 2) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.

IVABRADINE LOADED SOLID LIPID MICROPARTICLES: FORMULATION, CHARACTERIZATION AND OPTIMIZATION BY CENTRAL COMPOSITE ROTATABLE DESIGN.

PubMed

Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Sher, Muhammad

2017-01-01

The current research focused on improvement of oral bioavailability and decrease in dosing frequency of ivabradine (Iva) in order to enhance patient compliance by formulating novel sustained release Iva loaded solid lipid microparticles (SLMs) with the help of melt emulsification technique. SLMs formulations were designed with the help of three level central composite rotatable design (CCRD) to study the impact of independent variables like lipid concentration, surfactant concentration and stirring speed on responses - percentage yield (Y,) and entrapment efficiency (Y2). Compatibility between the drug and bees wax (BW) was checked by conducting Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). SLMs were further evaluated for rheological behavior, zeta potential, particle size and for morphology by scanning'electron microscope (SEM). The release of drug from SLMs was conducted by USP type-Il apparatus at pH 1.2, pH 6.8 and data were analyzed by different kinetic models like zero order, first order, Higuchi model, Korsmeyer-Peppas and Hixon-Crowell models. The rheo- logical studies approved the good flow behavior of SLMs and spherical smooth surface of SLMs was observed from SEM. DSC, FTIR and XRD studies concluded the lack of any possible interaction between formulation components. The size-of SLMs ranged from 300 to 500 pm and zeta potential study showed the presence of higher negative charge (-30 to -52 mV). Response Y, varied from 53 to 90% and response Y2 ranged from 29 to 78% indicating the effect of formulation variables. The obtained outcomes were analyzed by second order polynomial equation and suggested quadratic model was also validated. SLMs released Iva from 54 to 90% at pH 6.8 and was significantly (p 0.05) affected by BW concentration. The release mechanism followed the zero order and Korsmeyer-Peppas (n 0.85) kinetic models suggesting slow erosion along with diffusion mechanism for Iva release.

Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet.

PubMed

El-Zahaby, Sally A; AbouGhaly, Mohamed H H; Abdelbary, Ghada A; El-Gazayerly, Omaima N

2017-06-08

Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5 mg VNP composed of Maisine™ 35-1, Transcutol ® HP, and Cremophor ® EL was adsorbed on the solid carrier Aeroperl ® . S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel ® , HPMC-K4M, PVP-K30, and Lubripharm ® ), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3 2 *2 1 full factorial design was adopted. The independent variables were: type of coating material (X 1 ), concentration of coating solution (X 2 ), and number of drills (X 3 ). The dependent variables included % release at 2 h (Y 1 ), at 4 h (Y 2 ), and at 8 h (Y 3 ). The in vivo performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry ® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.

Formulation design of an HPMC-based sustained release tablet for pyridostigmine bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution properties.

PubMed

Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

2007-11-01

Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 2(3) full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/- 0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to 1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate.

PubMed

Yang, Xiaoyan; Trinh, Hoang M; Agrahari, Vibhuti; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

2016-04-01

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09 ± 6.21%, 55.74 ± 6.26%, and 62.54 ± 3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Design and characterization of dexamethasone-loaded poly (glycerol sebacate)-poly caprolactone/gelatin scaffold by coaxial electro spinning for soft tissue engineering.

PubMed

Nadim, Afsaneh; Khorasani, Saied Nouri; Kharaziha, Mahshid; Davoodi, Seyyed Mohammadreza

2017-09-01

The aim of this research was to fabricate dexamethasone (Dex)-loaded poly (glycerol sebacate) (PGS)-poly (caprolactone) (PCL)/gelatin (Gt) (PGS-PCL/Gt-Dex) fibrous scaffolds in the form of core/shell structure which have potential application in soft tissues. In this regard, after synthesize and characterizations of PGS, PGS-PCL and gelatin fibrous scaffolds were separately developed in order to optimize the electrospinning parameters. In the next step, coaxial electrospun fibrous scaffold of PGS-PCL/Gt fibrous scaffold with PGS-PCL as core and Gt as shell was developed and its mechanical, physical and chemical properties were characterized. Moreover, degradability, hydrophilicity and biocompatibility of PGS-PCL/Gt fibrous scaffold were evaluated. In addition, Dex was encapsulated in PGS-PCL/Gt fibrous scaffold and drug release was assessed for tissue engineering application. Results demonstrated the formation of coaxial fibrous scaffold with average porosity of 79% and average fiber size of 294nm. Moreover, PGS-PCL/Gt fibrous scaffold revealed lower elastic modulus, ultimate tensile and ultimate elongation than those of PGS-PCL scaffold and more close to mechanical properties of natural tissue. Furthermore, lower contact angle of PGS-PCL/Gt than that of PGS-PCL demonstrated improved surface hydrophilicity of scaffold. DEX release was sustained over a period time of 30days from the scaffolds via three steps consisting of an initial burst release, secondary linear phase release pattern with slower rate over 20days followed by an apparent zero-order release phase. MTT observations demonstrated that there was no evidence of toxicity in the samples with and without Dex. Our findings indicated that core/shell PGS-PCL/Gt-Dex fibrous could be used as a carrier for the sustained release of drugs relevant for tissue engineering which makes it appropriate for soft tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Inlay osmotic pump tablets containing metformin and glipizide.

PubMed

Patel, R B; Patel, G N; Patel, H R; Patel, M M

2011-10-01

The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-β-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G(75%) (75% GLZ release), t(LMET) (lag time of MET release from device), Q(10 h) (percent of MET released within 10 h), and RSQ(ZERO) (R(2) of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompatibility of the platform in vivo.

The effect of excipients on the release kinetics of diclofenac sodium and papaverine hydrochloride from composed tablets.

PubMed

Kasperek, Regina; Trebacz, Hanna; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

For increased analgesic effect, new composed tablets containing diclofenac sodium (DIC) with an addition of papaverine hydrochloride (PAP) were prepared to investigate the mechanism of release of the active substances from tablets with different excipients in eight different formulations. To detect the possible interactions between active substances and excipients differential scanning calorimetry (DSC) was used. A shift of the melting point and enthalpy values of the physical mixtures of tablets components suggested a kind of interaction between components in certain formulations, however, the tabletting process was not disturbed in any of them. Kinetics of drug release from formulations was estimated by zero order, first order and Higuchi and Korsmeyer-Peppas models using results of dissolution of DIC and PAP from tablets. The study revealed that the mechanism of release of active substances was dependent on the excipients contained in tablets and the best fitted kinetics models were obtained for formulations with potentially prolonged release of DIC and PAP.

78 FR 69734 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70881; File No. SR-NSX-2013-20] Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Exchange Rule 11.11 Regarding the Entry and Execution of Zero Display Reserve Orders...

Light diffraction studies of single muscle fibers as a function of fiber rotation.

PubMed Central

Gilliar, W G; Bickel, W S; Bailey, W F

1984-01-01

Light diffraction patterns from single glycerinated frog semitendinosus muscle fibers were examined photographically and photoelectrically as a function of diffraction angle and fiber rotation. The total intensity diffraction pattern indicates that the order maxima change both position and intensity periodically as a function of rotation angle. The total diffracted light, light diffracted above and below the zero-order plane, and light diffracted into individual orders gives information about the fiber's longitudinal and rotational structure and its noncylindrical symmetry. Images FIGURE 2 PMID:6611174

Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines.

PubMed

Ravis, W R; Comerci, C; Ganjam, V K

1986-01-01

Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.

Formulation and evaluation of floating matrix tablet of stavudine

PubMed Central

Prajapati, Pankaj H; Nakum, Vijay V; Patel, Chhagan N

2012-01-01

Background/Aim: The purpose of the study was to prolong the gastric residence time of stavudine by designing its floating tablets and to study the influence of different polymers on its release rate. Materials and Methods: The floating mix matrix tablets of stavudine were prepared by melt granulation method. Beeswax was used as hydrophobic meltable material. Hydroxypropyl methylcellulose (HPMC), sodium bicarbonate, and ethyl cellulose were used as matrixing agent, gas generating agent, and floating enhancer, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, and in vitro drug release. The drug- polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infared (FT-IR). Results: The floating lag time of all the formulations was within the prescribed limit (<3 min). All the formulations showed good matrix integrity and retarded the release of drug for 12 h except the formulation F5.The concentration of beeswax (X1), HPMC K4M (X2), and ethyl cellulose (X3) were selected as independent variables and drug release values at 1 (Q1), at 6 (Q6) and at 12 h (Q12) as dependent variables. Formulation F7 was selected as an optimum formulation as it showed more similarity in dissolution profile with theoretical profile (similarity factor, f2 = 70.91). The dissolution of batch F7 can be described by zero-order kinetics (R2 =0.9936) with anomalous (non-Fickian) diffusion as the release mechanism (n=0.545). There was no difference observed in release profile after temperature sensitivity study at 40°C/75% relative humidity (RH) for 1 month. Conclusion: It can be concluded from this study that the combined mix matrix system containing hydrophobic and hydrophilic polymer minimized the burst release of drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only hydrophilic matrix. PMID:23119237

Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2006-01-01

Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

Formulation and performance characterization of radio-sterilized "progestin-only" microparticles intended for contraception.

PubMed

Puthli, Shivanand; Vavia, Pradeep

2009-01-01

The aim of this study was to formulate and characterize a microparticulate system of progestin-only contraceptive. Another objective was to evaluate the effect of gamma radio-sterilization on in vitro and in vivo drug release characteristics. Levonorgestrel (LNG) microspheres were fabricated using poly(lactide-co-glycolide) (PLGA) by a novel solvent evaporation technique. The formulation was optimized for drug/polymer ratio, emulsifier concentration, and process variables like speed of agitation and evaporation method. The drug to polymer ratio of 1:5 gave the optimum encapsulation efficiency. Speed of agitation influenced the spherical shape of the microparticles, lower speeds yielding less spherical particles. The speed did not have a significant influence on the drug payloads. A combination of stabilizers viz. methyl cellulose and poly vinyl alcohol with in-water solvent evaporation technique yielded microparticles without any free drug crystals on the surface. This aspect significantly eliminated the in vitro dissolution "burst effect". The residual solvent content was well within the regulatory limits. The microparticles passed the test for sterility and absence of pyrogens. In vitro dissolution conducted on the product before and after gamma radiation sterilization at 2.5 Mrad indicated no significant difference in the drug release patterns. The drug release followed zero-order kinetics in both static and agitation conditions of dissolution testing. The in vivo studies conducted in rabbits exhibited LNG release up to 1 month duration with drug levels maintained within the effective therapeutic window.

Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

2014-04-01

Jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-gellan gum (GG) mucoadhesive beads containing metformin HCl were developed through ionotropic gelation technique. The effect of GG to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %) and cumulative drug release at 10h (R10h, %) was optimized and analyzed using response surface methodology based on 3(2) factorial design. The optimized JFSS-GG beads containing metformin HCl showed DEE of 92.67±4.46%, R10h of 61.30±2.37%, and mean diameter of 1.67±0.27 mm. The optimized beads showed pH-dependent swelling and mucoadhesivity with the goat intestinal mucosa. The in vitro drug release from all these JFSS-GG beads containing metformin HCl was followed zero-order pattern (R(2)=0.9907-0.9975) with super case-II transport mechanism over a period of 10 h. The beads were also characterized by SEM and FTIR. The optimized JFSS-GG beads containing metformin HCl exhibited significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and Characterization of a Scalable Microperforated Device Capable of Long-Term Zero Order Drug Release

DTIC Science & Technology

2010-06-29

posterior segment of the eye and include posterior uveitis , age-related macular degeneration, and macular edema (Hsu 2007). Long term drug therapy may be...device for local and controlled delivery of drugs; as a protective carrier to transport labile drugs; and as an implant for treatment of various chronic

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.

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.

Development of Novel Warfarin-Silica Composite for Controlled Drug Release.

PubMed

Parfenyuk, Elena V; Dolinina, Ekaterina S

2017-04-01

The work is devoted to synthesis and study of warfarin composites with unmodified, methyl and phenyl modified silica in order to develop controlled release formulation of the anticoagulant. The composites were prepared by two routes, adsorption and sol-gel, and characterized with FTIR spectroscopy, dynamic light scattering and DSC methods. The drug release behavior from the composites in media with pH 1.6, 6.8 and 7.4 was analyzed in vitro. The release kinetics of the warfarin - silica composites prepared by the two routes was compared among each other and with analogous silica composites with water soluble drug molsidomine. The comparative analysis showed that in general the kinetic regularities and mechanisms of release for both drugs are similar and determined by nonuniform distribution of the drugs over the silica matrixes and stability of the matrixes in the studied media for the adsorbed composites and uniformly distributed drug and more brittle structure for the sol-gel composites. The sol-gel composite of warfarin - phenyl modified silica is perspective for further development of novel warfarin formulation with controlled release because it releases warfarin according to zero-order kinetic law with approximately equal rate in the media imitating different segments of gastrointestinal tract.

Optical phase distribution evaluation by using zero order Generalized Morse Wavelet

NASA Astrophysics Data System (ADS)

Kocahan, Özlem; Elmas, Merve Naz; Durmuş, ćaǧla; Coşkun, Emre; Tiryaki, Erhan; Özder, Serhat

2017-02-01

When determining the phase from the projected fringes by using continuous wavelet transform (CWT), selection of wavelet is an important step. A new wavelet for phase retrieval from the fringe pattern with the spatial carrier frequency in the x direction is presented. As a mother wavelet, zero order generalized Morse wavelet (GMW) is chosen because of the flexible spatial and frequency localization property, and it is exactly analytic. In this study, GMW method is explained and numerical simulations are carried out to show the validity of this technique for finding the phase distributions. Results for the Morlet and Paul wavelets are compared with the results of GMW analysis.

Lessons learned from selective soft-tissue release for gap balancing in primary total knee arthroplasty: an analysis of 1216 consecutive total knee arthroplasties: AAOS exhibit selection.

PubMed

Peters, Christopher L; Jimenez, Chris; Erickson, Jill; Anderson, Mike B; Pelt, Christopher E

2013-10-16

Soft-tissue releases are commonly necessary to achieve symmetrical flexion and extension gaps in primary total knee arthroplasty performed with a measured resection technique. We reviewed the frequency of required releases according to preoperative alignment and the clinical and radiographic results; associations with failure, reoperations, and complications are presented. We reviewed 1216 knees that underwent primary total knee arthroplasty from 2004 to 2009; 774 (64%) were in female patients and 442 (36%), in male patients. In the coronal plane, 855 knees had preoperative varus deformity, 123 were neutral, and 238 had valgus deformity. The mean age at the time of the index procedure was 62.7 years (range, twenty-three to ninety-four years), and the mean body mass index was 32.7 kg/m² (range, 17.4 to 87.9 kg/m²). Clinical outcomes included the Knee Society Score (KSS), implant failure, reoperation, and complications. Radiographs were analyzed for component alignment. The only difference in the total KSS was found at the time of final follow-up between valgus knees with zero releases (total KSS = 178) and those with one or two releases (KSS = 160, p = 0.026). Overall, 407 knees (33.5%) required zero releases, 686 (56.4%) required one or two releases, and 123 (10.1%) required three or more releases. Among varus knees, 37% required zero releases, 55% required one or two releases, and 7.5% required three or more releases. Among neutral knees, 39% required zero releases, 55% required one or two releases, and 5.7% required three or more releases. Only 17% of valgus knees required zero releases whereas 61% required one or two releases and 21.8% required three or more releases. Valgus knees required more releases than neutral or varus knees did (p < 0.001). Selective soft-tissue release for gap balancing in primary total knee arthroplasty is an effective technique that produced excellent clinical and radiographic results regardless of preoperative alignment. Consistent anatomic coronal-plane alignment and soft-tissue balance could be achieved without bone cut modification by using measured bone resection and selective soft-tissue release.

Thermogravimetric analysis for the determination of water release rate from microcrystalline cellulose dry powder and wet bead systems.

PubMed

Mayville, Francis C; Wigent, Rodney J; Schwartz, Joseph B

2006-01-01

The purpose of this work was to determine the total amount of water contained in dry powder and wet bead samples of microcrystalline cellulose, MCC, (Avicel PH-101), taken from various stages of the extrusion/marumerization process used to make beads and to determine the kinetic rates of water release from each sample. These samples were allowed to equilibrate in controlled humidity chambers at 25 degrees C. The total amount of water in each sample, after equilibration, was determined by thermogravimetric analysis (TGA) as a function of temperature. The rates of water release from these samples were determined by using isothermal gravimetric analysis (ITGA) as a function of time. Analysis of the results for these studies suggest that water was released from these systems by several different kinetic mechanisms. The water release mechanisms for these systems include: zero order, second order, and diffusion controlled kinetics. It is believed that all three kinetic mechanisms will occur at the same time, however; only one mechanism will be prominent. The prominent mechanism was based on the amount of water present in the sample.

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.

One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer.

PubMed

Luginbuhl, Kelli M; Schaal, Jeffrey L; Umstead, Bret; Mastria, Eric M; Li, Xinghai; Banskota, Samagya; Arnold, Susan; Feinglos, Mark; D'Alessio, David; Chilkoti, Ashutosh

2017-01-01

Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 receptor has a short half-live owing to enzymatic inactivation and rapid clearance. Here, we show that a subcutaneous depot formed after a single injection of GLP1 recombinantly fused to a thermosensitive elastin-like polypeptide results in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics leads to 10 days of glycemic control in three different mouse models of diabetes, as well as to the reduction of glycosylated hemoglobin levels and weight gain in ob/ob mice treated once weekly for 8 weeks. Our results suggest that the optimized GLP1 formulation could enhance therapeutic outcomes by eliminating peak-and-valley pharmacokinetics and improving overall safety and tolerability. The design principles that we established should be broadly applicable for improving the pharmacological performance of other peptide and protein therapeutics.

Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

PubMed Central

Shah, Kifayat Ullah; Khan, Gul Majid

2012-01-01

The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. PMID:22649325

Babinet’s principle for scalar complex objects in the far field

NASA Astrophysics Data System (ADS)

Rodriguez-Zurita, G.; Rickenstorff, C.; Pastrana-Sánchez, R.; Vázquez-Castillo, J. F.; Robledo-Sanchez, C.; Meneses-Fabian, C.; Toto-Arellano, N. I.

2014-10-01

Babinet’s principle is briefly reviewed, especially regarding the zeroth diffraction order of the far field diffraction pattern associated with a given aperture. The pattern is basically described by the squared modulus of the Fourier transform of its amplitude distribution (scalar case). In this paper, complementary objects are defined with respect to complex values and not only with respect to unity in order to include phase objects and phase modulation. It is shown that the difference in complementary patterns can be sometimes a bright spot at the zero order location as is widely known, but also, it can be a gray spot or even a dark one. Conditions of occurrence for each case are given as well as some numerical and experimental examples.

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

Paranin, V. D.

In work we investigated yttrium iron garnet epitaxial films with a thickness of 10 µm and 55 µm which were grown on the surface of garnet substrate. Using the polarizing microscopy method the branching domain structure of films was shown with the period of domains 21.5 µm and 42.5 µm. Disappearance of domains at presence of an external magnetic field up to 100 Oe was noted. The optical transmission of films for the polarized beam of HeNe laser is investigated and zero diffraction order and odd diffraction rings orders were shown. Interconnection of the period of chaotically oriented domains with angles of axially symmetricmore » diffraction rings orders was shown. Diffraction patterns at various longitudinal magnetic fields are investigated. Disappearance of odd diffraction orders and increasing in intensity of zero diffraction order were fixed. Optical transmission of epitaxial films was measured in range of 500 - 900 nm.« less

Asymmetries in Responses to Attitude Statements: The Example of “Zero-Sum” Beliefs

PubMed Central

Smithson, Michael; Shou, Yiyun

2016-01-01

While much has been written about the consequences of zero-sum (or fixed-pie) beliefs, their measurement has received almost no systematic attention. No researchers, to our awareness, have examined the question of whether the endorsement of a zero-sum-like proposition depends on how the proposition is formed. This paper focuses on this issue, which may also apply to the measurement of other attitudes. Zero-sum statements have a form such as “The more of resource X for consumer A, the less of resource Y for consumer B.” X and Y may be the same resource (such as time), but they can be different (e.g., “The more people commute by bicycle, the less revenue for the city from car parking payments”). These statements have four permutations, and a strict zero-sum believer should regard these four statements as equally valid and therefore should endorse them equally. We find, however, that three asymmetric patterns routinely occur in people's endorsement levels, i.e., clear framing effects, whereby endorsement of one permutation substantially differs from endorsement of another. The patterns seem to arise from beliefs about asymmetric resource flows and power relations between rival consumers. We report three studies, with adult samples representative of populations in two Western and two non-Western cultures, demonstrating that most of the asymmetric belief patterns are consistent across these samples. We conclude with a discussion of the implications of this kind of “order-effect” for attitude measurement. PMID:27445942

Asymmetries in Responses to Attitude Statements: The Example of "Zero-Sum" Beliefs.

PubMed

Smithson, Michael; Shou, Yiyun

2016-01-01

While much has been written about the consequences of zero-sum (or fixed-pie) beliefs, their measurement has received almost no systematic attention. No researchers, to our awareness, have examined the question of whether the endorsement of a zero-sum-like proposition depends on how the proposition is formed. This paper focuses on this issue, which may also apply to the measurement of other attitudes. Zero-sum statements have a form such as "The more of resource X for consumer A, the less of resource Y for consumer B." X and Y may be the same resource (such as time), but they can be different (e.g., "The more people commute by bicycle, the less revenue for the city from car parking payments"). These statements have four permutations, and a strict zero-sum believer should regard these four statements as equally valid and therefore should endorse them equally. We find, however, that three asymmetric patterns routinely occur in people's endorsement levels, i.e., clear framing effects, whereby endorsement of one permutation substantially differs from endorsement of another. The patterns seem to arise from beliefs about asymmetric resource flows and power relations between rival consumers. We report three studies, with adult samples representative of populations in two Western and two non-Western cultures, demonstrating that most of the asymmetric belief patterns are consistent across these samples. We conclude with a discussion of the implications of this kind of "order-effect" for attitude measurement.

Self-interferometric technique for visualization of phase patterns encoded onto a liquid-crystal display

NASA Astrophysics Data System (ADS)

Bentley, Joel B.; Davis, Jeffrey A.; Albero, Jorge; Moreno, Ignacio

2006-10-01

We report a new self-interferometric technique for visualizing phase patterns that are encoded onto a phase-only liquid-crystal display (LCD). In our approach, the LCD generates both the desired object beam as well as the reference beam. Normally the phase patterns are encoded with a phase depth of 2π radians, and all of the incident energy is diffracted into the first-order beam. However, by reducing this phase depth, we can generate an additional zero-order diffracted beam, which acts as the reference beam. We work at distances such that these two patterns spatially interfere, producing an interference pattern that displays the encoded phase pattern. This approach was used recently to display the phase vortices of helical Ince-Gaussian beams. Here we show additional experimental results and analyze the process.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

3D printing of tablets containing multiple drugs with defined release profiles.

PubMed

Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

2015-10-30

We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. Copyright © 2015. Published by Elsevier B.V.

Influence of polymer network parameters of tragacanth gum-based pH responsive hydrogels on drug delivery.

PubMed

Singh, Baljit; Sharma, Vikrant

2014-01-30

The present article deals with design of tragacanth gum-based pH responsive hydrogel drug delivery systems. The characterization of hydrogels has been carried out by SEMs, EDAX, FTIR, (13)C NMR, XRD, TGA/DTA/DTG and swelling studies. The correlation between reaction conditions and structural parameters of polymer networks such as polymer volume fraction in the swollen state (ϕ), Flory-Huggins interaction parameter (χ), molecular weight of the polymer chain between two neighboring cross links (M¯c), crosslink density (ρ) and mesh size (ξ) has been determined. The different kinetic models such as zero order, first order, Higuchi square root law, Korsmeyer-Peppas model and Hixson-Crowell cube root model were applied and it has been observed that release profile of amoxicillin best followed the first order model for the release of drug from the polymer matrix. The swelling of the hydrogels and release of drug from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism in pH 7.4 solution. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biaxially mechanical tuning of 2-D reversible and irreversible surface topologies through simultaneous and sequential wrinkling.

PubMed

Yin, Jie; Yagüe, Jose Luis; Boyce, Mary C; Gleason, Karen K

2014-02-26

Controlled buckling is a facile means of structuring surfaces. The resulting ordered wrinkling topologies provide surface properties and features desired for multifunctional applications. Here, we study the biaxially dynamic tuning of two-dimensional wrinkled micropatterns under cyclic mechanical stretching/releasing/restretching simultaneously or sequentially. A biaxially prestretched PDMS substrate is coated with a stiff polymer deposited by initiated chemical vapor deposition (iCVD). Applying a mechanical release/restretch cycle in two directions loaded simultaneously or sequentially to the wrinkled system results in a variety of dynamic and tunable wrinkled geometries, the evolution of which is investigated using in situ optical profilometry, numerical simulations, and theoretical modeling. Results show that restretching ordered herringbone micropatterns, created through sequential release of biaxial prestrain, leads to reversible and repeatable surface topography. The initial flat surface and the same wrinkled herringbone pattern are obtained alternatively after cyclic release/restretch processes, owing to the highly ordered structure leaving no avenue for trapping irregular topological regions during cycling as further evidenced by the uniformity of strains distributions and negligible residual strain. Conversely, restretching disordered labyrinth micropatterns created through simultaneous release shows an irreversible surface topology whether after sequential or simultaneous restretching due to creation of irregular surface topologies with regions of highly concentrated strain upon formation of the labyrinth which then lead to residual strains and trapped topologies upon cycling; furthermore, these trapped topologies depend upon the subsequent strain histories as well as the cycle. The disordered labyrinth pattern varies after each cyclic release/restretch process, presenting residual shallow patterns instead of achieving a flat state. The ability to dynamically tune the highly ordered herringbone patterning through mechanical stretching or other actuation makes these wrinkles excellent candidates for tunable multifunctional surfaces properties such as reflectivity, friction, anisotropic liquid flow or boundary layer control.

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Abdulhalim, Abdulatif A

2006-01-01

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.

Physicochemical and pharmacological investigation of water/oil microemulsion of non-selective beta blocker for treatment of glaucoma.

PubMed

Hegde, Rahul Rama; Bhattacharya, Shiv Sankar; Verma, Anurag; Ghosh, Amitava

2014-02-01

Ocular drug delivery system always remained associated with lots of difficulties and faced issues of poor drug absorption and poor bioavailability. Timolol maleate is a nonspecific beta blocker used for reduction of elevated intraocular pressure in glaucoma. Timolol maleate is absorbed systemically and is contraindicated in asthmatic patients. This study is focused to deliver Timolol maleate by a water/oil microemulsion to extend the time of reduced intraocular pressure of glaucomatous rabbit's eye measured by using a Schoetz tonometer. The microemulsion is prepared by mixing the oily components with two nonionic surfactants, drug and water, and evaluated for the physicochemical, in vitro and in vivo parameters. The colloidal system demonstrates monodisperse distribution behavior and exhibits a uniform size distribution of finite width. In vitro drug release from microemulsion was found to follow Higuchi's pattern followed by a zero-order drug release by the emulsion. Ex vivo permeation through goat cornea revealed delayed release of Timolol maleate from microemulsion as compared with its aqueous solution. A reduction in intraocular pressure is seen lasting for 12 h compared to aqueous eye drop that lasted for only 5 h. CONCLUSION. In vivo reduction of intraocular pressure revealed a similar efficacy for once daily dosed 0.3% Timolol maleate in microemulsion formulation compared to 0.5% concentration in both microemulsion as well as aqueous formulation. The possible outcome of dose reduction will reduce the cardiovascular side effects generally reported with Timolol maleate eye drops.

Modeling of Phenoxy Acid Herbicide Mineralization and Growth of Microbial Degraders in 15 Soils Monitored by Quantitative Real-Time PCR of the Functional tfdA Gene

PubMed Central

Bælum, Jacob; Prestat, Emmanuel; David, Maude M.; Strobel, Bjarne W.

2012-01-01

Mineralization potentials, rates, and kinetics of the three phenoxy acid (PA) herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), and 2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP), were investigated and compared in 15 soils collected from five continents. The mineralization patterns were fitted by zero/linear or exponential growth forms of the three-half-order models and by logarithmic (log), first-order, or zero-order kinetic models. Prior and subsequent to the mineralization event, tfdA genes were quantified using real-time PCR to estimate the genetic potential for degrading PA in the soils. In 25 of the 45 mineralization scenarios, ∼60% mineralization was observed within 118 days. Elevated concentrations of tfdA in the range 1 × 105 to 5 × 107 gene copies g−1 of soil were observed in soils where mineralization could be described by using growth-linked kinetic models. A clear trend was observed that the mineralization rates of the three PAs occurred in the order 2,4-D > MCPA > MCPP, and a correlation was observed between rapid mineralization and soils exposed to PA previously. Finally, for 2,4-D mineralization, all seven mineralization patterns which were best fitted by the exponential model yielded a higher tfdA gene potential after mineralization had occurred than the three mineralization patterns best fitted by the Lin model. PMID:22635998

[Study on sustained release preparations of Epimedium component].

PubMed

Yan, Hong-mei; Ding, Dong-mei; Zhang, Zhen-hai; Sun, E; Song, Jie; Jia, Xiao-bin

2015-04-01

The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations.

Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

PubMed

Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

2016-04-01

The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. Copyright © 2016 Elsevier B.V. All rights reserved.

Mosquito larvicidal effectiveness of EcoBio-Block S: a novel integrated water-purifying concrete block formulation containing insect growth regulator pyriproxyfen.

PubMed

Kawada, Hitoshi; Saita, Susumu; Shimabukuro, Kozue; Hirano, Masachika; Koga, Masayuki; Iwashita, Toshiaki; Takagi, Masahiro

2006-09-01

EcoBio-Block S, a novel controlled release system (CRS) for the insect growth regulator pyriproxyfen, uses a water-purifying concrete block system (EcoBio-Block) composed of a porous volcanic rock and cement, and it incorporates the aerobic bacterial groups of Bacillus subtilis natto. EcoBio-Block S showed high inhibitory activity against mosquito emergence as well as a water-purifying effect. Chemical analysis and bioassay showed that EcoBio-Block S provides a high-performance CRS that controls the release of pyriproxyfen at low levels according to "zero order kinetics".

Sustained Release of Green Tea Polyphenols from Liposomal Nanoparticles; Release Kinetics and Mathematical Modelling.

PubMed

Prakash Upputuri, Ravi Theaj; Azad Mandal, Abul Kalam

2017-01-01

Background: Green tea polyphenols (GTP) are known to have several health benefits. In spite of these benefits, its application as a therapeutic agent is limited due to some of its limitations such as stability, bioavailability, and biotransformation. To overcome these limitations, liposomal nanoparticles have been used as a carrier of the GTP. Objective: Encapsulation of GTP to the liposomal nanoparticles in order to achieve a sustained release of the GTP and to determine the drug release kinetics and the mechanism of the release. Materials and Methods: GTP encapsulated liposomal nanoparticles were prepared using phosphatidyl choline and cholesterol. The synthesized particles were characterized for their particle size and morphology. In vitro release studies were carried out, followed by drug release kinetics, and determining the mechanism of release. In vitro , antioxidant assay was determined following 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Results: Atomic force microscope (AFM) and high resolution scanning electron microscope (HR SEM) images showed spherical particles of the size of 64.5 and 252 nm. An encapsulation efficiency as high as 77.7% was observed with GTP concentration of 5 mg.mL -1 . In vitro release studies showed that the loading concentrations of GTP were independent to the cumulative percentage of the drug release. GTP release by varying the pH and temperature showed a direct correlation between the release parameter and the percentage of drug release. The higher the pH and temperature, the higher was the percentage of the drug release. The release data showed a good correlation with Zero order kinetics and the mechanism of the release being anomalous mode. Radical scavenging activity of the released GTP showed a potent scavenging activity. Conclusion: GTP encapsulated liposomal nanoparticles could be used as a delivery vehicle for achieving a sustained release.

Dialogue-Games: Meta-Communication Structures for Natural Language Interaction

DTIC Science & Technology

1977-01-01

Dialogue- games are only those described here. For example, they are not necessarily competitive , consciously pursued, or zero-sum. 3. THE DIALOGUE- GAME ...fr«. CO / (Mt l / H- James A. Levin James A. Moore ARPA ORDER NO. 2930 NR 134 374 ISI/RR 77-53 January 1977 Dialogue Games : Meta...these patterns. These patterns have been represented by a set of knowledge structures called Dialogue- games , capturing shared conventional Knowledge

APPLIED ORIGAMI. Origami of thick panels.

PubMed

Chen, Yan; Peng, Rui; You, Zhong

2015-07-24

Origami patterns, including the rigid origami patterns in which flat inflexible sheets are joined by creases, are primarily created for zero-thickness sheets. In order to apply them to fold structures such as roofs, solar panels, and space mirrors, for which thickness cannot be disregarded, various methods have been suggested. However, they generally involve adding materials to or offsetting panels away from the idealized sheet without altering the kinematic model used to simulate folding. We develop a comprehensive kinematic synthesis for rigid origami of thick panels that differs from the existing kinematic model but is capable of reproducing motions identical to that of zero-thickness origami. The approach, proven to be effective for typical origami, can be readily applied to fold real engineering structures. Copyright © 2015, American Association for the Advancement of Science.

Determination of phase from the ridge of CWT using generalized Morse wavelet

NASA Astrophysics Data System (ADS)

Kocahan, Ozlem; Tiryaki, Erhan; Coskun, Emre; Ozder, Serhat

2018-03-01

The selection of wavelet is an important step in order to determine the phase from the fringe patterns. In the present work, a new wavelet for phase retrieval from the ridge of continuous wavelet transform (CWT) is presented. The phase distributions have been extracted from the optical fringe pattern by choosing the zero order generalized morse wavelet (GMW) as a mother wavelet. The aim of the study is to reveal the ways in which the two varying parameters of GMW affect the phase calculation. To show the validity of this method, an experimental study has been conducted by using the diffraction phase microscopy (DPM) setup; consequently, the profiles of red blood cells have been retrieved. The results for the CWT ridge technique with GMW have been compared with the results for the Morlet wavelet and the Paul wavelet; the results are almost identical for Paul and zero order GMW because of their degree of freedom. Also, for further discussion, the Fourier transform and the Stockwell transform have been applied comparatively. The outcome of the comparison reveals that GMWs are highly applicable to the research in various areas, predominantly biomedicine.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

[Study on preparation and release mechanism of effervescent osmotic pump tablet of compound Danshen].

PubMed

Xue, Li'an; Li, Yuanbo; Guo, Dandan; Yin, Jianhua; Liu, Yanchun; Hou, Shixiang

2009-04-01

To prepare effervescent osmotic pump tablet (EOPTs) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen and to study the mechanism of drug released of that tablets. Since compound Danshen consist of compounds with polyphenolic groups or carboxyl groups, such as phenolic acids, flavonoids, and triterpenoids that they were acidic. EOPTs were prepared from tablet cores which containing NaHCO3 as effervescent, NaCL and manitol as osmotic agents, HPMC as retarding agents coating with CA membrane. And study the mechanism of drug released according to the change of tablet osmotic pressure. The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release EOPTs. The drug was completely released from the device with a zero-order release rate over 12 h. EOPTs are Successfully obtained EOPT which the drug is released from the device over 12 h and the release mechanism of EOPTs is explained.

Evaluation and comparison of quantity and pattern of fluoride release from orthodontic adhesives: an in vitro study.

PubMed

Regalla, Ravindra Reddy; Jadav, Chandulal; Babu, Devatha Ashok; Sriram, Roopa Rani S; Sriram, Sanjay Krishna; Kattimani, Vivekanand S

2014-01-01

Orthodontic treatment has gained popularity since beginning of era of dentistry. Now a day, everyone is conscious about their appearance, smile and function. During orthodontic treatment use of brackets and adhesives are common. The bonding of brackets will cause demineralization which requires the fluoridation. So the study has been under- taken to analyze the pattern of fluoride release by commercially available adhesive bonding material for the prevention of demineralization. To evaluate and compare the clinical significance of quantity and pattern of fluoride release from three commercially available adhesives. To assess the pattern of fluoride release and quantity, to reduce the decalcification of enamel around orthodontic brackets and bands during treatment and to prevent further use of topical fluoride both office and self-use agents for prevention of demineralization/for remineralization. The comparison of quantity and pattern of fluoride release study involved commercially available bonding adhesives. They are: Group I--resin reinforced glass Ionomer light cure material (OrthoLC), Group II--fluoride releasing composite resin material (Excel) and Group III--conventional composite (Relay-a-bond) evaluated on 78 freshly extracted premolar teeth divided into three groups consisting 26 specimens in each group. The prepared specimens were stored in artificial saliva at 37°C in an incubator for subsequent fluoride analysis using ORION ion selective electrode coupled with ionalyzer 901. Fluoride analysis made at 24 hours intervals for first 3 consecutive days and thereafter at the end of 10th, 17th, 24th and 31st day of bonding. The data obtained were tabulated and interpreted by statistical analysis using 't' test and one-way analysis of variance (ANOVA). The quantity of fluoride release in groups I and II was significant even at the end of 31st day. The one-way AVOVA showed intra and inter group significance in the quantity of fluoride release. But group III with zero fluoride release with significant decalcification on enamel which requires external use of topical fluorides. The pattern of fluoride released was 3.06 ppm for group I and 2.01 ppm for group II and was declined sharply after 24 hours; and continued to decline in subsequent weeks. Mean quantity of fluoride release by group I was 15.08 ppm were as group II was 9.02 ppm over the test period of 31 days. At the end of 31st day the group I bonding adhesive was releasing considerable amount of fluoride compared to group II whereas group III was nil. At all the periods inter and intra group mean values were highly significant. And group III acted as base line or control group as it was non-fluoride releasing material. Both the fluoride releasing adhesive bond material are useful to reduce the risk of demineralization and further prevent the usage of topical fluoride application and reduce cost and clinical visiting time for both patient and clinician.

The dependence of neuronal encoding efficiency on Hebbian plasticity and homeostatic regulation of neurotransmitter release

PubMed Central

Faghihi, Faramarz; Moustafa, Ahmed A.

2015-01-01

Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively) as words with length equal to three. Then the frequency of each word (here eight words) is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms. This study demonstrates the importance of cooperation of Hebbian mechanism with regulation of neurotransmitter release induced by rapid diffused retrograde messenger in neurons with synapses as low and band-pass filters to obtain high encoding efficiency in different environmental and physiological conditions. PMID:25972786

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Antibiotic release from biodegradable PHBV microparticles.

PubMed

Sendil, D; Gürsel, I; Wise, D L; Hasirci, V

1999-05-20

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

PubMed

Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

2006-11-15

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients incorporated into the IVRs.

Physicochemical characterization of camptothecin membrane binding properties and polymeric microsphere formulations

NASA Astrophysics Data System (ADS)

Selvi, Bilge

In an effort to design novel formulation strategies to optimize the antitumor activity of camptothecin (CPT), the physicochemical and membrane binding properties of the drug, were investigated by various techniques in acidic and physiological pH. The intrinsic solubility of the CPT-lactone free base was determined to be 3.44 muM and 5.11 muM at 22°C and 37°C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for oral absorption. The association constants Kf of the drug for bilayers composed of the zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and the negatively-charged 1,2-dioleoyl-sn-glycero-3-phospho- rac-(1-glycerol) (DOPG) were studied at acidic pH by fluorescence anisotropy and determined to be 35.4 +/- 4.5 M-1 and 93.1 +/- 11.0 M-1 for DOPC and DOPG, respectively, indicating a tendency of CPT to preferentially bind to negatively charged membranes. The energy of activation for the hydrolysis of CPT at physiological pH was found to be 114.3 +/- 33.4 kj/mole. The calculated t½ of the reaction at pH 7.2 at temperatures 25°C and 10°C was found to be 0.07 days and 5.12 days, respectively, whereas the time required for 1% of CPT-lactone to hydrolyze to CPT-carboxylate (t99%) was determined to be 1.8 hours, thus offering enough time to safely handle CPT-lactone at low temperatures. The preformulation results indicated that at highly acidic media CPT is positively charged and exists at its stable lactone form of increased solubility and has a capacity to bind to negatively charged membranes. Taking advantage of the increased stability of CPT in acidic media CPT-loaded microspheres were prepared in a 10 N HCl-methylene chloride mixture using the H-series of poly(D,L-lactide-co-glycolide) (H-PLGA). The system was then compared with a standard microsphere formation method and the results were evaluated with respect to particle morphology and drug release profile. Rough surface of the particles were obtained from the preparation method where a 10 N HCl solution was used. The release pattern of CPT was biphasic comprising a first burst effect followed by zero order release for all the formulations. However, the release of the drug was slightly faster from the microspheres formed with the modified method compared to the standard. Until now clinical application of CPT has been highly restricted by the insolubility and instability of the drug in its active lactone form, resulting in less antitumor potency and poor bioavailability. The pH-dependent release of the CPT-loaded microspheres was also compared and faster initial release (burst phase) was found at neutral pH, whereas at low pH the release was zero order for all the formulations. The results indicate that the stabilization and sustained release of CPT from H-PLGA microspheres might reduce local toxicity while simultaneously prolonging efficiency, suggesting new perspectives in CPT chemotherapy.

Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids.

PubMed

Mhlanga, Nikiwe; Ray, Suprakas Sinha

2015-01-01

For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX), and metal oxide (MO) (titanium dioxide, magnetic iron oxide, and zinc oxide) spheres were synthesised using the solvent-evaporation technique and were tested for sustained drug release. The efficacy of a dosage system is determined by its ability to deliver the drug at a sustained rate, afford an increased plasma half-life, a minimum exposure of toxic drugs to healthy cells and a high drug pay load. Mathematical models were used to elucidate the release mechanism of the drug from the spheres. The release fitted a zero-order model with a correlation coefficient in the range of 0.9878-0.9891 and the release mechanism followed an anomalous release, meaning drug release was afforded through both diffusion and the dissolution of PLA. Therefore, PLA/DOX/MO released the same amount of drug per unit time. Consequently, the potential for PLA use as a carrier was ascertained. Copyright © 2014 Elsevier B.V. All rights reserved.

Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators

NASA Astrophysics Data System (ADS)

Siegel, Ronald A.

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which can permeate through a lipophilic membrane when the drug is uncharged. The second system is based on a nonlinear negative feedback instability that arises from coupling of swelling of a hydrogel membrane to an enzymatic reaction, with the hydrogel controlling access of substrate to the enzyme, and the enzyme's product controlling the hydrogel's swelling state. The latter system, whose autonomous oscillations are driven by glucose at constant external activity, is shown to deliver gonadotropin releasing hormone (GnRH) in rhythmic pulses, with periodicity of the same order as observed in sexually mature adult humans. Relevant experimental results and some mathematical models are reviewed.

Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.

PubMed

Cawello, Willi; Braun, Marina; Andreas, Jens-Otto

2018-01-13

Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.

Plasmonic Lithography Utilizing Epsilon Near Zero Hyperbolic Metamaterial.

PubMed

Chen, Xi; Zhang, Cheng; Yang, Fan; Liang, Gaofeng; Li, Qiaochu; Guo, L Jay

2017-10-24

In this work, a special hyperbolic metamaterial (HMM) metamaterial is investigated for plasmonic lithography of period reduction patterns. It is a type II HMM (ϵ ∥ < 0 and ϵ ⊥ > 0) whose tangential component of the permittivity ϵ ∥ is close to zero. Due to the high anisotropy of the type II epsilon-near-zero (ENZ) HMM, only one plasmonic mode can propagate horizontally with low loss in a waveguide system with ENZ HMM as its core. This work takes the advantage of a type II ENZ HMM composed of aluminum/aluminum oxide films and the associated unusual mode to expose a photoresist layer in a specially designed lithography system. Periodic patterns with a half pitch of 58.3 nm were achieved due to the interference of third-order diffracted light of the grating. The lines were 1/6 of the mask with a period of 700 nm and ∼1/7 of the wavelength of the incident light. Moreover, the theoretical analyses performed are widely applicable to structures made of different materials such as silver as well as systems working at deep ultraviolet wavelengths including 193, 248, and 365 nm.

Anomalous refraction of light through slanted-nanoaperture arrays on metal surface

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

Kim, Myungji; Jung, Yun Suk; Xi, Yonggang

2015-09-07

We report a nanoapertured metal surface that demonstrates anomalous refraction of light for a wide range of incident angles. A nanoslit aperture is designed to serve as a tilted vertical-dipole whose radiation pattern orients to a glancing angle direction to substrate. An array of such slanted nanoslits formed in a metal film redirects an incident beam into the direction of negative refraction angle: the aperture-transmitted wave makes a far-field propagation to the tilt-oriented direction of radiation pattern. The thus-designed nanoaperture array demonstrates the −1st order diffraction (i.e., to the negative refraction-angle direction) with well-suppressed background transmission (the zero-order direct transmissionmore » and other higher-order diffractions). Engineering the radiation pattern of nanoaperture offers an approach to overcoming the limits of conventional diffractive/refractive optics and complementing metasurface-based nano-optics.« less

Apparatus, Method, and Computer Program for a Resolution-Enhanced Pseudo-Noise Code Technique

NASA Technical Reports Server (NTRS)

Li, Steven X. (Inventor)

2015-01-01

An apparatus, method, and computer program for a resolution enhanced pseudo-noise coding technique for 3D imaging is provided. In one embodiment, a pattern generator may generate a plurality of unique patterns for a return to zero signal. A plurality of laser diodes may be configured such that each laser diode transmits the return to zero signal to an object. Each of the return to zero signal includes one unique pattern from the plurality of unique patterns to distinguish each of the transmitted return to zero signals from one another.

Liquid jet impingement normal to a disk in zero gravity. Ph.D. Thesis Toledo Univ.

NASA Technical Reports Server (NTRS)

Labus, T. L.

1977-01-01

The free surface shapes of circular liquid jets impinging normal to sharp-edged disks in zero gravity are determined. Zero gravity drop tower experiments yielded three distinct flow patterns that were classified in terms of the relative effects of surface tension and inertial forces. An order of magnitude analysis was conducted that indicated regions where viscous forces were not significant in the computation of free surface shapes. The free surface analysis was simplified by transforming the governing potential flow equations and boundary conditions into the inverse plane, where the stream function and velocity potential became the coordinates. The resulting nonlinear equations were solved by standard finite difference methods, and comparisons were made with the experimental data for the inertia dominated regime.

Ocean Bottom Pressure Seasonal Cycles and Decadal Trends from GRACE Release-05: Ocean Circulation Implications

NASA Astrophysics Data System (ADS)

Johnson, G. C.; Chambers, D. P.

2013-12-01

Ocean mass variations are important for diagnosing sea level budgets, the hydrological cycle and global energy budget, as well as ocean circulation variability. Here seasonal cycles and decadal trends of ocean mass from January 2003 to December 2012, both global and regional, are analyzed using GRACE Release 05 data. The trend of global flux of mass into the ocean approaches 2 cm decade-1 in equivalent sea level rise. Regional trends are of similar magnitude, with the North Pacific, South Atlantic, and South Indian oceans generally gaining mass and other regions losing mass. These trends suggest a spin-down of the North Pacific western boundary current extension and the Antarctic Circumpolar Current in the South Atlantic and South Indian oceans. The global average seasonal cycle of ocean mass is about 1 cm in amplitude, with a maximum in early October and volume fluxes in and out of the ocean reaching 0.5 Sv (1 Sv = 1 × 106 m3 s-1) when integrated over the area analyzed here. Regional patterns of seasonal ocean mass change have typical amplitudes of 1-4 cm, and include maxima in the subtropics and minima in the subpolar regions in hemispheric winters. The subtropical mass gains and subpolar mass losses in the winter spin up both subtropical and subpolar gyres, hence the western boundary current extensions. Seasonal variations in these currents are order 10 Sv, but since the associated depth-averaged current variations are only order 0.1 cm s-1, they would be difficult to detect using in situ oceanographic instruments. a) Amplitude (colors, in cm) and b) phase (colors, in months of the year) of an annual harmonic fit to monthly GRACE Release 05 CSR 500 km smoothed maps (concurrently with a trend and the semiannual harmonic). The 97.5% confidence interval for difference from zero is also indicated (solid black line). Data within 300 km of coastlines are not considered.

A Drug-Eluting Contact Lens

PubMed Central

Ciolino, Joseph B.; Hoare, Todd R.; Iwata, Naomi G.; Behlau, Irmgard; Dohlman, Claes H.; Langer, Robert; Kohane, Daniel S.

2014-01-01

Purpose To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. Methods Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. Results After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. Conclusions A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications. PMID:19136709

Design and evaluation of hydrophobic coated buoyant core as floating drug delivery system for sustained release of cisapride

PubMed Central

Jacob, Shery; Nair, Anroop B; Patil, Pandurang N

2010-01-01

An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs. PMID:24825997

Accounting for Carbon Dioxide Emissions from Biomass Energy Combustion (released in AEO2010)

EIA Publications

2010-01-01

Carbon Dioxide (CO2) emissions from the combustion of biomass to produce energy are excluded from the energy-related CO2 emissions reported in Annual Energy Outlook 2010. According to current international convention, carbon released through biomass combustion is excluded from reported energy-related emissions. The release of carbon from biomass combustion is assumed to be balanced by the uptake of carbon when the feedstock is grown, resulting in zero net emissions over some period of time]. However, analysts have debated whether increased use of biomass energy may result in a decline in terrestrial carbon stocks, leading to a net positive release of carbon rather than the zero net release assumed by its exclusion from reported energy-related emissions.

Bioerodible System for Sequential Release of Multiple Drugs

PubMed Central

Sundararaj, Sharath C.; Thomas, Mark V.; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

NASA Astrophysics Data System (ADS)

Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

2016-04-01

Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

Coplanar three-beam interference and phase edge dislocations

NASA Astrophysics Data System (ADS)

Patorski, Krzysztof; SłuŻewski, Łukasz; Trusiak, Maciej; Pokorski, Krzysztof

2016-12-01

We present a comprehensive analysis of grating three-beam interference to discover a broad range of the ratio of amplitudes A of +/-1 diffraction orders and the zero order amplitude C providing phase edge dislocations. We derive a condition A/C > 0.5 for the occurrence of phase edge dislocations in three-beam interference self-image planes. In the boundary case A/C = 0.5 singularity conditions are met in those planes (once per interference field period), but the zero amplitude condition is not accompanied by an abrupt phase change. For A/C > 0.5 two adjacent singularities in a single field period show opposite sign topological charges. The occurrence of edge dislocations for selected values of A/C was verified by processing fork fringes obtained by introducing the fourth beam in the plane perpendicular to the one containing three coplanar diffraction orders. Two fork pattern processing methods are described, 2D CWT (two-dimensional continuous wavelet transform) and 2D spatial differentiation.

Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

PubMed

Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

2016-02-08

This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives.

PubMed

Keshavarz, M; Kaffashi, B

2014-12-01

The rheological and drug release behavior of biopolymer nanocomposite gels based on the cellulose derivatives, formulated as the bioadhesive drug delivery platforms, were investigated. The bioadhesive gel is composed of the microcrystalline cellulose, sodium carboxymethyl cellulose and phosphate buffered saline (pH = 7.4 at 20 °C) as the dissolution and release medium. The reinforcing nanofillers such as MMT-clay, fumed porous silica and porous starch were used as additives in the nanogel bioadhesive. The constant steady state viscosities of this nanogels upon incorporation of various nanofillers into the systems is the sign of structural stability. Hence, this system is suitable for use in the controlled drug delivery systems in contact with the biological tissues. Based on the rheological measurements, the shear flow properties (i.e. zero shear viscosity and yield stress) were influenced by the concentration of polymers and nanoparticles. The results indicate that the nonlinear rheological data are fitted properly by the Giesekus model. Furthermore, the results showed that the nonlinear viscoelastic parameters (λ and α) are highly affected by the biogel and nanoparticles concentrations. Finally, the drug release was measured, and the results indicated that the biopolymer-clay nanocomposites have appropriate release pattern as the release is better controlled compared to the other nanogel formulations.

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.

Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

PubMed

Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

2015-07-15

To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

PubMed

Balwierz, Radoslaw; Jankowski, Andrzej; Jasinska, Agata; Marciniak, Dominik; Pluta, Janusz

2016-09-01

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

Colloquium: Zoo of quantum-topological phases of matter

NASA Astrophysics Data System (ADS)

Wen, Xiao-Gang

2017-10-01

What are topological phases of matter? First, they are phases of matter at zero temperature. Second, they have a nonzero energy gap for the excitations above the ground state. Third, they are disordered liquids that seem to have no feature. But those disordered liquids actually can have rich patterns of many-body entanglement representing new kinds of order. This Colloquium gives a simple introduction and a brief survey of topological phases of matter. First topological phases with topological order (i.e., with long-range entanglement) are discussed. Then topological phases without topological order (i.e., with short-range entanglement) are covered.

A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

PubMed

Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

2014-11-01

In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Local tuning of the order parameter in superconducting weak links: A zero-inductance nanodevice

NASA Astrophysics Data System (ADS)

Winik, Roni; Holzman, Itamar; Dalla Torre, Emanuele G.; Buks, Eyal; Ivry, Yachin

2018-03-01

Controlling both the amplitude and the phase of the superconducting quantum order parameter (" separators="|ψ ) in nanostructures is important for next-generation information and communication technologies. The lack of electric resistance in superconductors, which may be advantageous for some technologies, hinders convenient voltage-bias tuning and hence limits the tunability of ψ at the microscopic scale. Here, we demonstrate the local tunability of the phase and amplitude of ψ, obtained by patterning with a single lithography step a Nb nano-superconducting quantum interference device (nano-SQUID) that is biased at its nanobridges. We accompany our experimental results by a semi-classical linearized model that is valid for generic nano-SQUIDs with multiple ports and helps simplify the modelling of non-linear couplings among the Josephson junctions. Our design helped us reveal unusual electric characteristics with effective zero inductance, which is promising for nanoscale magnetic sensing and quantum technologies.

Preparation of acetaminophen capsules containing beads prepared by hot-melt direct blend coating.

PubMed

Pham, Loan; Christensen, John M

2014-02-01

Twelve hydrophobic coating agents were assessed for their effects on drug release after coating sugar cores by a flexible hot-melt coating method using direct blending. Drug-containing pellets were also produced and used as cores. The cores were coated with single or double wax layers containing acetaminophen (APAP). The harder the wax, the slower the resultant drug releases from single-coated beads. Wax coating can be deposited on cores up to 28% of the beads final weight and reaching 58% with wax and drug. Carnauba-coated beads dissolved in approximately 6 h releasing 80% of the loaded drug. Applying another wax layer extended drug release over 20 h, while still delivering 80% of the loaded drug. When drug-containing pellets (33-58% drug loading) were used as cores, double wax-coated pellets exhibited a near zero-order drug release for 16 h, releasing 80% of the loaded drug delivering 18 mg/h. The simple process of hot-melt coating by direct blending of pellet-containing drug-coated formulations provides excellent options for immediate and sustained release formulations when higher lipid coating or drug loading is warranted. Predicted plasma drug concentration time profiles using convolution and in vitro drug release properties of the beads were performed for optimal formulations.

Formulation and In-vitro Evaluation of Tretinoin Microemulsion as a Potential Carrier for Dermal Drug Delivery

PubMed Central

Mortazavi, Seyed Alireza; Pishrochi, Sanaz; Jafari azar, Zahra

2013-01-01

In this study, tretinoin microemulsion has been formulated based on phase diagram studies by changing the amounts and proportions of inactive ingredients, such as surfactants, co-surfactants and oils. The effects of these variables have been determined on microemulsion formation, particle size of the dispersed phase and release profile of tretinoin from microemulsion through dialysis membrane. In released studies, static Franz diffusion cells mounted with dialysis membrane were used. Sampling was conducted every 3 h at room temperature over a period of 24 h. The amount of released drug was measured with UV-spectrophotometer and the percentage of drug released was calculated. Based on the results obtained, the oil phase concentration had a proportional effect on particle size which can consequently influence on drug release. The particle size and the amount of released drug were affected by the applied surfactants. The components of the optimized microemulsion formulation were 15% olive oil, 12% propylene glycol (as co-surfactant), 33% Tween®80 (as surfactant) and 40% distilled water, which was tested for viscosity and rheological behavior. The prepared tretinoin microemulsion showed pseudoplastic-thixotropic behavior. The profile of drug release follows zero order kinetics. The optimized tretinoin microemulsion showed enhanced in-vitro release profile compared to the commercial gels and creams. PMID:24523740

Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

PubMed

Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2014-12-01

Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

Design and in vivo evaluation of carvedilol buccal mucoadhesive patches.

PubMed

Thimmasetty, J; Pandey, G S; Babu, P R Sathesh

2008-07-01

The buccal region offers an attractive route of administration for systemic drug delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral bioavailability is 25-35% because of first pass metabolism. Buccal absorption studies of a carvedilol solution in human volunteers showed 32.86% drug absorption. FTIR and UV spectroscopic methods revealed that there was no interaction between carvedilol and polymers. Carvedilol patches were prepared using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behaviour, tensile strength, and surface pH. In vitro release studies were conducted for carvedilol-loaded patches in phosphate buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. Data of in vitro release from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models used were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas models. In vivo drug release studies in rabbits showed 90.85% of drug release from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among in vitro release and in vivo release of carvedilol was observed.

Formulation and In-vitro Evaluation of Tretinoin Microemulsion as a Potential Carrier for Dermal Drug Delivery.

PubMed

Mortazavi, Seyed Alireza; Pishrochi, Sanaz; Jafari Azar, Zahra

2013-01-01

In this study, tretinoin microemulsion has been formulated based on phase diagram studies by changing the amounts and proportions of inactive ingredients, such as surfactants, co-surfactants and oils. The effects of these variables have been determined on microemulsion formation, particle size of the dispersed phase and release profile of tretinoin from microemulsion through dialysis membrane. In released studies, static Franz diffusion cells mounted with dialysis membrane were used. Sampling was conducted every 3 h at room temperature over a period of 24 h. The amount of released drug was measured with UV-spectrophotometer and the percentage of drug released was calculated. Based on the results obtained, the oil phase concentration had a proportional effect on particle size which can consequently influence on drug release. The particle size and the amount of released drug were affected by the applied surfactants. The components of the optimized microemulsion formulation were 15% olive oil, 12% propylene glycol (as co-surfactant), 33% Tween(®)80 (as surfactant) and 40% distilled water, which was tested for viscosity and rheological behavior. The prepared tretinoin microemulsion showed pseudoplastic-thixotropic behavior. The profile of drug release follows zero order kinetics. The optimized tretinoin microemulsion showed enhanced in-vitro release profile compared to the commercial gels and creams.

Some findings on zero-inflated and hurdle poisson models for disease mapping.

PubMed

Corpas-Burgos, Francisca; García-Donato, Gonzalo; Martinez-Beneito, Miguel A

2018-05-27

Zero excess in the study of geographically referenced mortality data sets has been the focus of considerable attention in the literature, with zero-inflation being the most common procedure to handle this lack of fit. Although hurdle models have also been used in disease mapping studies, their use is more rare. We show in this paper that models using particular treatments of zero excesses are often required for achieving appropriate fits in regular mortality studies since, otherwise, geographical units with low expected counts are oversmoothed. However, as also shown, an indiscriminate treatment of zero excess may be unnecessary and has a problematic implementation. In this regard, we find that naive zero-inflation and hurdle models, without an explicit modeling of the probabilities of zeroes, do not fix zero excesses problems well enough and are clearly unsatisfactory. Results sharply suggest the need for an explicit modeling of the probabilities that should vary across areal units. Unfortunately, these more flexible modeling strategies can easily lead to improper posterior distributions as we prove in several theoretical results. Those procedures have been repeatedly used in the disease mapping literature, and one should bear these issues in mind in order to propose valid models. We finally propose several valid modeling alternatives according to the results mentioned that are suitable for fitting zero excesses. We show that those proposals fix zero excesses problems and correct the mentioned oversmoothing of risks in low populated units depicting geographic patterns more suited to the data. Copyright © 2018 John Wiley & Sons, Ltd.

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

PubMed

Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

2016-01-01

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Flow determination of a pump-turbine at zero discharge

NASA Astrophysics Data System (ADS)

Edinger, G.; Erne, S.; Doujak, E.; Bauer, C.

2014-03-01

When starting up a reversible Francis pump-turbine in pump mode, the machine may operate at zero flow at a given gate opening. Besides reversal flow and prerotation in the draft tube cone, the onset of a fully separated flow in the vaned diffuser is observable at zero- discharge condition. In this paper, the occurrence of prerotation and reversal flow in the conical draft tube and the flow in one stay vane channel of a pump-turbine are examined experimentally and compared to numerical simulations. In order to assess the strongly three-dimensional flow in the stay vane channel, measurements with a 2D laser doppler velocimeter (LDV) were performed at various positions. The inlet flow in the draft tube cone, which becomes significantly at zero discharge in pump mode, is investigated by velocity measurements at two different positions. Pressure fluctuations in the draft tube cone induced by complex flow patterns are also recorded and analyzed. It is found that the swirl number at zero discharge does not significant differ from the values obtained at very low load pumping. Experimental investigations combined with CFD have shown that in the stay vane channel flow velocity components different from zero occur even at no discharge. Streamline plots show the fully separated flow structure.

Optimization and charaterization of repaglinide biodegradable polymeric nanoparticle loaded transdermal patchs: in vitro and in vivo studies.

PubMed

Vijayan, V; Reddy, K Ravindra; Sakthivel, S; Swetha, C

2013-11-01

Biodegradable polymeric nanoparticles loaded Repaglinide were prepared by solvent extraction method. In this method chitosan, PLA and PCL were employed to prepare Repaglinide polymeric nanoparticles. Some of the formulation parameters were optimized to obtain high quality nanoparticles. The particles were spherical shape with sizes of 108.6 ± 3.4 nm to 220.6 ± 1.2 nm and the poly dispersity indexes were in the range of 0.06 to 0.44. The zeta potential was in the range between - 16.48 ± 2.02 and 30.52 ± 3.20 mV. The percentage entrapment efficiency (EE%) was 81.4 ± 1.8% to 92.7 ± 1.4%. The drug release behavior was studied by externally sink method and the release pattern of drug was found to follow zero order, Higuchi and Peppas equations. The optimized PLA-Repaglinide nanoparticles were loaded in Methocel transdermal patches. These transdermal patches were evaluated by physiochemical parameters, in vitro, ex vivo and in vivo studies. Based on in vivo hypoglycemic results, bioavailability parameters like AUC, AUMC, Cmax, Tmax, MRT, t1/2 and relative bioavailability were found to be 2218.88 μIU/mL/h, 381630.3 μIU/mL/h, 41.88 μIU/mL, 36 h, 83.24h, and 52.79 h respectively. The transdermal patch containing Repaglinide nanoparticles showed 76 fold effective than conventional oral administrations. Copyright © 2013 Elsevier B.V. All rights reserved.

3-D loaded scaffolds obtained by supercritical CO2 assisted process

NASA Astrophysics Data System (ADS)

Cardea, S.; Reverchon, E.

2014-08-01

In this work, a supercritical CO2 (SC-CO2) drying process for the formation of 3-D PVDF-HFP loaded scaffolds was tested. Experiments at pressures ranging between 150 and 250 bar and at temperatures ranging between 35 and 55°C were performed. The PVDF-HFP- acetone-ethanol solution at 15% w/w polymer was selected as the base case. The drug (amoxicillin) concentration was varied from 20 to 30% w/w with respect to PVDF-HFP. SC- CO2 drying process was confirmed to be a valid alternative to generate loaded structures; indeed, scaffolds characterized by nanometric networks (with mean pore diameter of about 300 nm) with a homogeneous drug distribution were obtained. Drug controlled release experiments were also performed and a quasi-zero order release kinetic was observed.

Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

PubMed

Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

2013-01-01

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

Removal of water contaminants by nanoscale zero-valent iron immobilized in PAN-based oxidized membrane

NASA Astrophysics Data System (ADS)

Liu, Chunyi; Li, Xiang; Ma, Bomou; Qin, Aiwen; He, Chunju

2014-12-01

The functionalizing nanoporous polyacrylonitrile-based oxidized membrane (PAN-OM) firmly immobilized with highly reactive nanoscale zero-valent iron (NZVI) are successfully prepared via an innovative in situ synthesis method. Due to the formation of ladder structure, the PAN-OM present excellent thermal and chemical stabilities as a new carrier for the in-situ growth of NZVI via firm chelation and reduction action, respectively, which prevent the aggregation and release of NZVI. The developed NZVI-immobilized membrane present effective decolorizing efficiency to both anionic methyl blue and cationic methylene blue with a pseudo-first-order decay and degrading efficiency to trichloroethylene (TCE). The regeneration and stability results show that NZVI-immobilized membrane system can be regenerated without obvious performance reduction, which remain the reactivity after half a year storage period. These results suggest that PAN-based oxidized membrane immobilized with NZVI exhibit significant potential for environmental applications.

Space-variant polarization patterns of non-collinear Poincaré superpositions

NASA Astrophysics Data System (ADS)

Galvez, E. J.; Beach, K.; Zeosky, J. J.; Khajavi, B.

2015-03-01

We present analysis and measurements of the polarization patterns produced by non-collinear superpositions of Laguerre-Gauss spatial modes in orthogonal polarization states, which are known as Poincaré modes. Our findings agree with predictions (I. Freund Opt. Lett. 35, 148-150 (2010)), that superpositions containing a C-point lead to a rotation of the polarization ellipse in 3-dimensions. Here we do imaging polarimetry of superpositions of first- and zero-order spatial modes at relative beam angles of 0-4 arcmin. We find Poincaré-type polarization patterns showing fringes in polarization orientation, but which preserve the polarization-singularity index for all three cases of C-points: lemons, stars and monstars.

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.

Pantoprazole Sodium Loaded Microballoons for the Systemic Approach: In Vitro and In Vivo Evaluation.

PubMed

Gupta, Pravin; Kumar, Manish; Kaushik, Darpan

2017-09-01

Purpose: Various floating and pulsatile drug delivery systems suffer from variations in the gastric transit time affecting the bioavailability of drugs. The objective of the study was to develop Pantoprazole Sodium (PAN) microballoons that may prolong the gastric residence time and could enhance the drug bioavailability. Methods: Microballoons were prepared using Eudragit ® L100 by adopting emulsion solvent diffusion method with non-effervescent approach, in vitro studies were performed and the in vivo evaluation was carried out employing ethanol induced ulceration method. Optimization and validation were carried out through Design Expert ® software. Results: The results demonstrate an increase in percentage yield, buoyancy, encapsulation efficacy and swelling. Particles were in the size range 80-100 µm following zero order release pattern. SEM study revealed their rough surface with spherical shape, internal cavity and porous walls. DSC thermo gram confirms the encapsulation of drug in amorphous form. Significant anti ulcer activity was observed for the prepared microballoons. The calculated ulcer index and protection were 0.20±0.05 and 97.43 % respectively for LRS-O (optimized formulation). Conclusion: This kind of pH dependent drug delivery may provide an efficient dosage regimen with enhanced patient compliance.

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.

A study on the high temperature-dependence of the electrical properties in a solution-deposited zinc-tin-oxide thin-film transistor operated in the saturation region

NASA Astrophysics Data System (ADS)

Yu, Kyeong Min; Bae, Byung Seong; Jung, Myunghee; Yun, Eui-Jung

2016-06-01

We investigate the effects of high temperatures in the range of 292 - 393 K on the electrical properties of solution-processed amorphous zinc-tin-oxide (a-ZTO) thin-film transistors (TFTs) operated in the saturation region. The fabricated a-ZTO TFTs have a non-patterned bottom gate and top contact structure, and they use a heavily-doped Si wafer and SiO2 as a gate electrode and a gate insulator layer, respectively. In a-ZTO TFTs, the trap release energy ( E TR ) was deduced by using Maxwell-Boltzmann statistics. The decreasing E TR toward zero with increasing gate voltage (the density of trap states ( n s )) in the a-ZTO active layer can be attributed to a shift of the Fermi level toward the mobility edge with increasing gate voltage. The TFTs with low gate voltage (low n s ) exhibit multiple trap and release characteristics and show thermally-activated behavior. In TFTs with a high gate voltage (high n s ), however, we observe decreasing mobility and conductivity with increasing temperature at temperatures ranging from 303 to 363 K. This confirms that the E TR can drop to zero, indicating a shift of the Fermi level beyond the mobility edge. Hence, the mobility edge is detected at the cusp between thermally-activated transport and band transport.

NREL and Army Validate Energy Savings for Net Zero Energy Installations |

Science.gov Websites

News | NREL and Army Validate Energy Savings for Net Zero Energy Installations News Release : NREL and Army Validate Energy Savings for Net Zero Energy Installations October 27, 2014 The U.S. Army (Army) has partnered with the Energy Department's National Renewable Energy Laboratory (NREL) to

Eliminating the zero spectrum in Fourier transform profilometry using empirical mode decomposition.

PubMed

Li, Sikun; Su, Xianyu; Chen, Wenjing; Xiang, Liqun

2009-05-01

Empirical mode decomposition is introduced into Fourier transform profilometry to extract the zero spectrum included in the deformed fringe pattern without the need for capturing two fringe patterns with pi phase difference. The fringe pattern is subsequently demodulated using a standard Fourier transform profilometry algorithm. With this method, the deformed fringe pattern is adaptively decomposed into a finite number of intrinsic mode functions that vary from high frequency to low frequency by means of an algorithm referred to as a sifting process. Then the zero spectrum is separated from the high-frequency components effectively. Experiments validate the feasibility of this method.

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.

PubMed

Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Mahmood, Asif; Maheen, Safirah; Afzal, Khurram; Iqbal, Nabila; Andleeb, Mehwish; Abbas, Nazar

2017-12-20

For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Application of halloysite clay nanotubes as a pharmaceutical excipient.

PubMed

Yendluri, Raghuvara; Otto, Daniel P; De Villiers, Melgardt M; Vinokurov, Vladimir; Lvov, Yuri M

2017-04-15

Halloysite nanotubes, a biocompatible nanomaterial of 50-60nm diameter and ca. 15nm lumen, can be used for loading, storage and sustained release of drugs either in its pristine form or with additional polymer complexation for extended release time. This study reports the development composite tablets based on 50wt.% of the drug loaded halloysite mixed with 45wt.% of microcrystalline cellulose. Powder flow and compressibility properties of halloysite (angle of repose, Carr's index, Hausner ratio, Brittle Fracture Index, tensile strength) indicate that halloysite is an excellent tablet excipient. Halloysite tubes can also be filled with nifedipine with ca. 6wt.% loading efficiency and sustained release from the nanotubes. Tablets prepared with drug loaded halloysite allowed for almost zero order nifedipine release for up to 20h. Nifedipine trapped in the nanotubes also protect the drug against light and significantly increased the photostability of the drug. All of these demonstrate that halloysite has the potential to be an excellent pharmaceutical excipient that is also an inexpensive, natural and abundantly available material. Copyright © 2017 Elsevier B.V. All rights reserved.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

PubMed

Bernkop-Schnürch, Andreas; Pinter, Yvonne; Guggi, Davide; Kahlbacher, Hermann; Schöffmann, Gudrun; Schuh, Maximilian; Schmerold, Ivo; Del Curto, Maria Dorly; D'Antonio, Mauro; Esposito, Pierandrea; Huck, Christian

2005-08-18

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Alginate nanoparticles protect ferrous from oxidation: Potential iron delivery system.

PubMed

Katuwavila, Nuwanthi P; Perera, A D L C; Dahanayake, Damayanthi; Karunaratne, V; Amaratunga, Gehan A J; Karunaratne, D Nedra

2016-11-20

A novel, efficient delivery system for iron (Fe 2+ ) was developed using the alginate biopolymer. Iron loaded alginate nanoparticles were synthesized by a controlled ionic gelation method and was characterized with respect to particle size, zeta potential, morphology and encapsulation efficiency. Successful loading was confirmed with Fourier Transform Infrared spectroscopy and Thermogravimetric Analysis. Electron energy loss spectroscopy study corroborated the loading of ferrous into the alginate nanoparticles. Iron encapsulation (70%) was optimized at 0.06% Fe (w/v) leading to the formation of iron loaded alginate nanoparticles with a size range of 15-30nm and with a negative zeta potential (-38mV). The in vitro release studies showed a prolonged release profile for 96h. Release of iron was around 65-70% at pH of 6 and 7.4 whereas it was less than 20% at pH 2.The initial burst release upto 8h followed zero order kinetics at all three pH values. All the release profiles beyond 8h best fitted the Korsmeyer-Peppas model of diffusion. Non Fickian diffusion was observed at pH 6 and 7.4 while at pH 2 Fickian diffusion was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring.

PubMed

Li, Chunxiao; Ning, Meiying; Yao, Xiaodong; Wang, Yankun; Liu, Ying

2016-09-01

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring (IVR) formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80°C for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldn't interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76χ+5.44 (r=0.9998), performing zero-order release at about the target dose of 60 µg/day over 21 days. Drug release increased with temperature elevating from 45 to 55°C, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well.

Phyllotactic arrangements of optical elements

NASA Astrophysics Data System (ADS)

Horacek, M.; Meluzin, P.; Kratky, S.; Matejka, M.; Kolarik, V.

2017-05-01

Phyllotaxy studies arrangements of biological entities, e.g. a placement of seeds in the flower head. Vogel (1979) presented a phyllotactic model based on series of seeds ordered along a primary spiral. This arrangement allows each seed to occupy the same area within a circular flower head. Recently, a similar arrangement of diffraction primitives forming a planar relief diffractive structure was presented. The planar relief structure was used for benchmarking and testing purposes of the electron beam writer patterning process. This contribution presents the analysis of local periods and azimuths of optical phyllotactic arrangements. Two kinds of network characteristic triangles are introduced. If the discussed planar structure has appropriate size and density, diffraction of the incoming light creates characteristic a phyllotactic diffraction pattern. Algorithms enabling the analysis of such behavior were developed and they were validated by fabricated samples of relief structures. Combined and higher diffraction orders are also analyzed. Different approaches enabling the creation of phyllotactic diffractive patterns are proposed. E-beam lithography is a flexible technology for various diffraction gratings origination. The e-beam patterning typically allows for the creation of optical diffraction gratings in the first diffraction order. Nevertheless, this technology enables also more complex grating to be prepared, e.g. blazed gratings and zero order gratings. Moreover, the mentioned kinds of gratings can be combined within one planar relief structure. The practical part of the presented work deals with the nano patterning of such structures by using two different types of the e-beam pattern generators.

An investigation of acetylcholine released in skeletal muscle and protein unbound drug released in blood based on the pyridostigmine bromide (pretreatment drug) sustained-release pellets by microdialysis technique in the rabbit model.

PubMed

Huang, Yuh-Tyng; Cheng, Chun-Jen; Lai, Tsun-Fwu; Tsai, Tong-Rong; Tsai, Tung-Hu; Chuo, Wen-Ho; Cham, Thau-Ming

2007-04-18

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase inhibitor that has been used as a pretreatment drug for "Soman" nerve gas poisoning in combat to increase survival. The once-daily PB-sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods in our laboratory, which was followed by zero-order release mechanism. The results showed that the released concentration of acetylcholine (ACh) in skeletal muscle and the released concentration of protein unbound drug in blood were determined by microdialysis technique to have significant differences (P<0.05) among the three dosage forms (IV injection, commercial IR tablets and the PB-SR pellet). The released concentrations of ACh and protein unbound drug for PB-SR pellets were slower than IV injection and commercial IR tablets; this phenomenon indicating that the retention period of drug efficacy in vivo for PB-SR pellet was longer than the others, that is to say, the PB-SR pellets provided with SR effect in vivo as well. We believe that once-daily administered PB-SR pellets would improve limitations of post-exposure antidotes, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in wars or terrorist attacks in the future.

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.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

Polymer-xerogel composites for controlled release wound dressings.

PubMed

Costache, Marius C; Qu, Haibo; Ducheyne, Paul; Devore, David I

2010-08-01

Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol-gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer-xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings. 2010 Elsevier Ltd. All rights reserved.

Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

PubMed

Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

2017-03-01

Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

Unidimensional factor models imply weaker partial correlations than zero-order correlations.

PubMed

van Bork, Riet; Grasman, Raoul P P P; Waldorp, Lourens J

2018-06-01

In this paper we present a new implication of the unidimensional factor model. We prove that the partial correlation between two observed variables that load on one factor given any subset of other observed variables that load on this factor lies between zero and the zero-order correlation between these two observed variables. We implement this result in an empirical bootstrap test that rejects the unidimensional factor model when partial correlations are identified that are either stronger than the zero-order correlation or have a different sign than the zero-order correlation. We demonstrate the use of the test in an empirical data example with data consisting of fourteen items that measure extraversion.

Construct Demo Input Deck

DTIC Science & Technology

2010-06-01

information diffusion patterns when bridging agents span two otherwise separate groups ? and then how such a simulation would be simulated using ...All users may find it more useful to use the table of contents in order to read sections of interest and reference chain to other parts of the...expression evaluates to 0+20-1 = 19, which would be the end-value expected for a zero-indexed group of twenty agents. Similar calculation can be used to

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Formulation and optimization of pH sensitive drug releasing O/W emulsions using Albizia lebbeck L. seed polysaccharide.

PubMed

Varma, Chekuri Ashok Kumar; Jayaram Kumar, K

2018-04-30

Smart polymers, one of the class of polymers with extensive growth in the last few decades due to their wide applications in drug targeting and controlled delivery systems. With this in mind, the aim of the present study is to design and formulate smart releasing o/w emulsion by using Albizia lebbeck L. seed polysaccharide (ALPS). For this purpose, the physicochemical and drug release characteristics like emulsion capacity (EC), emulsion stability (ES), viscosity, microscopy, zeta potential, polydispersity index (PDI) and in-vitro drug release were performed. The EC and ES values were found to increase with an increased concentration of ALPS. The emulsion formulations were statistically designed by using 3 2 full factorial design. All the emulsions showed a shear-thinning behavior. The zeta potential and polydispersity index were found to be in the range of -35.83 mV to -19.00 mV and 0.232-1.000 respectively. Further, the percent cumulative drug release of the emulsions at 8 h was found to be in the range of 30.19-82.65%. The drug release profile exhibited zero order release kinetics. In conclusion, the ALPS can be used as a natural emulsifier and smart polymer for the preparation of pH sensitive emulsions in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Mechanistic evaluation of alginate-HEC gelisphere compacts for controlled intrastriatal nicotine release in Parkinson's disease.

PubMed

Choonara, Yahya E; Pillay, Viness; Khan, Riaz A; Singh, Neha; du Toit, Lisa C

2009-06-01

This study focused on elucidating a mechanistic understanding in support of the multiple mechanisms which govern the formation of crosslinked alginate-hydroxyethylcellulose (Alg-HEC) gelispheres intended for the controlled intrastriatal release of nicotine as a neuroprotectant in Parkinson's Disease. HEC was incorporated as a reinforcing "protective" colloidal polymer to induce interactions between the free carboxyl groups of alginate with hydroxylated HEC monomers. Gelispheres were compressed within an external poly(lactic-co-glycolic acid) (PLGA) matrix to further prolong the release of nicotine. Sol-gel interconversion mechanisms, matrix deformability moduli, matrix fracture energies and chemometric models of the associated energy paradigms were analyzed for their influence on the mechanism and extent of nicotine release. Textural profiling demonstrated higher fracture energies (7.94-26.69 x 10(-4) J) and lower deformability moduli (12.24-58.36 N/mm) when gelispheres were cured in 2 M HCl as a postcuring step. Ba(2+) crosslinked gelispheres resulted in superiorly compact matrices with an increase in volume of 201-329% as compared to the Ca(2+) and Zn(2+) crosslinked matrices. The order of matrix compactness was as follows: Zn(2+) < Ca(2+) < Ba(2+). Molecular mechanisms of formation, interaction, conversion, and stability of sol-gel transitions depended on the type of crosslinker, crosslinking time, energy transactions, and interactions with molecules of the hydration medium. Ba(2+) crosslinked gelispheres released nicotine slower than Ca(2+) and Zn(2+) crosslinked gelispheres due to the higher energy requirement for interconversion to sol while the energy requirements for Ca(2+) and Zn(2+) was at a lower demand. Ba(2+) crosslinked gelispheres within PLGA matrices therefore retarded nicotine release in a pseudo-zero-order manner over 21 days. (c) 2008 Wiley-Liss, Inc.

Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

PubMed

Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

2015-12-30

Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

Graphene Nanoribbons Fabricated by Helium Ion microscope

NASA Astrophysics Data System (ADS)

Pickard, D.; Oezyilmaz, B.; Thong, J.; Loh, K. P.; Viswanathan, V.; Zhongkai, A.; Mathew, S.; Kundu, T.; Park, C.; Yi, Z.; Xu, X.; Zhang, K.; Tat, T. C.; Wang, H.; Venkatesan, T.; Botton, G.; Couillard, M.

2010-03-01

Graphene, a monolayer graphitic lattice of carbon atoms has tremendous promise for a variety of applications on account of the zero mass of electrons, high mobility and the sensitivity of transport to perturbations at the interface. Patterning graphene is an obvious challenge and mesoscopic devices based on graphene require high spatial resolution patterning that will induce as little damage as possible. We use a helium ion microscope with its 0.4nm spot size beam to directly write patterns on free standing graphene films. TEM images of the patterns reveal holes as small as 4 nm and ribbons with line widths as narrow as 3 nm. The images show recovery of the graphene lattice at a distance of about a nm from the patterned edge. The linewidths of the ribbon can be varied considerably in a controllable fashion over ribbon lengths of the order of microns. . .

Zero-field magnetic response functions in Landau levels

PubMed Central

Gao, Yang; Niu, Qian

2017-01-01

We present a fresh perspective on the Landau level quantization rule; that is, by successively including zero-field magnetic response functions at zero temperature, such as zero-field magnetization and susceptibility, the Onsager’s rule can be corrected order by order. Such a perspective is further reinterpreted as a quantization of the semiclassical electron density in solids. Our theory not only reproduces Onsager’s rule at zeroth order and the Berry phase and magnetic moment correction at first order but also explains the nature of higher-order corrections in a universal way. In applications, those higher-order corrections are expected to curve the linear relation between the level index and the inverse of the magnetic field, as already observed in experiments. Our theory then provides a way to extract the correct value of Berry phase as well as the magnetic susceptibility at zero temperature from Landau level fan diagrams in experiments. Moreover, it can be used theoretically to calculate Landau levels up to second-order accuracy for realistic models. PMID:28655849

Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-10-01

The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

Three-part joint modeling methods for complex functional data mixed with zero-and-one-inflated proportions and zero-inflated continuous outcomes with skewness.

PubMed

Li, Haocheng; Staudenmayer, John; Wang, Tianying; Keadle, Sarah Kozey; Carroll, Raymond J

2018-02-20

We take a functional data approach to longitudinal studies with complex bivariate outcomes. This work is motivated by data from a physical activity study that measured 2 responses over time in 5-minute intervals. One response is the proportion of time active in each interval, a continuous proportions with excess zeros and ones. The other response, energy expenditure rate in the interval, is a continuous variable with excess zeros and skewness. This outcome is complex because there are 3 possible activity patterns in each interval (inactive, partially active, and completely active), and those patterns, which are observed, induce both nonrandom and random associations between the responses. More specifically, the inactive pattern requires a zero value in both the proportion for active behavior and the energy expenditure rate; a partially active pattern means that the proportion of activity is strictly between zero and one and that the energy expenditure rate is greater than zero and likely to be moderate, and the completely active pattern means that the proportion of activity is exactly one, and the energy expenditure rate is greater than zero and likely to be higher. To address these challenges, we propose a 3-part functional data joint modeling approach. The first part is a continuation-ratio model to reorder the ordinal valued 3 activity patterns. The second part models the proportions when they are in interval (0,1). The last component specifies the skewed continuous energy expenditure rate with Box-Cox transformations when they are greater than zero. In this 3-part model, the regression structures are specified as smooth curves measured at various time points with random effects that have a correlation structure. The smoothed random curves for each variable are summarized using a few important principal components, and the association of the 3 longitudinal components is modeled through the association of the principal component scores. The difficulties in handling the ordinal and proportional variables are addressed using a quasi-likelihood type approximation. We develop an efficient algorithm to fit the model that also involves the selection of the number of principal components. The method is applied to physical activity data and is evaluated empirically by a simulation study. Copyright © 2017 John Wiley & Sons, Ltd.

Zero-point energy conservation in classical trajectory simulations: Application to H2CO

NASA Astrophysics Data System (ADS)

Lee, Kin Long Kelvin; Quinn, Mitchell S.; Kolmann, Stephen J.; Kable, Scott H.; Jordan, Meredith J. T.

2018-05-01

A new approach for preventing zero-point energy (ZPE) violation in quasi-classical trajectory (QCT) simulations is presented and applied to H2CO "roaming" reactions. Zero-point energy may be problematic in roaming reactions because they occur at or near bond dissociation thresholds and these channels may be incorrectly open or closed depending on if, or how, ZPE has been treated. Here we run QCT simulations on a "ZPE-corrected" potential energy surface defined as the sum of the molecular potential energy surface (PES) and the global harmonic ZPE surface. Five different harmonic ZPE estimates are examined with four, on average, giving values within 4 kJ/mol—chemical accuracy—for H2CO. The local harmonic ZPE, at arbitrary molecular configurations, is subsequently defined in terms of "projected" Cartesian coordinates and a global ZPE "surface" is constructed using Shepard interpolation. This, combined with a second-order modified Shepard interpolated PES, V, allows us to construct a proof-of-concept ZPE-corrected PES for H2CO, Veff, at no additional computational cost to the PES itself. Both V and Veff are used to model product state distributions from the H + HCO → H2 + CO abstraction reaction, which are shown to reproduce the literature roaming product state distributions. Our ZPE-corrected PES allows all trajectories to be analysed, whereas, in previous simulations, a significant proportion was discarded because of ZPE violation. We find ZPE has little effect on product rotational distributions, validating previous QCT simulations. Running trajectories on V, however, shifts the product kinetic energy release to higher energy than on Veff and classical simulations of kinetic energy release should therefore be viewed with caution.

Permeable reactive barrier of coarse sand-supported zero valent iron for the removal of 2,4-dichlorophenol in groundwater.

PubMed

Gao, Weichun; Zhang, Yongxiang; Zhang, Xiaoye; Duan, Zhilong; Wang, Youhao; Qin, Can; Hu, Xiao; Wang, Hao; Chang, Shan

2015-11-01

In this study, coarse sand-supported zero valent iron (ZVI) composite was synthesized by adding sodium alginate to immobilize. Composite was detected by scanning electron microscope (SEM), X-ray diffraction (XRD), and X-ray fluorescence (XRF). SEM results showed that composite had core-shell structure and a wide porous distribution pattern. The synthesized composite was used for degradation of 2,4-dichlorophenol (2,4-DCP) contamination in groundwater. Experimental results demonstrated that degradation mechanism of 2,4-DCP using coarse sand-supported ZVI included adsorption, desorption, and dechlorination. 2,4-DCP adsorption was described as pseudo-second-order kinetic model. It was concluded that dechlorination was the key reaction pathway, ZVI and hydrogen are prime reductants in dechlorination of 2,4-DCP using ZVI.

Development of a high-resolution automatic digital (urine/electrolytes) flow volume and rate measurement system of miniature size

NASA Technical Reports Server (NTRS)

Liu, F. F.

1975-01-01

To aid in the quantitative analysis of man's physiological rhythms, a flowmeter to measure circadian patterns of electrolyte excretion during various environmental stresses was developed. One initial flowmeter was designed and fabricated, the sensor of which is the approximate size of a wristwatch. The detector section includes a special type of dielectric integrating type sensor which automatically controls, activates, and deactivates the flow sensor data output by determining the presence or absence of fluid flow in the system, including operation under zero-G conditions. The detector also provides qualitative data on the composition of the fluid. A compact electronic system was developed to indicate flow rate as well as total volume per release or the cumulative volume of several releases in digital/analog forms suitable for readout or telemetry. A suitable data readout instrument is also provided. Calibration and statistical analyses of the performance functions required of the flowmeter were also conducted.

A deep convolutional neural network to analyze position averaged convergent beam electron diffraction patterns.

PubMed

Xu, W; LeBeau, J M

2018-05-01

We establish a series of deep convolutional neural networks to automatically analyze position averaged convergent beam electron diffraction patterns. The networks first calibrate the zero-order disk size, center position, and rotation without the need for pretreating the data. With the aligned data, additional networks then measure the sample thickness and tilt. The performance of the network is explored as a function of a variety of variables including thickness, tilt, and dose. A methodology to explore the response of the neural network to various pattern features is also presented. Processing patterns at a rate of  ∼ 0.1 s/pattern, the network is shown to be orders of magnitude faster than a brute force method while maintaining accuracy. The approach is thus suitable for automatically processing big, 4D STEM data. We also discuss the generality of the method to other materials/orientations as well as a hybrid approach that combines the features of the neural network with least squares fitting for even more robust analysis. The source code is available at https://github.com/subangstrom/DeepDiffraction. Copyright © 2018 Elsevier B.V. All rights reserved.

Controlled Electrostatic Self-Assembly of Ibuprofen-Cationic Dextran Nanoconjugates Prepared by low Energy Green Process - a Novel Delivery Tool for Poorly Soluble Drugs.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2015-06-01

The direct effect of electrostatic interaction between ibuprofen and cationic dextran on the system-specific physicochemical parameters and intrinsic dissolution characteristics of ibuprofen was evaluated in order to develop drug-polymer nanoconjugate as a delivery strategy for poorly soluble drugs. Amorphous ibuprofen-DEAE dextran (Ddex) nanoconjugate was prepared using a low energy, controlled amphiphile-polyelectrolyte electrostatic self-assembly technique optimized by ibuprofen critical solubility and Ddex charge screening. Physicochemical characteristics of the nanoconjugates were evaluated using FTIR, DSC, TGA, NMR and SEM relative to pure ibuprofen. The in vitro release profiles and mechanism of ibuprofen release were determined using mathematical models including zero and first order kinetics; Higuchi; Hixson-Crowell and Korsmeyer-Peppas. Electrostatic interaction between ibuprofen and Ddex was confirmed with FT-IR, (1)H NMR and (13)C NMR spectroscopy. The broad and diffused DSC peaks of the nanoconjugate as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. Low concentrations of Ddex up to 1.0 × 10(-6) g/dm(3) enhanced dissolution of ibuprofen to a maximum of 81.32% beyond which retardation occurred steadily. Multiple release mechanisms including diffusion; discrete drug dissolution; anomalous transport and super case II transport were noted. Controlled assembly of ibuprofen and Ddex produced a novel formulation with potential extended drug release dictated by Ddex concentration.

Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

PubMed

Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

2017-07-01

Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.

Stress release structures for actuator beams with a stress gradient

NASA Astrophysics Data System (ADS)

Klaasse, G.; Puers, R.; Tilmans, H. A. C.

2007-10-01

Stress release structures are introduced in fixed-fixed beams or membranes for releasing average stress. The influence of a stress gradient on the initial deformation of a fixed-fixed beam with stress release structures is studied in this paper. The objective is to obtain actuator beams that are insensitive to both the average stress and the stress gradient. The target application for the actuator beam in this study is a surface micromachined variable capacitor with a fixed electrode at the center of the beam. An analytical one-dimensional model is derived which predicts the initial deflection of a fixed-fixed beam with one stress release structure at any location and with two stress release structures, placed symmetrically with respect to the center of the beam at any location. The initial center deflection of the beam with one stress release structure was found from the analytical modeling to be zero for a specific set of parameters, but a negative deflection is always present for this specific configuration, leading to beams that touch the substrate at undesired positions, which implies non-functional devices. The configuration with the two symmetrically placed stress release structures can have zero initial center deflection, according to the analytical model, when the stress release structures are placed at a distance of a quarter of the beam length from the anchor points. Finite-element simulations are performed for both configurations and validate the theory. Deviations from the assumed model result in small initial center deflections, but can be compensated for by a little shift of the stress release structures. Experiments are performed for less ideal configurations with two stress release structures where they are shaped as round meanders. These structures do not fully release the stress and the center deflection therefore depends on the average stress to some extent, as demonstrated by finite element simulations. However, the location can be chosen such that there is an initial center deflection that is close to zero. These experiments are, therefore, in qualitative agreement with the analytical model.

Crossover between Tilt Families and Zero Area Thermal Expansion in Hybrid Prussian Blue Analogues.

PubMed

Phillips, Anthony E; Fortes, A Dominic

2017-12-11

Materials in the family of Prussian blue analogues (C 3 H 5 N 2 ) 2 K[M(CN) 6 ], where C 3 H 5 N 2 is the imidazolium ion and M=Fe, Co, undergo two phase transitions with temperature; at low temperatures the imidazolium cations have an ordered configuration (C2/c), while in the intermediate- and high-temperature phases (both previously reported as R3‾m ) they are dynamically disordered. We show from high-resolution powder neutron diffraction data that the high-temperature phase has zero area thermal expansion in the ab-plane. Supported by Landau theory and single-crystal X-ray diffraction data, we re-evaluate the space group symmetry of the intermediate-temperature phase to R3‾ . This reveals that the low-to-intermediate temperature transition is due to competition between two different tilt patterns of the [M(CN) 6 ] 3- ions. Controlling the relative stabilities of these tilt patterns offers a potential means to tune the exploitable electric behaviour that arises from motion of the imidazolium guest. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction between seed dormancy-release mechanism, environment and seed bank strategy for a widely distributed perennial legume, Parkinsonia aculeata (Caesalpinaceae).

PubMed

Van Klinken, Rieks D; Lukitsch, Bert; Cook, Carly

2008-08-01

Parkinsonia aculeata (Caesalpinaceae) is a perennial legume with seeds that have hard-seeded (physical) dormancy and are potentially very long-lived. Seed dormancy is a characteristic that can both help maximize the probability of seedling establishment and spread the risk of recruitment failure across years (bet-hedging). In this study, dormancy-release patterns are described across the diverse environments in which this species occurs in order to test whether wet heat (incubation under wet, warm-to-hot, conditions) alone can explain those patterns, and in order to determine the likely ecological role of physical dormancy across this species distribution. A seed burial trial was conducted across the full environmental distribution of P. aculeata in Australia (arid to wet-dry tropics, uplands to wetlands, soil surface to 10 cm deep). Wet heat explained the pattern of dormancy release across all environments. Most seeds stored in the laboratory remained dormant throughout the trial (at least 84 %). Dormancy release was quickest for seeds buried during the wet season at relatively high rainfall, upland sites (only 3 % of seeds remained dormant after 35 d). The longest-lived seeds were in wetlands (9 % remained dormant after almost 4 years) and on the soil surface (57 % after 2 years). There was no consistent correlation between increased aridity and rate of dormancy release. The results suggest that physical dormancy in P. aculeata is a mechanism for maximizing seedling establishment rather than a bet-hedging strategy. However, seed persistence can occur in environmental refuges where dormancy-release cues are weak and conditions for germination and establishment are poor (e.g. under dense vegetation or in more arid micro-environments) or unsuitable (e.g. when seeds are inundated or on the soil surface). Risks of recruitment failure in suboptimal environments could therefore be reduced by inter-year fluctuations in microclimate or seed movement.

Development of a novel microemulsion for oral absorption enhancement of all-trans retinoic acid

PubMed Central

Subongkot, Thirapit; Ngawhirunpat, Tanasait

2017-01-01

This study was aimed to develop a novel microemulsion that contained oleth-5 as a surfactant to enhance the oral absorption of all-trans retinoic acid (ATRA). The prepared microemulsion was evaluated for its particle size, shape, zeta potential, in vitro release, in vitro intestinal absorption, intestinal membrane cytotoxicity and stability. The obtained microemulsion was spherical in shape with a particle size of <200 nm and a negative surface charge. The in vitro release of the ATRA-loaded microemulsion was best fit with the zero-order model. This microemulsion significantly improved the intestinal absorption of ATRA. Confocal laser scanning microscopy analysis using a fluorescent dye-loaded microemulsion also confirmed the intestinal absorption result. The intestinal membrane cytotoxicity of the ATRA-loaded microemulsion did not differ from an edible oil (fish oil). Stability testing showed that the ATRA-loaded microemulsion was more stable at 25°C than 40°C. PMID:28831254

Development of a novel microemulsion for oral absorption enhancement of all-trans retinoic acid.

PubMed

Subongkot, Thirapit; Ngawhirunpat, Tanasait

2017-01-01

This study was aimed to develop a novel microemulsion that contained oleth-5 as a surfactant to enhance the oral absorption of all-trans retinoic acid (ATRA). The prepared microemulsion was evaluated for its particle size, shape, zeta potential, in vitro release, in vitro intestinal absorption, intestinal membrane cytotoxicity and stability. The obtained microemulsion was spherical in shape with a particle size of <200 nm and a negative surface charge. The in vitro release of the ATRA-loaded microemulsion was best fit with the zero-order model. This microemulsion significantly improved the intestinal absorption of ATRA. Confocal laser scanning microscopy analysis using a fluorescent dye-loaded microemulsion also confirmed the intestinal absorption result. The intestinal membrane cytotoxicity of the ATRA-loaded microemulsion did not differ from an edible oil (fish oil). Stability testing showed that the ATRA-loaded microemulsion was more stable at 25°C than 40°C.

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating.

PubMed

Alejo, Teresa; Andreu, Vanesa; Mendoza, Gracia; Sebastian, Victor; Arruebo, Manuel

2018-08-01

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system. Copyright © 2018 Elsevier Inc. All rights reserved.

Design and development of hydrogel nanoparticles for mercaptopurine

PubMed Central

Senthil, V.; Kumar, R. Suresh; Nagaraju, C. V. V.; Jawahar, N.; Ganesh, G. N. K.; Gowthamarajan, K.

2010-01-01

Hydrogel nanoparticles have gained attention in recent years as they demonstrate the features and characters of hydrogels and nanoparticles at the same time. In the present study chitosan and carrageenan have been used, as hydrogel nanoparticles of mercaptopurine are developed using natural, biodegradable, and biocompatible polymers like chitosan and carrageenan. As these polymers are hydrophilic in nature, the particles will have a long life span in systemic circulation. Hydrogel nanoparticles with mercaptopurine is form an antileukemia drug by the counter polymer gelation method. Fourier-Transform Infrared (FT-IR) studies have shown a compatibility of polymers with the drug. The diameter of hydrogel nanoparticles was about 370 – 800 nm with a positive zeta potential of 26 – 30 mV. The hydrogel nanoparticles were almost spherical in shape, as revealed by scanning electron microscopy (SEM). Drug loading varied from 9 to 17%. Mercaptopurine released from the nanoparticles at the end of the twenty-fourth hour was about 69.48 – 76.52% at pH 7.4. The drug release from the formulation was following zero order kinetics, which was evident from the release kinetic studies and the mechanism of drug release was anomalous diffusion, which indicated that the drug release was controlled by more than one process. PMID:22247867

The ameliorated longevity and pharmacokinetics of valsartan released from a gel system of ultradeformable vesicles.

PubMed

Ahad, Abdul; Aqil, Mohd; Kohli, Kanchan; Sultana, Yasmin; Mujeeb, Mohd

2016-09-01

The present study traces the development and characterization of the gel formulation of valsartan-loaded ultradeformable vesicles for management of hypertension. The prepared gel formulation of ultradeformable vesicles was evaluated for in vitro skin permeation, release kinetics, skin irritation, pharmacokinetics, and stability. The in vitro skin permeation study showed that the gel formulation of ultradeformable vesicles presented a flux value of 368.74 μg/cm(2)/h, in comparison to that of the traditional liposomal gel formulation, with an enhancement ratio of 26.91, through rat skin. The data for release kinetics showed that the release profile followed zero-order kinetics, and that the drug release mechanism was non-Fickian. The results of the skin irritation study demonstrated that the prepared formulation was safe, less irritant, and well-tolerated for transdermal delivery. The results of the pharmacokinetic study demonstrated that the AUC value of valsartan after transdermal administration was apparently increased. The formulation stored under a refrigerated condition showed greater stability, and results were found to be within the specification under storage conditions. It is evident from this study that the gel formulation of ultradeformable vesicles of valsartan is a promising delivery system for lipophilic drugs, and has reasonably good stability characteristics.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

PubMed

Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

2018-08-01

In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

78 FR 19047 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... Change To Provide the Ability To Prevent Zero Display Reserve Orders From Executing in a Locked Market... Exchange not to execute a Zero Display Reserve Order \\4\\ when the protected bid is equal to the protected offer (i.e., a locked market); (ii) clarify that a Zero Display Reserve Order will be eligible for...

Real-Time and High-Resolution 3D Face Measurement via a Smart Active Optical Sensor.

PubMed

You, Yong; Shen, Yang; Zhang, Guocai; Xing, Xiuwen

2017-03-31

The 3D measuring range and accuracy in traditional active optical sensing, such as Fourier transform profilometry, are influenced by the zero frequency of the captured patterns. The phase-shifting technique is commonly applied to remove the zero component. However, this phase-shifting method must capture several fringe patterns with phase difference, thereby influencing the real-time performance. This study introduces a smart active optical sensor, in which a composite pattern is utilized. The composite pattern efficiently combines several phase-shifting fringes and carrier frequencies. The method can remove zero frequency by using only one pattern. Model face reconstruction and human face measurement were employed to study the validity and feasibility of this method. Results show no distinct decrease in the precision of the novel method unlike the traditional phase-shifting method. The texture mapping technique was utilized to reconstruct a nature-appearance 3D digital face.

Real-Time and High-Resolution 3D Face Measurement via a Smart Active Optical Sensor

PubMed Central

You, Yong; Shen, Yang; Zhang, Guocai; Xing, Xiuwen

2017-01-01

The 3D measuring range and accuracy in traditional active optical sensing, such as Fourier transform profilometry, are influenced by the zero frequency of the captured patterns. The phase-shifting technique is commonly applied to remove the zero component. However, this phase-shifting method must capture several fringe patterns with phase difference, thereby influencing the real-time performance. This study introduces a smart active optical sensor, in which a composite pattern is utilized. The composite pattern efficiently combines several phase-shifting fringes and carrier frequencies. The method can remove zero frequency by using only one pattern. Model face reconstruction and human face measurement were employed to study the validity and feasibility of this method. Results show no distinct decrease in the precision of the novel method unlike the traditional phase-shifting method. The texture mapping technique was utilized to reconstruct a nature-appearance 3D digital face. PMID:28362349

Buried mine detection using fractal geometry analysis to the LWIR successive line scan data image

NASA Astrophysics Data System (ADS)

Araki, Kan

2012-06-01

We have engaged in research on buried mine/IED detection by remote sensing method using LWIR camera. A IR image of a ground, containing buried objects can be assumed as a superimposed pattern including thermal scattering which may depend on the ground surface roughness, vegetation canopy, and effect of the sun light, and radiation due to various heat interaction caused by differences in specific heat, size, and buried depth of the objects and local temperature of their surrounding environment. In this cumbersome environment, we introduce fractal geometry for analyzing from an IR image. Clutter patterns due to these complex elements have oftentimes low ordered fractal dimension of Hausdorff Dimension. On the other hand, the target patterns have its tendency of obtaining higher ordered fractal dimension in terms of Information Dimension. Random Shuffle Surrogate method or Fourier Transform Surrogate method is used to evaluate fractional statistics by applying shuffle of time sequence data or phase of spectrum. Fractal interpolation to each line scan was also applied to improve the signal processing performance in order to evade zero division and enhance information of data. Some results of target extraction by using relationship between low and high ordered fractal dimension are to be presented.

Analytical guidance law development for aerocapture at Mars

NASA Technical Reports Server (NTRS)

Calise, A. J.

1992-01-01

During the first part of this reporting period research has concentrated on performing a detailed evaluation, to zero order, of the guidance algorithm developed in the first period taking the numerical approach developed in the third period. A zero order matched asymptotic expansion (MAE) solution that closely satisfies a set of 6 implicit equations in 6 unknowns to an accuracy of 10(exp -10), was evaluated. Guidance law implementation entails treating the current state as a new initial state and repetitively solving the MAE problem to obtain the feedback controls. A zero order guided solution was evaluated and compared with optimal solution that was obtained by numerical methods. Numerical experience shows that the zero order guided solution is close to optimal solution, and that the zero order MAE outer solution plays a critical role in accounting for the variations in Loh's term near the exit phase of the maneuver. However, the deficiency that remains in several of the critical variables indicates the need for a first order correction. During the second part of this period, methods for computing a first order correction were explored.

Novel swellable polymer of orchidaceae family for gastroretentive drug delivery of famotidine

PubMed Central

Razavi, Mahboubeh; Nyamathulla, Shaik; Karimian, Hamed; Noordin, Mohamed Ibrahim

2014-01-01

This study aimed to develop hydrophilic, gastroretentive matrix tablets of famotidine with good floating and swelling properties. A novel gastroretentive drug delivery formulation was designed using salep, also known as salepi, a flour obtained from grinding dried palmate tubers of Orchis morio var mascula (Orchidaceae family). The main polysaccharide content of salep is glucomannan, highly soluble in cold and hot water, which forms a viscous solution. Salep was characterized for physicochemical properties, thermal stability, chemical interaction, and surface morphology using X-ray diffraction analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Ten different formulations (S1–S10) were prepared using famotidine to salep ratios from 1:0.5 to 1:5. Results demonstrated that all formulations were able to sustain the drug release for more than 24 hours. The S5 formulation, with a famotidine to salep ratio of 1:2.5, had the shortest floating lag time of 35 seconds and 100% drug release within 24 hours. The dissolution data were fitted into popular mathematical models to assess the mechanism of drug release. S5 showed Zero order release (R=0.9746) with Higuchi diffusion (R=0.9428). We conclude that salep, a novel polymer, can be used in controlled release formulations to sustain release for 24 hours, due to inherent swelling and gelling properties. PMID:25246773

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test.

PubMed

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-10-01

To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm(2). The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window.

Bioavailability enhancement of baclofen by gastroretentive floating formulation: statistical optimization, in vitro and in vivo pharmacokinetic studies.

PubMed

Thakar, Krishna; Joshi, Garima; Sawant, Krutika K

2013-06-01

The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS). Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 3(2) factorial design was done using Polyox WSR 303 (X1) and HPMC K4M (X2) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable. Optimized formulation showed floating lag time of 4-5 s, floated for more than 12 h and released the drug in sustained manner. In vitro release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. In vivo floatability study confirmed floatation for more than 6 h. In vivo pharmacokinetic studies in rabbits showed Cmax of 189.96 ± 13.04 ng/mL and Tmax of 4 ± 0.35 h for GFDDS. The difference for AUC(0-T) and AUC(0-∞) between the test and reference formulation was statistically significant (p > 0.05). AUC(0-T) and AUC(0-∞) for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively. GFDDS provided prolonged gastric residence and showed significant increase in bioavailability of baclofen.

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.

Evaluation of zero-order controlled release preparations of nifedipine tablet on dissolution test, together with cost benefit point of view.

PubMed

Sakurai, Miyuki; Naruto, Ikue; Matsuyama, Kenji

2008-05-01

Many generic drugs have been released to decrease medical expenses, but some problems have been reported with regard to bioavailability and safety. In this study, we compared three once-a-day controlled-release preparations of nifedipine by the dissolution test (one branded and two generic preparations). Although the two generic drugs were equivalent to the branded drug according to the criteria listed in the Japanese "Guideline for Bioequivalence Studies of Generic Products", there was still a possibility of problems arising. For example, side effects could be caused by a rapid increase in the blood level of nifedipine with one generic drug, while bioavailability might be inadequate with the other due to its small area under the concentration vs. time curve. When each drug was prescribed at a dosage of 20 mg once daily for two weeks, the difference in the copayment for the patient was only 10 yen. Accordingly, it is important for doctors and pharmacists to carefully consider whether such a slight difference in price is really a benefit for the patient.

Sustained Zero-Order Release of Intact Ultra-Stable Drug-Loaded Liposomes from an Implantable Nanochannel Delivery System

PubMed Central

Celia, Christian; Ferrati, Silvia; Bansal, Shyam; van de Ven, Anne L.; Ruozi, Barbara; Zabre, Erika; Hosali, Sharath; Paolino, Donatella; Sarpietro, Maria Grazia; Fine, Daniel; Fresta, Massimo; Ferrari, Mauro

2014-01-01

Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 hrs, sustaining their constant plasma level for many days is a challenge. To address this, we developed, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib loaded-liposomes, and we demonstrate the release of intact vesicles for over 18 days. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments. PMID:23881575

A novel conditioning process for enhancing dewaterability of waste activated sludge by combination of zero-valent iron and persulfate.

PubMed

Zhou, Xu; Wang, Qilin; Jiang, Guangming; Liu, Peng; Yuan, Zhiguo

2015-06-01

Improvement of sludge dewaterability is crucial for reducing the costs of sludge disposal in wastewater treatment plants. This study presents a novel conditioning method for improving waste activated sludge dewaterability by combination of persulfate and zero-valent iron. The combination of zero-valent iron (0-30g/L) and persulfate (0-6g/L) under neutral pH substantially enhanced the sludge dewaterability due to the advanced oxidization reactions. The highest enhancement of sludge dewaterability was achieved at 4g persulfate/L and 15g zero-valent iron/L, with which the capillary suction time was reduced by over 50%. The release of soluble chemical oxygen demand during the conditioning process implied the decomposition of sludge structure and microorganisms, which facilitated the improvement of dewaterability due to the release of bound water that was included in sludge structure and microorganism. Economic analysis showed that the proposed conditioning process with persulfate and ZVI is more economically favorable for improving WAS dewaterability than classical Fenton reagent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diffraction-analysis-based characterization of very fine gratings

NASA Astrophysics Data System (ADS)

Bischoff, Joerg; Truckenbrodt, Horst; Bauer, Joachim J.

1997-09-01

Fine gratings with spatial periods below one micron, either ruled mechanically or patterned holographically, play a key role as encoders in high precision translational or rotational coordinate or measuring machines. Besides, the fast in-line characterization of submicron patterns is a stringent demand in recent microelectronic technology. Thus, a rapid, destruction free and highly accurate measuring technique is required to ensure the quality during manufacturing and for final testing. We propose an optical method which was already successfully introduced in semiconductor industry. Here, the inverse scatter problem inherent in this diffraction based approach is overcome by sophisticated data analysis such as multivariate regression or neural networks. Shortly sketched, the procedure is as follows: certain diffraction efficiencies are measured with an optical angle resolved scatterometer and assigned to a number of profile parameters via data analysis (prediction). Before, the specific measuring model has to be calibrated. If the wavelength-to-period rate is well below unity, it is quite easy to gather enough diffraction orders. However, for gratings with spatial periods being smaller than the probing wavelength, merely the specular reflex will propagate for perpendicular incidence (zero order grating). Consequently, it is virtually impossible to perform a regression analysis. A proper mean to tackle this bottleneck is to record the zero-order reflex as a function of the incident angle. In this paper, the measurement of submicron gratings is discussed with the examples of 0.8, 1.0 and 1.4 micron period resist gratings on silicon, etched silicon oxide on silicon (same periods) and a 512 nm pitch chromium grating on quartz. Using a He-Ne laser with 633 nm wavelength and measuring the direct reflex in both linear polarizations, it is shown that even submicron patterning processes can be monitored and the resulting profiles with linewidths below a half micron can be characterized reliably with 2(theta) - scatterometry.

Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

NASA Astrophysics Data System (ADS)

Bruno, Giacomo; Geninatti, Thomas; Hood, R. Lyle; Fine, Daniel; Scorrano, Giovanni; Schmulen, Jeffrey; Hosali, Sharath; Ferrari, Mauro; Grattoni, Alessandro

2015-03-01

General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (<=1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (<=1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others.General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (<=1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (<=1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06209d

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

PubMed

Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

2016-11-01

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

PubMed

Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

2015-09-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

PubMed Central

Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

PubMed

Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

2014-01-01

The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

Formulation, characterization, and in vitro/ex vivo evaluation of quercetin-loaded microemulsion for topical application.

PubMed

Kajbafvala, Azar; Salabat, Alireza; Salimi, Anayatollah

2016-12-09

The aim of this study was to develop a new microemulsion formulation for topical application of poorly soluble drug named quercetin. In order to design suitable microemulsion system, the pseudo-ternary phase diagrams of microemulsion systems were constructed at different surfactant/co-surfactant ratios using tween 80 as surfactant, transcutol ® P as a co-surfactant and oleic acid as an oil phase. Some physicochemical properties such as droplet size, density, refractive index, electrical conductivity, pH, surface tension, and viscosity of the microemulsion systems were measured at 298.15 K. The average hydrodynamic droplet size of the optimized microemulsions was obtained by dynamic light scattering method. Morphology assessment of the optimized quercetin-loaded microemulsion by transmission electron microscopy analysis indicated that the particles have the size of about 25 nm and spherical with narrow size distribution. Equilibrium solubility, in vitro drug release at a 24 h time period, release kinetic evaluation as well as ex vivo permeation and retention of quercetin-loaded microemulsions through rat skin has been investigated. The obtained results showed a slow release behavior without any transdermal delivery. Most of the formulations fitted best with zero-order kinetic model with a non-Fickian mechanisms. This study illustrated that the proposed QU-microemulsion has a good potential for use in sunscreen formulations. [Formula: see text].

Nothing to it: Precursors to a Zero Concept in Preschoolers

PubMed Central

Merritt, Dustin J.; Brannon, Elizabeth M.

2013-01-01

Do young children understand the numerical value of empty sets prior to developing a concept of symbolic zero? Are empty sets represented as mental magnitudes? In order to investigate these questions, we tested 4-year old children and adults with a numerical ordering task in which the goal was to select two stimuli in ascending numerical order with occasional empty set stimuli. Both children and adults showed distance effects for empty sets.. Children who were unable to order the symbol zero (e.g., 0 < 1), but who successfully ordered countable integers (e.g., 2 < 4) nevertheless showed distance effects with empty sets. These results suggest that empty sets are represented on the same numerical continuum as non-empty sets and that children represent empty sets numerically prior to understanding symbolic zero. PMID:23219980

Hydrogen production from the dissolution of nano zero valent iron and its effect on anaerobic digestion.

PubMed

Huang, Yu-Xi; Guo, Jialiang; Zhang, Chunyang; Hu, Zhiqiang

2016-01-01

Nano zero valent iron (NZVI) has shown inhibition on methanogenesis in anaerobic digestion due to its reductive decomposition of cell membrane. The inhibition was accompanied by the accumulation of hydrogen gas due to rapid NZVI dissolution. It is not clear whether and how rapid hydrogen release from NZVI dissolution directly affects anaerobic digestion. In this study, the hydrogen release kinetics from NZVI (average size = 55 ± 11 nm) dissolution in deionized water under anaerobic conditions was first evaluated. The first-order NZVI dissolution rate constant was 2.62 ± 0.26 h(-1) with its half-life of 0.26 ± 0.03 h. Two sets of anaerobic digestion experiments (i.e., in the presence of glucose or without any substrate but at different anaerobic sludge concentrations) were performed to study the impact of H2 release from rapid NZVI dissolution, in which H2 was generated in a separate water bottle containing NZVI (i.e., ex situ H2 or externally supplied from NZVI dissolution) before hydrogen gas was introduced to anaerobic digestion. The results showed that the H2 partial pressure in the headspace of the digestion bottle reached as high as 0.27 atm due to rapid NZVI dissolution, resulting in temporary inhibition of methane production. Nevertheless, the 5-d cumulative methane volume in the group with ex situ H2 production due to NZVI dissolution was actually higher than that of control, suggesting NZVI inhibition on methanogenesis is solely due to the reductive decomposition of cell membrane after direct contact with NZVI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development and validation of different methods manipulating zero order and first order spectra for determination of the partially overlapped mixture benazepril and amlodipine: A comparative study

NASA Astrophysics Data System (ADS)

Hemdan, A.

2016-07-01

Three simple, selective, and accurate spectrophotometric methods have been developed and then validated for the analysis of Benazepril (BENZ) and Amlodipine (AML) in bulk powder and pharmaceutical dosage form. The first method is the absorption factor (AF) for zero order and amplitude factor (P-F) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 238 nm or from their first order spectra at 253 nm. The second method is the constant multiplication coupled with constant subtraction (CM-CS) for zero order and successive derivative subtraction-constant multiplication (SDS-CM) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 240 nm and 238 nm, respectively, or from their first order spectra at 214 nm and 253 nm for Benazepril and Amlodipine respectively. The third method is the novel constant multiplication coupled with derivative zero crossing (CM-DZC) which is a stability indicating assay method for determination of Benazepril and Amlodipine in presence of the main degradation product of Benazepril which is Benazeprilate (BENZT). The three methods were validated as per the ICH guidelines and the standard curves were found to be linear in the range of 5-60 μg/mL for Benazepril and 5-30 for Amlodipine, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits.

Development and validation of different methods manipulating zero order and first order spectra for determination of the partially overlapped mixture benazepril and amlodipine: A comparative study.

PubMed

Hemdan, A

2016-07-05

Three simple, selective, and accurate spectrophotometric methods have been developed and then validated for the analysis of Benazepril (BENZ) and Amlodipine (AML) in bulk powder and pharmaceutical dosage form. The first method is the absorption factor (AF) for zero order and amplitude factor (P-F) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 238nm or from their first order spectra at 253nm. The second method is the constant multiplication coupled with constant subtraction (CM-CS) for zero order and successive derivative subtraction-constant multiplication (SDS-CM) for first order spectrum, where both BENZ and AML can be measured from their resolved zero order spectra at 240nm and 238nm, respectively, or from their first order spectra at 214nm and 253nm for Benazepril and Amlodipine respectively. The third method is the novel constant multiplication coupled with derivative zero crossing (CM-DZC) which is a stability indicating assay method for determination of Benazepril and Amlodipine in presence of the main degradation product of Benazepril which is Benazeprilate (BENZT). The three methods were validated as per the ICH guidelines and the standard curves were found to be linear in the range of 5-60μg/mL for Benazepril and 5-30 for Amlodipine, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits. Copyright © 2016 Elsevier B.V. All rights reserved.

Navigation in wood ants Formica japonica: context dependent use of landmarks.

PubMed

Fukushi, Tsukasa; Wehner, Rüdiger

2004-09-01

Wood ants Formica japonica can steer their outbound (foraging) and inbound (homing) courses without using celestial compass information, by relying exclusively on landmark cues. This is shown by training ants to run back and forth between the nest and an artificial feeder, and later displacing the trained ants either from the nest (when starting their foraging runs: outbound full-vector ants) or from the feeder (when starting their home runs: inbound full-vector ants) to various nearby release sites. In addition, ants that have already completed their foraging and homing runs are displaced after arrival either at the feeder (outbound zero-vector ants) or at the nest (inbound zero-vector ants), respectively, to the very same release sites. Upon release, the full-vector ants steer their straight courses by referring to panoramic landmark cues, while the zero-vector ants presented with the very same visual scenery immediately search for local landmark cues defining their final goal. Hence, it depends on the context, in this case on the state of the forager's round-trip cycle, what visual cues are picked out from a given set of landmarks and used for navigation.

Power selective optical filter devices and optical systems using same

DOEpatents

Koplow, Jeffrey P

2014-10-07

In an embodiment, a power selective optical filter device includes an input polarizer for selectively transmitting an input signal. The device includes a wave-plate structure positioned to receive the input signal, which includes at least one substantially zero-order, zero-wave plate. The zero-order, zero-wave plate is configured to alter a polarization state of the input signal passing in a manner that depends on the power of the input signal. The zero-order, zero-wave plate includes an entry and exit wave plate each having a fast axis, with the fast axes oriented substantially perpendicular to each other. Each entry wave plate is oriented relative to a transmission axis of the input polarizer at a respective angle. An output polarizer is positioned to receive a signal output from the wave-plate structure and selectively transmits the signal based on the polarization state.

[Studies on development of pharmaceutical preparation with the purpose of improving controlled-release and bioavailability].

PubMed

Goto, S

1995-11-01

During the past fifteen years, the experiments based on three main propositions were proceeded to carry out in our laboratory, that is, (1) Microencapsulation: The method of solvent evaporation in water or oily phases was adopted because of its comparative simplicity in the procedure and its high reproducibility. The application of pharmacokinetic consideration to in vivo evaluation of microencapsulated drugs using beagle dogs intended for obtaining controlled-release by oral administration. The pullulan acetate phthalate microcapsules containing cefadroxil were prepared by the solvent evaporation method in liquid paraffin and showed a zero-order dissolution pattern in pH 6-7.4. (2) Rectal gel preparation: The hydrogels and xerogels were prepared by Eudispert hv. These gels have excellent staying properties in the lower part of the rectum, over a fairly long period. Eudispert hv hydrogels or xerogels containing propentfylline were tested for avoidance of the first-pass metabolism. The absolute bioavailability of propentofylline from gel preparations was almost 100%. (3) Binary vehicle for transdermal delivery: The effects of glycerides, short-chain alcohols and their binary vehicles as donor components on the skin permeation of ketoprofen across the excised hairless mouse skin were evaluated with the diffusion cell. Among single vehicles, Panasate 800 as lipophilic vehicle and ethanol as hydrophilic vehicle showed the effective permeation flux of ketoprofen. The greatest enhancement was observed in an ethanol/Panasate 800 (40/60) binary vehicle. The relationship between lipophilicity and skin permeability of 16 drugs from the ethanol/Panasate 800 (40/60) binary vehicle showed a parabolic shape with a peak at a more hydrophilic range compared with other past references.

Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

PubMed

Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

2013-11-01

The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non-conforming batches that are explicitly "out of specification" under real-time test conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

50 CFR 635.24 - Commercial retention limits for sharks, swordfish, and BAYS tunas.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Small Boat permit trip limit is set above zero. The current shark trip limit for HMS Commercial Caribbean Small Boat permit holders is set at zero. (5) A person who owns or operates a vessel that has been... released in the water in a manner that maximizes survival. (7) [Reserved] (8) Inseason trip limit...

The development of a peak-time criterion for designing controlled-release devices.

PubMed

Simon, Laurent; Ospina, Juan

2016-08-25

This work consists of estimating dynamic characteristics for topically-applied drugs when the magnitude of the flux increases to a maximum value, called peak flux, before declining to zero. This situation is typical of controlled-released systems with a finite donor or vehicle volume. Laplace transforms were applied to the governing equations and resulted in an expression for the flux in terms of the physical characteristics of the system. After approximating this function by a second-order model, three parameters of this reduced structure captured the essential features of the original process. Closed-form relationships were then developed for the peak flux and time-to-peak based on the empirical representation. Three case studies that involve mechanisms, such as diffusion, partitioning, dissolution and elimination, were selected to illustrate the procedure. The technique performed successfully as shown by the ability of the second-order flux to match the prediction of the original transport equations. A main advantage of the proposed method is that it does not require a solution of the original partial differential equations. Less accurate results were noted for longer lag times. Copyright © 2016 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.

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

PubMed Central

Mohammadi, Saman; Jones, Lyndon; Gorbet, Maud

2014-01-01

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes. PMID:25207851

Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

PubMed Central

Arora, Gurpreet; Malik, Karan; Singh, Inderbir; Arora, Sandeep; Rana, Vikas

2011-01-01

The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations. PMID:22171313

A new approach to pattern metrology

NASA Astrophysics Data System (ADS)

Ausschnitt, Christopher P.

2004-05-01

We describe an approach to pattern metrology that enables the simultaneous determination of critical dimensions, overlay and film thickness. A single optical system captures nonzero- and zero-order diffracted signals from illuminated grating targets, as well as unpatterned regions of the surrounding substrate. Differential targets provide in situ dimensional calibration. CD target signals are analyzed to determine average dimension, profile attributes, and effective dose and defocus. In turn, effective dose and defocus determines all CDs pre-correlated to the dose and focus settings of the exposure tool. Overlay target signals are analyzed to determine the relative reflectivity of the layer pair and the overlay error between them. Compared to commercially available pattern metrology (SEM, optical microscopy, AFM, scatterometry and schnitzlometry), our approach promises improved signal-to-noise, higher throughput and smaller targets. We have dubbed this optical chimera MOXIE (Metrology Of eXtremely Irrational Exuberance).

"Zeroing" in on mathematics in the monkey brain.

PubMed

Beran, Michael J

2016-03-01

A new study documented that monkeys showed selective neuronal responding to the concept of zero during a numerical task, and that there were two distinct classes of neurons that coded the absence of stimuli either through a discrete activation pattern (zero or not zero) or a continuous one for which zero was integrated with other numerosities in the relative rate of activity. These data indicate that monkeys, like humans, have a concept of zero that is part of their analog number line but that also may have unique properties compared to other numerosities.

Phase shifts in the Fourier spectra of phase gratings and phase grids: an application for one-shot phase-shifting interferometry.

PubMed

Toto-Arellano, Noel-Ivan; Rodriguez-Zurita, Gustavo; Meneses-Fabian, Cruz; Vazquez-Castillo, Jose F

2008-11-10

Among several techniques, phase shifting interferometry can be implemented with a grating used as a beam divider to attain several interference patterns around each diffraction order. Because each pattern has to show a different phase-shift, a suitable shifting technique must be employed. Phase gratings are attractive to perform the former task due to their higher diffraction efficiencies. But as is very well known, the Fourier coefficients of only-phase gratings are integer order Bessel functions of the first kind. The values of these real-valued functions oscillate around zero, so they can adopt negative values, thereby introducing phase shifts of pi at certain diffraction orders. Because this almost trivial fact seems to have been overlooked in the literature regarding its practical implications, in this communication such phase shifts are stressed in the description of interference patterns obtained with grating interferometers. These patterns are obtained by placing two windows in the object plane of a 4f system with a sinusoidal grating/grid in the Fourier plane. It is shown that the corresponding experimental observations of the fringe modulation, as well as the corresponding phase measurements, are all in agreement with the proposed description. A one-shot phase shifting interferometer is finally proposed taking into account these properties after proper incorporation of modulation of polarization.

Statistics of Atmospheric Circulations from Cumulant Expansions

NASA Astrophysics Data System (ADS)

Marston, B.; Sabou, F.

2010-12-01

Large-scale atmospheric flows are not so nonlinear as to preclude their direct statistical simulation (DSS) by systematic expansions in equal-time cumulants. Such DSS offers a number of advantages: (i) Low-order statistics are smoother in space and stiffer in time than the underlying instantaneous flows, hence statistically stationary or slowly varying fixed points can be described with fewer degrees of freedom and can also be accessed rapidly. (ii) Convergence with increasing resolution can be demonstrated. (iii) Finally and most importantly, DSS leads more directly to understanding, by integrating out fast modes, leaving only the slow modes that contain the most interesting information. This makes the approach ideal for simulating and understanding modes of the climate system, including changes in these modes that are driven by climate change. The equations of motion for the cumulants form an infinite hierarchy. The simplest closure is to set the third and higher order cumulants to zero. We extend previous work (Marston, Conover, and Schneider 2008) along these lines to two-layer models of the general circulation which has previously been argued to be only weakly nonlinear (O'Gorman and Schneider, 2006). Equal-time statistics so obtained agree reasonably well with those accumulated by direct numerical simulation (DNS) reproducing efficiently the midlatitude westerlies and storm tracks, tropical easterlies, and non-local teleconnection patterns (Marston 2010). Low-frequency modes of variability can also be captured. The primitive equation model of Held & Suarez, with and without latent heat release, is investigated, providing a test of whether DSS accurately reproduces the responses to simple climate forcings as found by DNS.

Arthroscopically assisted knee contracture release secondary to melorheostosis: a case report.

PubMed

Claramunt, Raúl Torres; López, Xavier Pelfort; Palou, Enric Cáceres; García, Joan C Monllau; Verdie, Lluís Puig

2011-02-01

Melorheostosis is a rare non-hereditary bone disease characterized by a radiographic pattern of flowing hyperostosis along the cortex with sclerotomal distribution. We report a case of a patient with severe knee contracture and a restricted range of motion caused by intraarticular bone fragment and hyperostotic bone lesions secondary to melorheostosis. An arthroscopically assisted approach was used successfully in order to remove free bone fragments and to release the hyperostotic lesions in the bone cortex of the distal femur.

Osmotic pellet system comprising osmotic core and in-process amorphized drug in polymer-surfactant layer for controlled delivery of poorly water-soluble drug.

PubMed

Saindane, Nilesh; Vavia, Pradeep

2012-09-01

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs. Copyright © 2012 Wiley Periodicals, Inc.

Electromagnetic scattering by a uniaxial anisotropic sphere located in an off-axis Bessel beam.

PubMed

Qu, Tan; Wu, Zhen-Sen; Shang, Qing-Chao; Li, Zheng-Jun; Bai, Lu

2013-08-01

Electromagnetic scattering of a zero-order Bessel beam by an anisotropic spherical particle in the off-axis configuration is investigated. Based on the spherical vector wave functions, the expansion expression of the zero-order Bessel beam is derived, and its convergence is numerically discussed in detail. Utilizing the tangential continuity of the electromagnetic fields, the expressions of scattering coefficients are given. The effects of the conical angle of the wave vector components of the zero-order Bessel beam, the ratio of the radius of the sphere to the central spot radius of the zero-order Bessel beam, the shift of the beam waist center position along both the x and y axes, the permittivity and permeability tensor elements, and the loss of the sphere on the radar cross section (RCS) are numerically analyzed. It is revealed that the maximum RCS appears in the conical direction or neighboring direction when the sphere is illuminated by a zero-order Bessel beam. Furthermore, the RCS will decrease and the symmetry is broken with the shift of the beam waist center.

Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine

PubMed Central

Chen, Yufei; Traore, Yannick Leandre; Li, Amanda; Fowke, Keith R; Ho, Emmanuel A

2014-01-01

Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections. PMID:25336923

Polyisoprene matrix for progesterone release: in vitro and in vivo studies.

PubMed

Heredia, V; Bianco, I D; Tríbulo, H; Tríbulo, R; Seoane, M Ferro; Faudone, S; Cuffini, S L; Demichelis, N A; Schalliol, H; Beltramo, D M

2009-12-01

Latex, a polyisoprene (PI) hydrophobic elastomer, was evaluated in vitro and in vivo as a matrix for intravaginal steroid hormone delivery. Matrices containing hormone were prepared by swelling latex in chloroform that contained soluble progesterone (P4). In vitro studies demonstrate that P4 release from PI follows a zero order model during at least 100 h and depends on initial load up to 10 mg cm(-2). The release of P4 from a PI matrix was found to be two times faster than from a polydimethylsiloxane (PDMS) matrix. FT-IR and X-ray powder diffraction analysis of P4 polymorphs show that when nucleated in PDMS, the hormone crystallizes only in alpha-form while in latex, crystallizes as a mixture of alpha- and beta-form. In vivo studies show that devices with a PI matrix containing 0.5 g of P4 are effective to reach plasma levels above 1 ng ml(-1) that are needed to synchronize estrous in cattle. Altogether, the results show that PI, a vulcanized polymer with a carbon-carbon backbone, can be used as a new matrix for the intravaginal administration of progesterone with improved release profile than silicone and that the matrix can influence the crystalline state of the hormone.

Mechanisms of floc destruction during anaerobic and aerobic digestion and the effect on conditioning and dewatering of biosolids.

PubMed

Novak, John T; Sadler, Mary E; Murthy, Sudhir N

2003-07-01

Laboratory anaerobic and aerobic digestion studies were conducted using waste activated sludges from two municipal wastewater treatment plants in order to gain insight into the mechanisms of floc destruction that account for changes in sludge conditioning and dewatering properties when sludges undergo anaerobic and aerobic digestion. Batch digestion studies were conducted at 20 degrees C and the dewatering properties, solution biopolymer concentration and conditioning dose requirements measured. The data indicated that release of biopolymer from sludges occurred under both anaerobic and aerobic conditions but that the release was much greater under anaerobic conditions. In particular, the release of protein into solution was 4-5 times higher under anaerobic than under aerobic conditions. Both the dewatering rate, as characterized by the specific resistance to filtration and the amount of polymer conditioning chemicals required was found to depend directly on the amount of biopolymer (protein + polysaccharide) in solution. Little difference in dewatering properties and conditioning doses was seen between the two activated sludges from different plants. Differences in the cations released between anaerobic and aerobic digestion suggest that the digestion mechanisms differ for the two types of processes. Enzyme activity data showed that during aerobic digestion, polysaccharide degradation activity decreased to near zero and this was consistent with the accumulation of polysaccharides in aerobic digesters.

Ex-vivoand in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base.

PubMed

Cavallari, Cristina; Brigidi, Patrizia; Fini, Adamo

2015-12-30

The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichia coli and Staphylococcus aureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system. Copyright © 2015. Published by Elsevier B.V.

Zero-order bows in radially inhomogeneous spheres: direct and inverse problems.

PubMed

Adam, John A

2011-10-01

Zero-order ray paths are examined in radially inhomogeneous spheres with differentiable refractive index profiles. It is demonstrated that zero-order and sometimes twin zero-order bows can exist when the gradient of refractive index is sufficiently negative. Abel inversion is used to "recover" the refractive index profiles; it is therefore possible in principle to specify the nature and type of bows and determine the refractive index profile that induces them. This may be of interest in the field of rainbow refractometry and optical fiber studies. This ray-theoretic analysis has direct similarities with the phenomenon of "orbiting" and other phenomena in scattering theory and also in seismological, surface gravity wave, and gravitational "lensing" studies. For completeness these topics are briefly discussed in the appendixes; they may also be of pedagogic interest.

Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.

PubMed

Gobburu, J V; Agersø, H; Jusko, W J; Ynddal, L

1999-09-01

To examine the pharmacokinetics (PK) and pharmacodynamics (PD) of ipamorelin, a growth hormone (GH) releasing peptide, in healthy volunteers. A trial was conducted with a dose escalation design comprising 5 different infusion rates (4.21, 14.02, 42.13, 84.27 and 140.45 nmol/kg over 15 minutes) with eight healthy male subjects at each dose level. Concentrations of ipamorelin and growth hormone were measured. The PK parameters showed dose-proportionality, with a short terminal half-life of 2 hours, a clearance of 0.078 L/h/kg and a volume of distribution at steady-state of 0.22 L/kg. The time course of GH stimulation by ipamorelin showed a single episode of GH release with a peak at 0.67 hours and an exponential decline to negligible GH concentration at all doses. The ipamorelin-GH concentration relationship was characterized using an indirect response model and population fitting. The model employed a zero-order GH release rate over a finite duration of time to describe the episodic release of GH. Ipamorelin induces the release of GH at all dose levels with the concentration (SC50) required for half-maximal GH stimulation of 214 nmol/L and a maximal GH production rate of 694 mIU/L/h. The inter-individual variability of the PD parameters was larger than that of the PK parameters. The proposed PK/PD model provides a useful characterization of ipamorelin disposition and GH responses across a range of doses.

Synthesis of amphiphilic alternating polyesters with oligo(ethylene glycol) side chains and potential use for sustained release drug delivery.

PubMed

Wang, Wei; Ding, Jianxun; Xiao, Chunsheng; Tang, Zhaohui; Li, Di; Chen, Jie; Zhuang, Xiuli; Chen, Xuesi

2011-07-11

Novel amphiphilic alternating polyesters, poly((N-phthaloyl-l-glutamic anhydride)-co-(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane) (P(PGA-co-ME(2)MO)), were synthesized by alternating copolymerization of PGA and ME(2)MO. The structures of the synthesized polyesters were characterized by (1)H NMR, (13)C NMR, FT-IR, and GPC analyses. Because of the presence of oligo(ethylene glycol) (OEG) side chains, the polyesters could self-assemble into thermosensitive micelles. Dynamic light scattering (DLS) showed that these micelles underwent thermoinduced size decrease without intermicellar aggregation. In vitro methyl thiazolyl tetrazolium (MTT) assay demonstrated that the polyesters were biocompatible to Henrietta Lacks (HeLa) cells, rendering their potential for drug delivery applications. Two hydrophobic drugs, rifampin and doxorubicin (DOX), were loaded into the polyester micelles and observed to be released in a zero-order sustained manner. The sustained release could be accelerated in lower pH or in the presence of proteinase K, due to the degradation of the polyester under these conditions. Remarkably, in vitro cell experiments showed that the polyester micelles accomplished fast release of DOX inside cells and higher anticancer efficacy as compared with the free DOX. With enhanced stability during circulation condition and accelerated drug release at the target sites (e.g., low pH or enzyme presence), these novel polyesters with amphiphilic structures are promising to be used in sustained release drug delivery systems.

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.

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test

PubMed Central

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-01-01

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

Synthesis and controlled release properties of 2,4-dichlorophenoxy acetate-zinc layered hydroxide nanohybrid

NASA Astrophysics Data System (ADS)

Bashi, Abbas M.; Hussein, Mohd Zobir; Zainal, Zulkarnain; Tichit, Didier

2013-07-01

Direct reaction of ZnO with 2,4-dichlorophenoxyacetic acid (24D) solutions of different concentrations allows obtaining new organic-inorganic nanohybrid materials formed by intercalation of 24D into interlayers of zinc layered hydroxide (ZLH). XRD patterns show a progressive evolution of the structure as 24D concentration increases. The nanohybrid obtained at higher 24D concentration (24D-ZLH(0.4)) reveals a well ordered layered structure with two different basal spacings at 25.2 Å and 24 Å. The FTIR spectrum showing the vibrations bands of the functional groups of 24D and of the ZLH confirms the intercalation. SEM images are in agreement with the structural evolution observed by XRD and reveal the ribbon morphology of the nanohybrids. The release studies of 24D showed a rapid release of 94% for the first 100 min governed by the pseudo-second order kinetic model.

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.

Validation of zero-order feedback strategies for medium range air-to-air interception in a horizontal plane

NASA Technical Reports Server (NTRS)

Shinar, J.

1982-01-01

A zero order feedback solution of a variable speed interception game between two aircraft in the horizontal plane, obtained by using the method of forced singular perturbation (FSP), is compared with the exact open loop solution. The comparison indicates that for initial distances of separation larger than eight turning radii of the evader, the accuracy of the feedback approximation is better than one percent. The result validates the zero order FSP approximation for medium range air combat analysis.

Root exudation of phytosiderophores from soil-grown wheat

PubMed Central

Oburger, Eva; Gruber, Barbara; Schindlegger, Yvonne; Schenkeveld, Walter D C; Hann, Stephan; Kraemer, Stephan M; Wenzel, Walter W; Puschenreiter, Markus

2014-01-01

For the first time, phytosiderophore (PS) release of wheat (Triticum aestivum cv Tamaro) grown on a calcareous soil was repeatedly and nondestructively sampled using rhizoboxes combined with a recently developed root exudate collecting tool. As in nutrient solution culture, we observed a distinct diurnal release rhythm; however, the measured PS efflux was c. 50 times lower than PS exudation from the same cultivar grown in zero iron (Fe)-hydroponic culture. Phytosiderophore rhizosphere soil solution concentrations and PS release of the Tamaro cultivar were soil-dependent, suggesting complex interactions of soil characteristics (salinity, trace metal availability) and the physiological status of the plant and the related regulation (amount and timing) of PS release. Our results demonstrate that carbon and energy investment into Fe acquisition under natural growth conditions is significantly smaller than previously derived from zero Fe-hydroponic studies. Based on experimental data, we calculated that during the investigated period (21–47 d after germination), PS release initially exceeded Fe plant uptake 10-fold, but significantly declined after c. 5 wk after germination. Phytosiderophore exudation observed under natural growth conditions is a prerequisite for a more accurate and realistic assessment of Fe mobilization processes in the rhizosphere using both experimental and modeling approaches. PMID:24890330

Continuous twin screw granulation of controlled release formulations with various HPMC grades.

PubMed

Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2016-09-25

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. Copyright © 2016 Elsevier B.V. All rights reserved.

Entropy and biological systems: experimentally-investigated entropy-driven stacking of plant photosynthetic membranes.

PubMed

Jia, Husen; Liggins, John R; Chow, Wah Soon

2014-02-24

According to the Second Law of Thermodynamics, an overall increase of entropy contributes to the driving force for any physicochemical process, but entropy has seldom been investigated in biological systems. Here, for the first time, we apply Isothermal Titration Calorimetry (ITC) to investigate the Mg(2+)-induced spontaneous stacking of photosynthetic membranes isolated from spinach leaves. After subtracting a large endothermic interaction of MgCl₂ with membranes, unrelated to stacking, we demonstrate that the enthalpy change (heat change at constant pressure) is zero or marginally positive or negative. This first direct experimental evidence strongly suggests that an entropy increase significantly drives membrane stacking in this ordered biological structure. Possible mechanisms for the entropy increase include: (i) the attraction between discrete oppositely-charged areas, releasing counterions; (ii) the release of loosely-bound water molecules from the inter-membrane gap; (iii) the increased orientational freedom of previously-aligned water dipoles; and (iv) the lateral rearrangement of membrane components.

Entropy and biological systems: Experimentally-investigated entropy-driven stacking of plant photosynthetic membranes

PubMed Central

Jia, Husen; Liggins, John R.; Chow, Wah Soon

2014-01-01

According to the Second Law of Thermodynamics, an overall increase of entropy contributes to the driving force for any physicochemical process, but entropy has seldom been investigated in biological systems. Here, for the first time, we apply Isothermal Titration Calorimetry (ITC) to investigate the Mg2+-induced spontaneous stacking of photosynthetic membranes isolated from spinach leaves. After subtracting a large endothermic interaction of MgCl2 with membranes, unrelated to stacking, we demonstrate that the enthalpy change (heat change at constant pressure) is zero or marginally positive or negative. This first direct experimental evidence strongly suggests that an entropy increase significantly drives membrane stacking in this ordered biological structure. Possible mechanisms for the entropy increase include: (i) the attraction between discrete oppositely-charged areas, releasing counterions; (ii) the release of loosely-bound water molecules from the inter-membrane gap; (iii) the increased orientational freedom of previously-aligned water dipoles; and (iv) the lateral rearrangement of membrane components. PMID:24561561

Kepler Commissioning Data for Measurement of the Pixel Response Function and Focal Plane Geometry

NASA Technical Reports Server (NTRS)

Bryson, Stephen T.

2017-01-01

This document describes the Kepler PRF/FPG data release. This data was taken on April 27-29, 2009, during Kepler's commissioning phase in order to measure the pixel response function (PRF) (Bryson et al., 2010a) and focal plane geometry (FPG) (Tenenbaum and Jenkins, 2010). 33,424 stellar targets were observed for 243 long cadences, each with a duration of 14.7 minutes (half the duration of a normal Kepler long cadence). During these 243 cadences the Kepler photometer was moved, pointing in a dither pattern to facilitate PRF measurement. Motion occurred during the even cadences (second, fourth, etc.), with the telescope in stable fine point at each pointing in the dither pattern during the odd cadences (first, third, etc.). The first and last cadences were at the center of the dither pattern. Motion cadences are included in this release, but they do not contain any data. For details on how this data was used to derive the Kepler PRF and FPG models, see Bryson et al. (2010a) and Tenenbaum and Jenkins (2010). Descriptions of the PRF and FPG models are found in Thompson et al. (2016), x2.3.5.17 and x2.3.5.16 respectively. The data in this release can be used to recompute the Kepler PRF and FPG. Such a reconstruction, however, would not reflect measured seasonal changes in the PRF described in Van Cleve et al. (2016b), x5.2.The dither pattern is shown in Figure 1. The crosses show the commanded pointings and the circles show the measured pointings. Measured pointings are different from the commanded pointings due to the early state of calibration of the fine guidance sensors during commissioning (Van Cleve et al., 2016a). The measured offsets from the center of the pattern are given in RADEC offsets and pixel offsets in Table 1. The order of the offsets was randomized during data collection to avoid time-dependent systematics.

Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

PubMed Central

Yarce, Cristhian J.; Echeverri, Juan D.; Palacio, Mario A.; Rivera, Carlos A.; Salamanca, Constain H.

2017-01-01

This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate), besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isobutylene-alt-maleic acid) (hydrophilic), sodium salt of poly(maleic acid-alt-octadecene) (amphiphilic), poly(maleic anhydride-alt-octadecene) (hydrophobic) and the reference polymer hydroxyl-propyl-methyl-cellulose (HPMC). Each material alone and in blends underwent spectroscopic characterization by FTIR, thermal characterization by DSC and granulometric characterization using flow and compaction tests. Each tablet was prepared at different polymer ratios of 0%, 10%, 20%, 30% and 40%, and the surface properties were determined, including the roughness by micro-visualization, contact angle and water absorption rate by the sessile drop method and obtaining Wadh and surface free energy (SFE) using the semi-empirical models of Young–Dupré and  Owens-Wendt-Rabel-Käelbe (OWRK), respectively. Dissolution profiles were determined simulating physiological conditions in vitro, where the kinetic models of order-zero, order-one, Higuchi and Korsmeyer–Peppas were evaluated. The results showed a strong relationship between the proportion and nature of the polymer to the surface thermodynamic properties and kinetic release mechanism. PMID:28125020

Design, Development, and Optimization of Dexibuprofen Microemulsion Based Transdermal Reservoir Patches for Controlled Drug Delivery

PubMed Central

Ali, Fatima Ramzan; Yousuf, Rabia Ismail; Ali, Syed Abid; Imtiaz, Muhammad Suleman; Bashir, Lubna; Naz, Shazia

2017-01-01

The aim of the study was to develop a reservoir-type transdermal patch for a controlled delivery of dexibuprofen and to evaluate its in vivo anti-inflammatory activity in Albino Wistar rats. In order to develop these patches, six formulations of dexibuprofen microemulsion comprising ethyl oleate, Tween 80: PG (2 : 1), and water were prepared by simplex lattice design and characterized. The reservoir compartment was filled with these microemulsions and in vitro release and skin permeation were assessed. The optimized patch was obtained on the basis of the responses: Q24 and flux. The impact of drug loading, surface area, membrane thickness, adhesive, and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction and in vivo anti-inflammatory activity of optimized patch were evaluated. Stability study at three different temperatures for three months was carried out. The result suggests that a membrane based patch with zero-order release rate, Q24 of 79.13 ± 3.08%, and maximum flux of 331.17 µg/cm2h can be obtained exhibiting suitable anti-inflammatory activity with no visible skin sensitivity reaction. The outcomes of stability study recommend storage of patches at 4°C having shelf-life of 6.14 months. The study demonstrates that the reservoir-type transdermal patch of dexibuprofen microemulsion has a potential of delivering drug across skin in controlled manner with required anti-inflammatory activity. PMID:29090219

Creation of vector beams from a polarization diffraction grating using a programmable liquid crystal spatial light modulator and a q-plate

NASA Astrophysics Data System (ADS)

Badham, Katherine Emily

This thesis presents the ability of complete polarization control of light to create a polarization diffraction grating (PDG). This system has the ability to create diffracted light with each order having a separate high-order polarization state in one location on the optical axis. First, an external Excel program is used to create a grating phase profile from userspecified target diffraction orders. High-order vector beams in this PDG are created using a combination of two devices---a liquid crystal spatial light modulator (LC-SLM) manufactured by Seiko Epson, and a tunable q -plate from Citizen Holdings Co. The transmissive SLM is positioned in an optical setup with a reflective architecture allowing control over both the horizontal and vertical components of the laser beam. The SLM has its LC director oriented vertically only affecting the vertically polarized state, however, the optical setup allows modulation of both vertical and horizontal components by the use of a quarter-wave plate (QWP) and a mirror to rotate the polarizations 90 degrees. Each half of the SLM is encoded with an anisotropic phase-only diffraction grating which are superimposed to create a select number of orders with the desired polarization states and equally distributed intensity. The technique of polarimetry is used to confirm the polarization state of each diffraction order. The q-plate is an inhomogeneous birefringent waveplate which has the ability to convert zero-order vector beams into first-order vector beams. The physical placement of this device into the system converts the orders with zero-order polarization states to first-order polarization states. The light vector patterns of each diffraction order confirm which first-order polarization state of is produced. A specially made PDG sextuplicator is encoded onto the SLM to generate six diffraction orders with separate states of polarization.

A comparison of zero-order, first-order, and monod biotransformation models

USGS Publications Warehouse

Bekins, B.A.; Warren, E.; Godsy, E.M.

1998-01-01

Under some conditions, a first-order kinetic model is a poor representation of biodegradation in contaminated aquifers. Although it is well known that the assumption of first-order kinetics is valid only when substrate concentration, S, is much less than the half-saturation constant, K(s), this assumption is often made without verification of this condition. We present a formal error analysis showing that the relative error in the first-order approximation is S/K(S) and in the zero-order approximation the error is K(s)/S. We then examine the problems that arise when the first-order approximation is used outside the range for which it is valid. A series of numerical simulations comparing results of first- and zero-order rate approximations to Monod kinetics for a real data set illustrates that if concentrations observed in the field are higher than K(s), it may better to model degradation using a zero-order rate expression. Compared with Monod kinetics, extrapolation of a first-order rate to lower concentrations under-predicts the biotransformation potential, while extrapolation to higher concentrations may grossly over-predict the transformation rate. A summary of solubilities and Monod parameters for aerobic benzene, toluene, and xylene (BTX) degradation shows that the a priori assumption of first-order degradation kinetics at sites contaminated with these compounds is not valid. In particular, out of six published values of KS for toluene, only one is greater than 2 mg/L, indicating that when toluene is present in concentrations greater than about a part per million, the assumption of first-order kinetics may be invalid. Finally, we apply an existing analytical solution for steady-state one-dimensional advective transport with Monod degradation kinetics to a field data set.A formal error analysis is presented showing that the relative error in the first-order approximation is S/KS and in the zero-order approximation the error is KS/S where S is the substrate concentration and KS is the half-saturation constant. The problems that arise when the first-order approximation is used outside the range for which it is valid are examined. A series of numerical simulations comparing results of first- and zero-order rate approximations to Monod kinetics for a real data set illustrates that if concentrations observed in the field are higher than KS, it may be better to model degradation using a zero-order rate expression.

Characterizing Featureless Mott Insulating State by Quasiparticle Interferences - A DMFT Prospect

NASA Astrophysics Data System (ADS)

Mukherjee, Shantanu; Lee, Wei-Cheng

In this talk we discuss the quasiparticle interferences (QPIs) of a Mott insulator using a T-matrix formalism implemented with the dynamical mean-field theory (T-DMFT). In the Mott insulating state, the DMFT predicts a singularity in the real part of electron self energy s (w) at low frequencies, which completely washes out the QPI at small bias voltage. However, the QPI patterns produced by the non-interacting Fermi surfaces can appear at a critical bias voltage in Mott insulating state. The existence of this non-zero critical bias voltage is a direct consequence of the singular behavior of Re[s (w)] /sim n/w with n behaving as the 'order parameter' of Mott insulating state. We propose that this reentry of non-interacting QPI patterns could serve as an experimental signature of Mott insulating state, and the 'order parameter' can be experimentally measured W.C.L acknowledges financial support from start up fund from Binghamton University.

The elimination of zero-order diffraction of 10.6 μm infrared digital holography

NASA Astrophysics Data System (ADS)

Liu, Ning; Yang, Chao

2017-05-01

A new method of eliminating the zero-order diffraction in infrared digital holography has been raised in this paper. Usually in the reconstruction of digital holography, the spatial frequency of the infrared thermal imager, such as microbolometer, cannot be compared to the common visible CCD or CMOS devices. The infrared imager suffers the problems of large pixel size and low spatial resolution, which cause the zero-order diffraction a severe influence of the reconstruction process of digital holograms. The zero-order diffraction has very large energy and occupies the central region in the spectrum domain. In this paper, we design a new filtering strategy to overcome this problem. This filtering strategy contains two kinds of filtering process which are the Gaussian low-frequency filter and the high-pass phase averaging filter. With the correct set of the calculating parameters, these filtering strategies can work effectively on the holograms and fully eliminate the zero-order diffraction, as well as the two crossover bars shown in the spectrum domain. Detailed explanation and discussion about the new method have been proposed in this paper, and the experiment results are also demonstrated to prove the performance of this method.

Development of sustained and dual drug release co-extrusion formulations for individual dosing.

PubMed

Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

2015-01-01

In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

PubMed

Vemula, Sateesh Kumar

2015-12-01

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

PubMed

Rehman, Fozia; Rahim, Abdur; Airoldi, Claudio; Volpe, Pedro L O

2016-02-01

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system. Copyright © 2015 Elsevier B.V. All rights reserved.

Bifunctional capsular dosage form: novel fanicular cylindrical gastroretentive system of clarithromycin and immediate release granules of ranitidine HCl for simultaneous delivery.

PubMed

Rajput, Pallavi; Singh, Deshvir; Pathak, Kamla

2014-01-30

The study was aimed to develop a bifunctional single unit capsular system containing gastroretentive funicular cylindrical system (FCS) for controlled local delivery of clarithromycin and immediate release of ranitidine HCl. A 2(3) full factorial design was used to prepare gastroretentive FCS of clarithromycin using polyacrylamide (PAM), HPMC E15LV and Carbopol 934 P. The FCSs were evaluated for % cumulative drug release, floating time and in vitro detachment stress. Among the eight formulations, FCS5 (containing PAM and Carbopol 934 P at high and HPMC E15LV at low levels) showed % cumulative drug release of 97.09±1.14% in 8 h, floating time of 3 h and detachment stress of 8303.64±0.34 dynes/cm(2). Evaluation of optimized FCS by novel dynamic in vitro test proved superior bioadhesivity than cylindrical system under aggressive simulated peristaltic activity. Magnetic resonance imaging elucidated zero order release via constant swelling and erosion of FCS5. In vitro permeability across gastric mucin ensured its potential for effective eradication of deep seated Helicobactor pylori in gastric linings. The optimized FCS was combined with immediate release granules of rantidine HCl to get a bifunctional capsular dosage form. In vitro simultaneous drug release of clarithromycin and rantidine estimated by Vierordt's method exhibited a controlled drug release of 97.72±0.4% in 8 h for clarithromycin through FCS5 and 98.8±1.2% in 60 min from IR granules of ranitidine HCl. The novel system thus established its capability of simultaneous variable delivery of acid suppression agent and macrolide antibiotic that can be advantageous in clinical setting. Copyright © 2013 Elsevier B.V. All rights reserved.

Observations of mass fractionation of noble gases in synthetic methane hydrate

USGS Publications Warehouse

Hunt, Andrew G.; Pohlman, John; Stern, Laura A.; Ruppel, Carolyn D.; Moscati, Richard J.; Landis, Gary P.; Pinkston, John C.

2011-01-01

As a consequence of contemporary or longer term (since 15 ka) climate warming, gas hydrates in some settings are presently dissociating and releasing methane and other gases to the oceanatmosphere system. A key challenge in assessing the susceptibility of gas hydrates to warming climate is the lack of a technique able to distinguish between methane recently released from gas hydrates and methane emitted from leaky thermogenic reservoirs, shallow sublake and subseafloor sediments, coalbeds, and other sources. Carbon and deuterium stable isotopic data provide only a first-order characterization of methane sources, while gas hydrate can sequester any type of methane. Here, we investigate the possibility of exploiting the pattern of noble gas fractionation within the gas hydrate lattice to fingerprint methane released from gas hydrates. Starting with synthetic gas hydrate formed under careful laboratory conditions, we document complex noble gas fractionation patterns in the gases liberated during dissociation and explore the effects of aging and storage (e.g., in liquid nitrogen), as well as sampling and preservation procedures. The laboratory results confirm a unique noble gas fractionation pattern for gas hydrates, one that shows promise in evaluating modern natural gas seeps for a signature associated with gas hydrate dissociation.

Bullying and Zero-Tolerance Policies: The School to Prison Pipeline

ERIC Educational Resources Information Center

Berlowitz, Marvin J.; Frye, Rinda; Jette, Kelli M.

2017-01-01

The centrality of zero-tolerance policies as a component of anti-bullying strategies is the focus of this paper. A review of the literature of social justice advocates, journalists, and scholars reveals that zero-tolerance policies tend to push students out of public schools into the criminal justice system in a pattern of institutional racism.…

A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation.

PubMed

Li, Shujuan; Wang, Xiaoyu; Wang, Yingying; Zhao, Qianqian; Zhang, Lina; Yang, Xinggang; Liu, Dandan; Pan, Weisan

2015-01-01

In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na2CO3 at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12 h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.

No snow for Christmas: the impact of the 2015 extreme winter on CO2 fluxes in European mountain grasslands

NASA Astrophysics Data System (ADS)

Cremonese, Edoardo; Galvagno, Marta; Hammerle, Albin; Filippa, Gianluca; Wohlfahrt, Georg

2016-04-01

The increasing frequency in extreme climate events is very likely to impact the Alps since this region is characterized by very sensitive ecosystems. Typical alpine ecosystems such as mountain grasslands, show a strong seasonality in carbon uptake and release mostly driven by the onset and the end of the snow season. Extreme climate events, such as long warm and/or dry periods, could change typical snow cover temporal pattern, thereby altering the duration of the period of CO2 uptake and release. In recent years many studies have analyzed the impact of delayed or anticipated snowmelt on alpine plant phenology, growth and carbon cycling. However, little is known on the effects of a delayed onset of the snow season. During 2015 the whole planet witnessed several record-breaking warm spells which exceptionally warmed the Alps where the temperature anomaly reached +4°C during both the autumn and winter periods. In particular, the onset of the 2015 winter in the Alps was marked by one of the most prolonged lack of snow in years. In this study, we investigate and discuss the impact of the altered temperature and precipitation pattern during the autumn/winter 2015 on the net ecosystem CO2 exchange of mountain grasslands at high and low altitudes measured by means of the eddy covariance method. In particular we test the following hypotheses: (i) The presence of a snowpack impedes plant photosynthesis, while without a snowpack, plant net CO2 uptake may be possible even during wintertime provided temperatures are warm enough. (ii) Below a snowpack, soil temperatures are around zero degrees Celsius, allowing for microbial activity resulting in intermediate soil respiration; without a snow cover soil temperatures may be either lower or higher than zero degrees Celsius, decreasing or increasing soil respiration. The magnitude and direction of the net ecosystem CO2 exchange of mountain grassland ecosystems is governed by the complex interplay of the factors addressed in hypothesis (i) and (ii).

Rheological properties of PLGA film-based implants: correlation with polymer degradation and SPf66 antimalaric synthetic peptide release.

PubMed

Santoveña, A; Alvarez-Lorenzo, C; Concheiro, A; Llabrés, M; Fariña, J B

2004-02-01

This paper reports on the rheological properties of poly(D,L-lactic-co-glycolic acid) polymers (PLGA) dispersions used to form films and of the implants prepared by compression of SPf66 antimalaric peptide between several films, before application and during drug release. 25% PLGA (M(w)=48,000Da) dispersions in dichloromethane showed viscous Newtonian behaviour, being easy flowing and adaptable to the moulds. Evolution of viscoelastic properties, polymer molecular weight, and SPf66 release pattern from the implants immersed in various media was evaluated. Oscillatory shear test showed that freshly prepared implants have an elastic modulus, G', greater than the viscous modulus, G", being both practically independent of angular frequency. After 6 weeks immersion in a pH 7.4 phosphate buffer, G' and G" increased in almost one order of magnitude, despite of a significant polymer degradation. Polymer molecular weight decreased slowly during the first 10 days of immersion (a similar pattern was obtained at pHs 2 and 7.4) and then the degradation process accelerated (degradation index on day 7 equals to 0.89, and on day 14 equals to 16.5). SPf66 release profile followed a pattern similar to that of the polymer degradation index. These observations are explained in terms of changes in polymer structure and conformation that happen in the implant.

Modeling willingness to pay for land conservation easements: treatment of zero and protest bids and application and policy implications

Treesearch

Seong-Hoon Cho; Steven T. Yen; J. Michael Bowker; David H. Newman

2008-01-01

This study compares an ordered probit model and a Tobit model with selection to take into account both true zero and protest zero bids while estimating the willingness to pay (WTP) for conservation easements in Macon County, NC. By comparing the two models, the ordered/Unordered selection issue of the protest responses is analyzed to demonstrate how the treatment of...

Corrections Education and Employment Assistance "Down Under": Current and Emerging Practices and Paradigms

ERIC Educational Resources Information Center

Graffam, Joe; Shinkfield, Alison J.; Lavelle, Barbara

2014-01-01

This article provides a view of contemporary Australia in terms of patterns of offending and incarceration, the characteristics of its correctional systems, vocational education and training (VET) within correctional settings, and post-release employment of prisoners and offenders serving community-based orders (CBOs). A two-year case study of…

MEAN FLOW AND TURBULENCE MEASUREMENTS AROUND A 2-D ARRAY OF BUILDINGS IN A WIND TUNNEL

EPA Science Inventory

In order to predict the dispersion of harmful materials released in or near an urban environment, it is important to first understand the complex flow patterns which result from the interaction of the wind with buildings and, more commonly, clusters of buildings. Recent advanc...

Periodicity of sex pheromone biosynthesis, release and degradation in the lightbrown apple moth, Epiphyas postvittana (Walker).

PubMed

Foster, S P

2000-03-01

Pheromone titer in moths is a product of three processes occurring in or at the surface of the pheromone gland: biosynthesis, release, and intraglandular degradation, of pheromone. Changes in titers of sex pheromone, the fatty acyl pheromone analog (FAPA), and tetradecanoate, a pheromone biosynthetic intermediate, were studied in detail in the lightbrown apple moth, Epiphyas postvittana (Walker). Although changes in the pheromone titers in a day were relatively small, with the peak titer being 2-3 times greater than that at the trough, pheromone titer did show a distinct diel periodicity. Titer of the FAPA showed a similar, but less variable, diel pattern, but tetradecanoate titer showed little or no diel pattern. The pattern of pheromone titer suggested that females biosynthesize pheromone at two different rates during the photoperiod: a high rate during the latter half of the photophase and most of the scotophase, which is associated with a high pheromone titer, and a low rate throughout the first half of the photophase, which is associated with a low titer. Consistent with data on commencement of copulation, pheromone was released from the second hour of the scotophase through to the eighth hour. Pheromone release rate during this period appeared to be similar to the rate of pheromone biosynthesis. In contrast to the other two processes, pheromone degradation did not appear to have a diel pattern. Females decapitated at different times of the photoperiod showed a similar decline in pheromone titer, consistent with the reaction kinetics being first order in pheromone titer.

Design, formulation and evaluation of green tea chewing gum

PubMed Central

Aslani, Abolfazl; Ghannadi, Alireza; Khalafi, Zeinab

2014-01-01

Background: The main purpose of this study is to design, formulate and evaluate the green tea gums with a suitable taste and quality in order to produce an anti-oxidant chewing gum. Materials and Methods: Fresh green tea leaves obtained from Northern Iran for extraction. Maceration is the extraction method that is used in this study. The contents of caffeine, catechin and flavonoids of the hydro alcoholic extract were measured. Various formulations of the 120 mg green tea extract chewing gums with different sweeteners, flavoring agents and various gum bases were prepared afterward release pattern, content uniformity, organoleptic results and other properties were characterized. Results: The contents of caffeine, catechin and flavonoid of the hydro alcoholic extraction were 207.32 mg/g, 130.00 mg/g and 200.82 mg/g, respectively. Release pattern of green tea chewing gum with different gum base ratios and various sweeteners in phosphate buffer were prepared. A total of 60 persons who were 20-30 years of age, participated in our panel test for organoleptic properties such as taste, stiffness, stickiness, etc., Acceptable gum was the one with the same ratio of the used rubber bases. Cinnamon selected as the preferred taste by volunteers. Combination of aspartame, sugar and maltitol has appropriate taste. The effect of various sweetener on release pattern was negligible, on the other hand rubber bases ratio variation, changed the release pattern obviously. Conclusion: The green tea chewing gum with sugar, maltitol and aspartame sweeteners and cinnamon flavor, using the same rubber bases ratio may be a desirable antioxidant product. PMID:25161989

Osmotic pressure driven protein release from viscous liquid, hydrophobic polymers based on 5-ethylene ketal ε-caprolactone: potential and mechanism.

PubMed

Babasola, Iyabo Oladunni; Zhang, Wei; Amsden, Brian G

2013-11-01

In this study, the potential of low molecular weight, viscous liquid polymers based on 5-ethylene ketal ε-caprolactone for localized delivery of proteins via an osmotic pressure release mechanism was investigated. Furthermore, the osmotic release mechanism from viscous liquid polymers was elucidated. 5-Ethylene ketal ε-caprolactone was homopolymerized or copolymerized with D,L-lactide (DLLA) by ring-opening polymerization. Polymer hydrophobicity was adjusted by choice of initiator; hydrophobic polymers were prepared by initiating with octan-1-ol, while more hydrophilic polymers were prepared by initiating with 350 g/mol methoxy poly(ethylene glycol) (PEG). Particles consisting of bovine serum albumin (BSA) as a model protein drug were co-lyophilized with trehalose at 50:50 and 10:90 (w/w) ratios and were mixed into the polymers at 1% and/or 5% (w/w) particle loading. The release and mechanism of release of BSA from the polymers were assessed in vitro. BSA was released in a sustained manner, with a near zero-order release profile and with minimal burst effect for 5-80 days depending on the polymer's hydrophilicity; the release was faster from the PEG initiated polymers than from the octan-1-ol initiated polymers. Increasing the particle loading from 1% to 5% (w/w) resulted in a more noticeable burst effect, but did not significantly increase the mass fraction release rate. This release behavior was determined to proceed as follows. Release from the polymer was triggered by the water activity gradient between the surrounding aqueous medium and the saturated solution, which forms when water is absorbed from the surrounding medium to dissolve a given particle. The generated pressure initiates swelling around the particle/polymer interface and creates a superhydrated polymer region through which the solute is transported by convection, at a rate determined by the osmotic pressure generated. Copyright © 2013 Elsevier B.V. All rights reserved.

Release kinetics and cell viability of ibuprofen nanocrystals produced by melt-emulsification.

PubMed

Fernandes, A R; Dias-Ferreira, J; Cabral, C; Garcia, M L; Souto, E B

2018-06-01

The clinical use of poorly water-soluble drugs has become a big challenge in pharmaceutical development due to the compromised bioavailability of the drugs in vivo. Nanocrystals have been proposed as a formulation strategy to improve the dissolution properties of these drugs. The benefits of using nanocrystals in drug delivery, when compared to other nanoparticles, are related to their production facilities, simple structure, and suitability for a variety of administration routes. High pressure homogenization (HPH) is the most promising production process, which can be employed at low or high temperatures. Ibuprofen nanocrystals with a mean size below 175 nm, and polydispersity below 0.18, have been produced by melt-emulsification, followed by HPH. Two nanocrystal formulations, differing on the surfactant composition, have been produced, their in vitro ibuprofen release tested in Franz diffusion cells and adjusted to several kinetic models (zero order, first order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Baker-Lonsdale and Weibull model). Cell viability was assessed at 3, 6 and 24 h of incubation on human epithelial colorectal cells (Caco-2) by AlamarBlue ® colorimetric assay. For both formulations, Caco-2 cells viability was dependent on the drug concentration and time of exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Fibrous dosage forms by wet 3D-micro-patterning: process design, manufacture, and drug release rate.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-06-19

Recently, we have introduced fibrous dosage forms prepared by 3D-micro-patterning of drug-laden viscous melts. Such dosage forms enable predictable microstructures and increased drug release rates, and they can be manufactured continuously. However, melt processing is not applicable if the melting temperature of the formulation is greater than the degradation temperature of the drug or of the excipient. In this work, therefore, a continuous wet micro-patterning process that operates at ambient temperature is presented. The excipient is plasticized by a solvent and the patterned dosage form is solidified by air drying. Process models show that the micro-patterning time is the ratio of the fiber length in the dosage form and the velocity of the fiber stream. It was 1.3 minutes in the experiments, but can be reduced further. The drying time is limited by the diffusive flux of solvent through the fibers: it was about 3 minutes for the experimental conditions. Furthermore, models are developed to illustrate the effects of fiber radius, inter-fiber spacing, viscosity of the drug-excipient-solvent mixture, and drying conditions on the microstructure of the dosage form. Models and experimental results show that for a viscosity of the wet fibers of the order 10 3 Pa·s, both the patterned microstructure is well preserved and the crossed fibers are well bonded. Finally, the drug release rate by the dosage forms is experimentally determined and theoretically modeled. The results of the experiments validate the models fairly. Copyright © 2018. Published by Elsevier B.V.

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

PubMed

Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

2012-01-01

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

PubMed

Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

2001-01-05

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

Multi-layer polymeric implants for sustained release of chemopreventives

PubMed Central

Aqil, Farrukh; Jeyabalan, Jeyaprakash; Kausar, Hina; Bansal, Shyam S.; Sharma, Ram J.; Singh, Inder P.; Vadhanam, Manicka V.; Gupta, Ramesh C.

2012-01-01

Poor oral bioavailability limits the use of many chemopreventives in the prevention and treatment of cancer. To overcome this limitation, we report an improvised implant formulation (“coated” implants) using curcumin, individual curcuminoids, withaferin A and oltipraz. This method involves the coating of blank polycaprolactone implants with 20–30 layers of 10–20% polycaprolactone solution in dichloromethane containing 0.5–2% of the test agent. The in vitro release showed that while oltipraz was released with almost zero-order kinetics over eight weeks, curcumin, individual curcuminoids and withaferin A were released with some initial burst. The in vivo release was determined by grafting implants subcutaneously in A/J mice. When delivered by coated implants, oltipraz significantly diminished lung DNA adducts in mice treated with dibenzo[a, l]pyrene compared with sham treatment (28±7 versus 54±17 adducts/109 nucleotides). Withaferin A also diminished DNA adducts, but it was insignificant. Curcumin and individual curcuminoids were ineffective. Analysis of lung, liver and brain by UPLC-fluorescence showed the presence of the three test curcuminoids indicating effectiveness of the implant delivery system. Further, based on its known antitumor activity in vivo, withaferin A given via the implants significantly inhibited human lung cancer A549 xenograft in athymic nude mice, while it was ineffective when the same total dose was administered i.p. and required over 2-fold higher dose to elicit effectiveness. Together, our data suggest that coated polymeric implants can accommodate heat-labile compounds, can furnish sustained release for long duration, and elicit DNA damage-inhibiting and anti-tumor activities. PMID:22820161

A biodegradable device for the controlled release of Piper nigrum (Piperaceae) standardized extract to control Aedes aegypti (Diptera, Culicidae) larvae.

PubMed

Custódio, Kauê Muller; Oliveira, Joice Guilherme de; Moterle, Diego; Zepon, Karine Modolon; Prophiro, Josiane Somariva; Kanis, Luiz Alberto

2016-01-01

The significant increase in dengue, Zika, and chikungunya and the resistance of the Aedes aegypti mosquito to major insecticides emphasize the importance of studying alternatives to control this vector. The aim of this study was to develop a controlled-release device containing Piper nigrum extract and to study its larvicidal activity against Aedes aegypti. Piper nigrum extract was produced by maceration, standardized in piperine, and incorporated into cotton threads, which were inserted into hydrogel cylinders manufactured by the extrusion of carrageenan and carob. The piperine content of the extract and thread reservoirs was quantified by chromatography. The release profile from the device was assessed in aqueous medium and the larvicidal and residual activities of the standardized extract as well as of the controlled-release device were examined in Aedes aegypti larvae. The standardized extract contained 580mg/g of piperine and an LC50 value of 5.35ppm (24h) and the 3 cm thread reservoirs contained 13.83 ± 1.81mg of piperine. The device showed zero-order release of piperine for 16 days. The P. nigrum extract (25ppm) showed maximum residual larvicidal activity for 10 days, decreasing progressively thereafter. The device had a residual larvicidal activity for up to 37 days. The device provided controlled release of Piper nigrum extract with residual activity for 37 days. The device is easy to manufacture and may represent an effective alternative for the control of Aedes aegypti larvae in small water containers.

Risperidone mucoadhesive buccal tablets: formulation design, optimization and evaluation

PubMed Central

Çelik, Burak

2017-01-01

The aim of this study was to design and optimize risperidone (RIS) mucoadhesive buccal tablets for systemic delivery as an alternative route. Direct compression method was used for the preparation of buccal tablets, and screening studies were conducted with different polymers to determine their effects on tablet characteristics. Carbopol® (CP) and sodium alginate (SA) were selected as two polymer types for further optimization studies by applying response surface methodology. Tablet hardness (TH), ex vivo residence time (RT), and peak detachment force (DF) from buccal mucosa were selected as three important responses. Physicochemical compatibility of formulation excipients and RIS was evaluated by using Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analysis. In vitro drug release profiles and release kinetics were investigated; swelling index and matrix erosion studies were conducted. Optimum formulation consisted of 16.4% CP and 20.3% SA, which provided 7.67±0.29 hour ex vivo RT, 45.52±4.85 N TH, and 2.12±0.17 N DF. FT-IR spectroscopy and DSC analysis revealed that there was no chemical interaction present between tablet ingredients. Cumulative RIS release of >90% was achieved after 8 hours of in vitro dissolution studies, which was supported by swelling and matrix erosion analysis. Mechanism of RIS release was fitted best to zero-order model, while release exponent (n) value of 0.77 demonstrated an anomalous (non-Fickian) release, indicating combined erosion and swelling mechanism. The results suggested that optimized buccal tablets of RIS would be a promising and alternative delivery system for the treatment of schizophrenia. PMID:29225461

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design.

PubMed

Chauhan, Manvendra S; Kumar, Anil; Pathak, Kamla

2012-12-01

A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH 2.5 (low fed), pH 4.5 (intermediate fed), and pH 6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12 h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.

A novel solid dosage form of rifampicin and isoniazid with improved functionality.

PubMed

Gohel, Mukesh C; Sarvaiya, Krishnakant G

2007-08-24

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

Pore Water Transport of Enterococci out of Beach Sediments

PubMed Central

Phillips, Matthew C.; Solo-Gabriele, Helena M.; Reniers, Adrianus J. H. M.; Wang, John D.; Kiger, Russell T.; Abdel-Mottaleb, Noha

2011-01-01

Enterococci are used to evaluate the safety of beach waters and studies have identified beach sands as a source of these bacteria. In order to study and quantify the release of microbes from beach sediments, flow column systems were built to evaluate flow of pore water out of beach sediments. Results show a peak in enterococci (average of 10% of the total microbes in core) released from the sand core within one pore water volume followed by a marked decline to below detection. These results indicate that few enterococci are easily removed and that factors other than simple pore water flow control the release of the majority of enterococci within beach sediments. A significantly larger quantity and release of enterococci were observed in cores collected after a significant rain event suggesting the influx of fresh water can alter the release pattern as compared to cores with no antecedent rainfall. PMID:21945015

First-principles theory of cation and intercalation ordering in Li xCoO 2

NASA Astrophysics Data System (ADS)

Wolverton, C.; Zunger, Alex

Several types of cation- and vacancy-ordering are of interest in the Li xCoO 2 battery cathode material since they can have a profound effect on the battery voltage. We present a first-principles theoretical approach which can be used to calculate both cation- and vacancy-ordering patterns at both zero and finite temperatures. This theory also provides quantum-mechanical predictions (i.e., without the use of any experimental input) of battery voltages of both ordered and disordered Li xCoO 2/Li cells from the energetics of the Li intercalation reactions. Our calculations allow us to search the entire configurational space to predict the lowest-energy ground-state structures, search for large voltage cathodes, explore metastable low-energy states, and extend our calculations to finite temperatures, thereby searching for order-disorder transitions and states of partial disorder. We present the first prediction of the stable spinel structure LiCo 2O 4 for the 50% delithiated Li 0.5CoO 2.

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator.

PubMed

Charpentier, Sophie; Galletti, Luca; Kunakova, Gunta; Arpaia, Riccardo; Song, Yuxin; Baghdadi, Reza; Wang, Shu Min; Kalaboukhov, Alexei; Olsson, Eva; Tafuri, Francesco; Golubev, Dmitry; Linder, Jacob; Bauch, Thilo; Lombardi, Floriana

2017-12-08

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral p x  + ip y wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi 2 Te 3 topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral p x  + ip y component. The magnetic field pattern of the junctions shows a dip at zero externally applied magnetic field, which is an incontrovertible signature of the simultaneous existence of 0 and π coupling within the junction, inherent to a non trivial order parameter phase. The nano-textured morphology of the Bi 2 Te 3 flakes, and the dramatic role played by thermal strain are the surprising key factors for the display of an unconventional induced order parameter.

Computing sparse derivatives and consecutive zeros problem

NASA Astrophysics Data System (ADS)

Chandra, B. V. Ravi; Hossain, Shahadat

2013-02-01

We describe a substitution based sparse Jacobian matrix determination method using algorithmic differentiation. Utilizing the a priori known sparsity pattern, a compression scheme is determined using graph coloring. The "compressed pattern" of the Jacobian matrix is then reordered into a form suitable for computation by substitution. We show that the column reordering of the compressed pattern matrix (so as to align the zero entries into consecutive locations in each row) can be viewed as a variant of traveling salesman problem. Preliminary computational results show that on the test problems the performance of nearest-neighbor type heuristic algorithms is highly encouraging.

Kinematics, structural mechanics, and design of origami structures with smooth folds

NASA Astrophysics Data System (ADS)

Peraza Hernandez, Edwin Alexander

Origami provides novel approaches to the fabrication, assembly, and functionality of engineering structures in various fields such as aerospace, robotics, etc. With the increase in complexity of the geometry and materials for origami structures that provide engineering utility, computational models and design methods for such structures have become essential. Currently available models and design methods for origami structures are generally limited to the idealization of the folds as creases of zeroth-order geometric continuity. Such an idealization is not proper for origami structures having non-negligible thickness or maximum curvature at the folds restricted by material limitations. Thus, for general structures, creased folds of merely zeroth-order geometric continuity are not appropriate representations of structural response and a new approach is needed. The first contribution of this dissertation is a model for the kinematics of origami structures having realistic folds of non-zero surface area and exhibiting higher-order geometric continuity, here termed smooth folds. The geometry of the smooth folds and the constraints on their associated kinematic variables are presented. A numerical implementation of the model allowing for kinematic simulation of structures having arbitrary fold patterns is also described. Examples illustrating the capability of the model to capture realistic structural folding response are provided. Subsequently, a method for solving the origami design problem of determining the geometry of a single planar sheet and its pattern of smooth folds that morphs into a given three-dimensional goal shape, discretized as a polygonal mesh, is presented. The design parameterization of the planar sheet and the constraints that allow for a valid pattern of smooth folds and approximation of the goal shape in a known folded configuration are presented. Various testing examples considering goal shapes of diverse geometries are provided. Afterwards, a model for the structural mechanics of origami continuum bodies with smooth folds is presented. Such a model entails the integration of the presented kinematic model and existing plate theories in order to obtain a structural representation for folds having non-zero thickness and comprised of arbitrary materials. The model is validated against finite element analysis. The last contribution addresses the design and analysis of active material-based self-folding structures that morph via simultaneous folding towards a given three-dimensional goal shape starting from a planar configuration. Implementation examples including shape memory alloy (SMA)-based self-folding structures are provided.

Exact sum rules for inhomogeneous systems containing a zero mode

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

Amore, Paolo, E-mail: paolo.amore@gmail.com

2014-10-15

We show that the formulas for the sum rules for the eigenvalues of inhomogeneous systems that we have obtained in two recent papers are incomplete when the system contains a zero mode. We prove that there are finite contributions of the zero mode to the sum rules and we explicitly calculate the expressions for the sum rules of order one and two. The previous results for systems that do not contain a zero mode are unaffected. - Highlights: • We discuss the sum rules of the eigenvalues of inhomogeneous systems containing a zero mode. • We derive the explicit expressionsmore » for sum rules of order one and two. • We perform accurate numerical tests of these results for three examples.« less

Floating-pulsatile release multiparticulate system for chronopharmacotherapy: effect of some hydrophobic additives on the buoyancy and release behavior of particles.

PubMed

Maghsoodi, M

2014-01-01

A blend of floating and pulsatile principles of a drug delivery system would have the advantage that a drug can be released in the upper gastrointestinal (GI) tract after a lag period, which is anticipated for chronotherapy. In this study, microballoons were prepared by an emulsion solvent diffusion technique using Eudragit S100, and hydrophobic additive (magnesium stearate, stearic acid or talc) for time- and site-specific drug release of piroxicam. The effect of hydrophobic additives on the production yield of floating microparticles, buoyant ability for 8 h, release of drug in simulated GI fluids (simulated gastric fluid [SGF] and simulated intestinal fluid [SIF]), mean particle size, apparent particle density, encapsulation efficiency of drug and physical state of incorporated drug were studied. Both production yield and buoyancy of the microballoons were affected by additives in the following order: magnesium stearate, stearic acid>free-additive>talc. The observed difference in yield and the buoyancy of the microballoons could be attributed to the hydrophobic character of the additives and the shell rigidity of the obtained microballoons. Incorporation of hydrophobic additives in the microballoons was found to impart the desired release properties to the microballoons by providing a 2-phase release pattern with initial slow release (5-6%) through 8 h in SGF followed by rapid pulse release (>92%) in SIF through 15 min. The microballoons co-formulated with magnesium stearate or stearic acid, combining excellent buoyancy and suitable drug release pattern of piroxicam, could be useful in chronopharmacotherapy in arthritis. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis of poly(N-isopropylacrylamide)-co-poly(phenylboronate ester) acrylate and study on their glucose-responsive behavior.

PubMed

Yao, Yuan; Shen, Heyun; Zhang, Guanghui; Yang, Jing; Jin, Xu

2014-10-01

We introduced thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) into the polymer structure of poly(ethylene glycol)-block-poly(phenylboronate ester) acrylate (MPEG-block-PPBDEMA) by block and random polymerization pathways in order to investigate the effect of polymer architecture on the glucose-responsiveness and enhance their insulin release controllability. By following the structure, the continuous PNIPAM shell of the triblock polymer MPEG-block-PNIPAM-block-PPBDEMA collapsing on the glucose-responsive PPBDEMA core formed the polymeric micelles with a core-shell-corona structure, and MPEG-block-(PNIPAM-rand-PPBDEMA) exhibited core-corona micelles in which the hydrophobic core consisted of PNIPAM and PPBDEMA segments when the environmental temperature was increased above low critical solution temperature (LCST) of PNIPAM. The micellar morphologies can be precisely controlled by temperature change between 15 and 37°C. As a result, the introduction of PNIPAM greatly enhanced the overall stability of insulin encapsulated in the polymeric micelles in the absence of glucose over incubation 80 h at 37°C. Comparing to MPEG-block-PNIPAM-block-PPBDEMA, the nanocarriers from MPEG-block-(PNIPAM-rand-PPBDEMA) showed great insulin release behavior which is zero insulin release without glucose, low release at normal blood glucose concentration (1.0 mg/mL). Therefore, these nanocarriers may be served as promising self-regulated insulin delivery system for diabetes treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

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

Kruisbrink, J.; Boer, G.J.

1984-12-01

Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin.more » The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero.« less

Gamma scintigraphic evaluation of floating gastroretentive tablets of metformin HCl using a combination of three natural polymers in rabbits

PubMed Central

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Chung, Lip Yong; Nyamathulla, Shaik; Noordin, Mohamed Ibrahim

2015-01-01

The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1–F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug-release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeled using samarium (III) oxide (153Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics. PMID:26273196

A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

PubMed

Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

2008-01-01

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole.

PubMed

van Iersel, Marlou L P S; Rossenu, Stefaan; de Greef, Rik; Waskin, Hetty

2018-04-30

A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid tablet formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia vs allogeneic hematopoietic stem cell transplantation), body weight, and formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (single dose vs multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid tablet formulation provides adequate target therapeutic exposure (>0.5 mg/l) to a broad range of patients at high risk for invasive fungal disease. Copyright © 2018 American Society for Microbiology.

76 FR 20412 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

... least one dollar. With respect to the rebate for Zero Display Orders that add liquidity in AutoEx that... in the Automatic Execution Mode of order interaction (``AutoEx'') \\3\\ priced at least one dollar. Certain conforming changes are also proposed for rebates for liquidity adding Zero Display Orders \\4\\ in...

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

PubMed Central

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L.

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPγS > UDP >> MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release. Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release. PMID:28751862

UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells.

PubMed

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca 2+ -dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca 2+ imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca 2+ oscillations in BON. UTP evoked a biphasic concentration-dependent Ca 2+ response. Cells responded in the order of UTP, ATP > UTPγS > UDP > MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y 4 , 50% cells), UDP (P2Y 6 , 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca 2+ responses were blocked with inhibitors of PLC, IP3R, SERCA Ca 2+ pump, La 3+ sensitive Ca 2+ channels or chelation of intracellular free Ca 2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca 2+ pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca 2+ currents (I Ca ), V m -depolarization and inhibited I K (not I A ) currents. An I Kv 7.2/7.3 K + channel blocker XE-991 mimicked UTP-induced V m -depolarization and blocked UTP-responses. XE-991 blocked I K and UTP caused further reduction. La 3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca 2+ buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y 4 /P2Y 6 R. Zero-Ca 2+ buffer augmented Ca 2+ responses and 5-HT release. Conclusion: UTP activates a predominant P2Y 4 R pathway to trigger Ca 2+ oscillations via internal Ca 2+ mobilization through a PLC/IP 3 /IP3R/SERCA Ca 2+ signaling pathway to stimulate 5-HT release; Ca 2+ influx is inhibitory. UTP-induced V m -depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca 2+ oscillations or I ca /VOCC). UTP-gated signaling pathways triggered by activation of P2Y 4 R stimulate 5-HT release.

Atmospheric Turbulence Modeling for Aerospace Vehicles: Fractional Order Fit

NASA Technical Reports Server (NTRS)

Kopasakis, George (Inventor)

2015-01-01

An improved model for simulating atmospheric disturbances is disclosed. A scale Kolmogorov spectral may be scaled to convert the Kolmogorov spectral into a finite energy von Karman spectral and a fractional order pole-zero transfer function (TF) may be derived from the von Karman spectral. Fractional order atmospheric turbulence may be approximated with an integer order pole-zero TF fit, and the approximation may be stored in memory.

The main beam correction term in kinetic energy release from metastable peaks.

PubMed

Petersen, Allan Christian

2017-12-01

The correction term for the precursor ion signal width in determination of kinetic energy release is reviewed, and the correction term is formally derived. The derived correction term differs from the traditionally applied term. An experimental finding substantiates the inaccuracy in the latter. The application of the "T-value" to study kinetic energy release is found preferable to kinetic energy release distributions when the metastable peaks are slim and simple Gaussians. For electronically predissociated systems, a "borderline zero" kinetic energy release can be directly interpreted in reaction dynamics with strong curvature in the reaction coordinate. Copyright © 2017 John Wiley & Sons, Ltd.

Leveraging Technology to Support the Army’s Net Zero Installation Initiative

DTIC Science & Technology

2012-05-23

No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing...MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES...350,000 400,000 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Biomass Wind Geothermal PV Solar Hot Water Propane Electrical Grid Net Zero Water

Do soft drinks affect metal ions release from orthodontic appliances?

PubMed

Mikulewicz, Marcin; Wołowiec, Paulina; Loster, Bartłomiej W; Chojnacka, Katarzyna

2015-01-01

The effect of orange juice and Coca Cola(®) on the release of metal ions from fixed orthodontic appliances. A continuous flow system designed for in vitro testing of orthodontic appliances was used. Orange juice/Coca Cola(®) was flowing through the system alternately with artificial saliva for 5.5 and 18.5h, respectively. The collected samples underwent a multielemental ICP-OES analysis in order to determine the metal ions release pattern in time. The total mass of ions released from the appliance into orange juice and Coca Cola(®) (respectively) during the experiment was calculated (μg): Ni (15.33; 37.75), Cr (3.604; 1.052), Fe (48.42; ≥ 156.1), Cu (57.87, 32.91), Mn (9.164; 41.16), Mo (9.999; 30.12), and Cd (0.5967; 2.173). It was found that orange juice did not intensify the release of metal ions from orthodontic appliances, whereas Coca Cola(®) caused increased release of Ni ions. Copyright © 2015 Elsevier GmbH. All rights reserved.

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

Continuous fractional-order Zero Phase Error Tracking Control.

PubMed

Liu, Lu; Tian, Siyuan; Xue, Dingyu; Zhang, Tao; Chen, YangQuan

2018-04-01

A continuous time fractional-order feedforward control algorithm for tracking desired time varying input signals is proposed in this paper. The presented controller cancels the phase shift caused by the zeros and poles of controlled closed-loop fractional-order system, so it is called Fractional-Order Zero Phase Tracking Controller (FZPETC). The controlled systems are divided into two categories i.e. with and without non-cancellable (non-minimum-phase) zeros which stand in unstable region or on stability boundary. Each kinds of systems has a targeted FZPETC design control strategy. The improved tracking performance has been evaluated successfully by applying the proposed controller to three different kinds of fractional-order controlled systems. Besides, a modified quasi-perfect tracking scheme is presented for those systems which may not have available future tracking trajectory information or have problem in high frequency disturbance rejection if the perfect tracking algorithm is applied. A simulation comparison and a hardware-in-the-loop thermal peltier platform are shown to validate the practicality of the proposed quasi-perfect control algorithm. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Planetary Patterns. Grade 8 Science, Language Usage. Maryland School Performance Assessment Program (MSPAP): Resource Library. Public Release Task.

ERIC Educational Resources Information Center

Maryland State Dept. of Education. Baltimore. Div. of Planning, Results and Information Management.

One component of the Maryland School Performance Assessment Program (MSPAP) is the state's performance-based assessments, criterion-referenced tests that require students to apply what they know and can do to solve problems and display other higher-order thinking skills. This document helps parents, teachers, students, and other citizens…

NASA Net Zero Energy Buildings Roadmap

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

Pless, S.; Scheib, J.; Torcellini, P.

In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategicmore » approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.« less

Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

NASA Astrophysics Data System (ADS)

Nguyen, Thao M.

Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes, while the control showed no visible drugs at the same depth. Most importantly, it was determined that the delivery of drugs into the blood stream was stable within 20 minutes. The functionalization of CP was also studied in order to enhance the properties and drug loading capabilities of the polymers. The co-polymerization of poly(3,4-(2-methylene)propylenedioxythiophene) (PMProDot) with polystyrene (PS) and polyvinylcarbazole (PVK) through the highly reactive methylene group was achieved. The modified PMProDot nanotubes demonstrated response times that were two times faster than without modification. The modification of PEDOT nanotubes with polydopamine, a biocompatible polymer, was also investigated and achieved. In depth characterization of functionalized CP demonstrate the ability to fine tune the properties of the polymer in order to achieve the required therapeutic drug release profile.

Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

PubMed

Bendas, Ehab R; Christensen, J Mark; Ayres, James W

2010-04-01

The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

Somatodendritic dopamine release: recent mechanistic insights

PubMed Central

Rice, Margaret E.; Patel, Jyoti C.

2015-01-01

Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

Coulomb gauge ghost Dyson-Schwinger equation

NASA Astrophysics Data System (ADS)

Watson, P.; Reinhardt, H.

2010-12-01

A numerical study of the ghost Dyson-Schwinger equation in Coulomb gauge is performed and solutions for the ghost propagator found. As input, lattice results for the spatial gluon propagator are used. It is shown that in order to solve completely, the equation must be supplemented by a nonperturbative boundary condition (the value of the inverse ghost propagator dressing function at zero momentum), which determines if the solution is critical (zero value for the boundary condition) or subcritical (finite value). The various solutions exhibit a characteristic behavior where all curves follow the same (critical) solution when going from high to low momenta until forced to freeze out in the infrared to the value of the boundary condition. The renormalization is shown to be largely independent of the boundary condition. The boundary condition and the pattern of the solutions can be interpreted in terms of the Gribov gauge-fixing ambiguity. The connection to the temporal gluon propagator and the infrared slavery picture of confinement is explored.

Universal Pin Electronics.

DTIC Science & Technology

1982-11-03

define the maximum count for the pattern defined by the first 3 bits. Since there are 11 bits involved it is possible to define patterns up to 2048 ...applied to the UUT directly through the driver for any count up to 2048 . Any one of the 7 clocks may be selected under program control and applied to any...one ievel for the driver ( VDI ), the logic zero level for the driver (VDO), the logic one level for the receiver (VRl), and the logic zero level for the

Binary Black Holes and Gravitational Waves

NASA Technical Reports Server (NTRS)

Centrella, Joan

2007-01-01

The final merger of two black holes releases a tremendous amount of energy, more than the combined light from all the stars in the visible universe. This energy is emitted in the form of gravitational waves, and observing these sources with gravitational wave detectors such as LIGO and LISA requires that we know the pattern or fingerprint of the radiation emitted. Since black hole mergers take place in regions of extreme gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these wave patterns.

Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

NASA Astrophysics Data System (ADS)

Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

2018-02-01

Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

Epiphytic cryptogams as a source of bioaerosols and trace gases

NASA Astrophysics Data System (ADS)

Ruckteschler, Nina; Hrabe de Angelis, Isabella; Zartman, Charles E.; Araùjo, Alessandro; Pöschl, Ulrich; Manzi, Antonio O.; Andreae, Meinrat O.; Pöhlker, Christopher; Weber, Bettina

2016-04-01

Cryptogamic covers comprise (cyano-)bacteria, algae, lichens, bryophytes, fungi, and archaea in varying proportions. These organisms do not form flowers, but reproduce by spores or cell cleavage with these reproductive units being dispersed via the atmosphere. As so-called poikilohydric organisms they are unable to regulate their water content, and their physiological activity pattern mainly follows the external water conditions. We hypothesize, that both spore dispersal and the release of trace gases are governed by the moisture patterns of these organisms and thus they could have a greater impact on the atmosphere than previously thought. In order to test this hypothesis, we initiated experiments at the study site Amazonian Tall Tower Observatory (ATTO) in September 2014. We installed microclimate sensors in epiphytic cryptogams at four different heights of a tree to monitor the activity patterns of these organisms. Self-developed moisture probes are used to analyze the water status of the organisms accompanied by light and temperature sensors. The continuously logged data are linked to ongoing measurements of trace gases and particulate bioaerosols to analyze these for the relevance of cryptogams. Here, we are particularly interested in diurnal cycles of coarse mode particles and the atmospheric abundance of fine potassium-rich particles from a currently unknown biogenic source. Based upon the results of this field study we also investigate the bioaerosol and trace gas release patterns of cryptogamic covers under controlled conditions. With this combined approach of field and laboratory experiments we aim to disclose the role of cryptogamic covers in bioaerosol and trace gas release patterns in the Amazonian rainforest.

Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature.

PubMed

Kapteijns-van Kordelaar, Simone; Noordam, Kees; Otten, Barto; van den Bergh, Joop

2003-11-01

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean age at start 7.4 years) and group B (n=11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2-L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above -1 in both groups (group A: BUA Z-score -0.21, SOS Z-score -0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score -0.93, SOS Z-score -0.40, BMD Z-score -0.86, BMDvol Z-score -0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero (P=0.03 and P=0.02 respectively). Mean Z-score BMDvol was not significantly different from zero (P=0.05), we found no significant difference between the groups for BMDvol (P=0.13). Although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.

Teacher in Space Christa McAuliffe on the KC-135 for zero-G training

NASA Image and Video Library

1986-01-08

S86-25191 (for release January 1986) --- The two representatives of the Teacher-in-Space Project continue their training program at the Johnson Space Center with an additional flight aboard NASA?s KC-135 ?zero gravity? aircraft. Sharon Christa McAuliffe, left, is prime crew payload specialist, and Barbara R. Morgan is in training as backup payload specialist. The photo was taken by Keith Meyers of New York Times. Photo credit: NASA

Implications of loading/unloading a subduction zone with a heterogeneously coupled interface

NASA Astrophysics Data System (ADS)

Herman, M. W.; Furlong, K. P.; Govers, R. M. A.

2017-12-01

Numerical models of subduction zones with appropriate physical properties may help understand deformation throughout great earthquake cycles, as well as associated observations such as the distribution of smaller magnitude megathrust earthquakes and surface displacements. Of particular interest are displacements near the trench, where tsunamis are generated. The patterns of co-seismic strain release in great megathrust earthquakes depend on the frictional coupling of the plate interface prior to the event. Geodetic observations during the inter-seismic stage suggest that the plates are fully locked at asperities surrounded by zones of apparent partial coupling. We simulate the accumulation (and release) of elastic strain in the subduction system using a finite element model with a relatively simple geometry and material properties. We demonstrate that inter-seismic apparent partial coupling can be dominantly explained by a distribution of completely locked asperities and zero friction elsewhere. In these models, the interface up-dip of the locked zone (< 15 km depth) accumulates large slip deficit even if its coefficient of friction is zero, as might be inferred from the scarcity of megathrust earthquakes shallower than 15 km in global earthquake catalogs. In addition, the upper plate above a low-friction shallow megathrust accumulates large displacements with little internal strain, potentially leading to large co-seismic block displacements (low displacement gradients) of the near-trench seafloor like those observed following the 2011 Mw 9.0 Tohoku earthquake. This is also consistent with anomalously low co-seismic frictional heating of the shallow megathrust indicated by borehole heat flow measurements after the Tohoku event. Our models also yield insights into slip partitioning throughout multiple earthquake cycles. In smaller ruptures, fault slip is inhibited by nearby locked zones; in subsequent multi-segment ruptures, the rest of this slip deficit may be released, producing significantly larger slip than might be expected based on historical earthquake magnitudes. Finally, because low-friction areas around asperities accumulate some slip deficit but may not rupture co-seismically, these regions may be the primary locations of afterslip following the rupture of the locked patch.

Path-Integral Monte Carlo Determination of the Fourth-Order Virial Coefficient for a Unitary Two-Component Fermi Gas with Zero-Range Interactions

NASA Astrophysics Data System (ADS)

Yan, Yangqian; Blume, D.

2016-06-01

The unitary equal-mass Fermi gas with zero-range interactions constitutes a paradigmatic model system that is relevant to atomic, condensed matter, nuclear, particle, and astrophysics. This work determines the fourth-order virial coefficient b4 of such a strongly interacting Fermi gas using a customized ab initio path-integral Monte Carlo (PIMC) algorithm. In contrast to earlier theoretical results, which disagreed on the sign and magnitude of b4 , our b4 agrees within error bars with the experimentally determined value, thereby resolving an ongoing literature debate. Utilizing a trap regulator, our PIMC approach determines the fourth-order virial coefficient by directly sampling the partition function. An on-the-fly antisymmetrization avoids the Thomas collapse and, combined with the use of the exact two-body zero-range propagator, establishes an efficient general means to treat small Fermi systems with zero-range interactions.

A Hybrid Methacrylate-Sodium Carboxymethylcellulose Interpolyelectrolyte Complex: Rheometry and in Silico Disposition for Controlled Drug Release

PubMed Central

Ngwuluka, Ndidi Chinyelu; Choonara, Yahya Essop; Kumar, Pradeep; Modi, Girish; du Toit, Lisa Claire; Pillay, Viness

2013-01-01

The rheological behavioral changes that occurred during the synthesis of an interpolyelectrolyte complex (IPEC) of methacrylate copolymer and sodium carboxymethylcellulose were assessed. These changes were compared with the rheological behavior of the individual polymers employing basic viscosity, yield stress, stress sweep, frequency sweep, temperature ramp as well as creep and recovery testing. The rheological studies demonstrated that the end-product of the complexation of low viscous methacrylate copolymer and entangled solution of sodium carboxymethylcellulose generated a polymer, which exhibited a solid-like behavior with a three-dimensional network. Additionally, the rheological profile of the sodium carboxymethylcellulose and methacrylate copolymer with respect to the effect of various concentrations of acetic acid on the synthesis of the IPEC was elucidated using molecular mechanics energy relationships (MMER) by exploring the spatial disposition of carboxymethylcellulose and methacrylate copolymer with respect to each other and acetic acid. The computational results corroborated well with the experimental in vitro drug release data. Results have shown that the IPEC may be suitable polymeric material for achieving controlled zero-order drug delivery. PMID:28788332

Laser Printing of PCL/Progesterone Tablets for Drug Delivery Applications in Hormone Cancer Therapy

NASA Astrophysics Data System (ADS)

Salmoria, G. V.; Klauss, P.; Kanis, L. A.

2017-09-01

In this study, polycaprolactone (PCL) and progesterone (PG) tablets were produced by selective laser sintering (SLS) using different particle sizes and laser energy. The sintered PCL/PG tablets presented uniform morphology, coalescence of particles and interconnected pores distributed in the polymeric matrix. The EDS analysis confirmed the presence of progesterone recrystallized on the surface of the porous PCL matrix. The crystallinity values for the PCL/PG tablets were lower than that for the pure PCL, suggesting the interaction of components at the molecular level. The PCL/PG tablets fabricated with small particles and high laser energy presented a higher value for the flexural modulus compared with the other specimens. The glass transition temperature (Tg) was -37 °C for the PCL/PG tablet with a high degree of sintering. The fatigue test showed that the PCL/PG blend tablets have high fatigue strength. The drug release mechanism of all tablets studied followed a zero-order kinetics, and drug release rates were dependent on sintering degree and, consequently, on matrix erosion, showing a potential application to controlled drug delivery in hormone cancer therapy.

Geophysical disturbance environment during the NASA/MPE barium release at 5 earth radii on September 21, 1971.

NASA Technical Reports Server (NTRS)

Davis, T. N.; Stanley, G. M.; Boyd, J. S.

1973-01-01

The geophysical disturbance environment was quiet during the NASA/MPE barium release at 5 earth radii on September 21, 1971. At the time of the release, the magnetosphere was in the late recovery phase of a principal magnetic storm, the provisional Dst value was -13 gammas, and the local horizontal disturbance at Great Whale River was near zero. Riometer and other observations indicated low-level widespread precipitation of high-energy electrons at Great Whale River before, during, and after the release. Cloudy sky at this station prevented optical observation of aurora. No magnetic or ionospheric effects attributable to the barium release were detected at Great Whale River.

Degradation of trichloroethylene (TCE) by nanoscale zero-valent iron (nZVI) immobilized in alginate bead.

PubMed

Kim, Hojeong; Hong, Hye-Jin; Jung, Juri; Kim, Seong-Hye; Yang, Ji-Won

2010-04-15

Nowadays, many researchers have studied the environmental application of the nanoscale zero-valent iron (nZVI) and several field applications for the groundwater remediation have been reported. Still, there are many concerns on the fate and transport of the nZVI and the corresponding risks. To avoid such concerns, it was investigated to immobilize nZVI in a support and then it was applied to degrade trichloroethylene (TCE). The nZVI and palladium-doped nZVI (Fe(0)- and Fe/Pd-alginate) were immobilized in the alginate bead where ferric and barium ions are used as the cross-linking cations of the bead. According to TEM (transmission electron microscopy), the size of the immobilized ZVI was as small as a few nanometers. From the surface analysis of the Fe/Pd-alginate, it is found that the immobilized nZVI has the core-shell structure. The core is composed of single crystal Fe(0), while most of irons on the surface are oxidized to Fe(3+). When 50 g/L of Fe/Pd-alginate (3.7 g Fe/L) was introduced to the aqueous solution, >99.8% of TCE was removed and the release of metal from the support was <3% of the loaded iron. The removal of TCE by Fe/Pd-alginate followed pseudo-first-order kinetics. The observed pseudo-first-order reaction constant (k(obs)) of Fe/Pd-alginate was 6.11 h(-1) and the mass normalized rate constant (k(m)) was 1.6 L h(-1) g(-1). The k(m) is the same order of magnitude with that of iron nanoparticles. In conclusion, it is considered that Fe/Pd-alginate can be used efficiently in the treatment of chlorinated solvent. 2009 Elsevier B.V. All rights reserved.

Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

PubMed

Loh, Zhiao C; Elkordy, Amal A

2015-01-01

The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.

Hydrophilic absorbable copolyester exhibiting zero-order drug release.

PubMed

Andjelić, Sasa; Yuan, Jenny; Jamiolkowski, Dennis D; Diluccio, Robert; Bezwada, Rao; Zhang, Hua; Mijović, Jovan

2006-04-01

A novel absorbable hydrophilic copolyester developed in our laboratory, amorphous 40/60 poly(ethylene diglycolate-co-glycolide), exhibits outstanding physical properties. Films made from this material appear fully transparent, colorless, soft and slightly elastic, but relatively strong and durable materials so that they can be potentially used as stand-alone devices in various in-vivo medical applications. In this study, in-vitro drug release characteristics of this copolyester were examined. High Performance Liquid Chromatography was used to generate release profiles on selected non-steroidal anti-inflammatory agents, NSAIDs. In addition, dielectric relaxation spectroscopy, as well as mid- and near infrared spectroscopy, were used to study specific polymer chain interactions in water and buffer solution as a function of aging time at 37 degrees C. This copolyester, compression molded into a film, exhibited nearly constant in-vitro release of various hydrophilic and hydrophobic drugs. The release profile showed minimal or, in most cases, no burst effect. The effect was observed with the three NSAIDs that were tested as model compounds; however, this system may prove generally useful for other drug entities. In-vitro hydrolysis conducted at 37 degrees C on this hydrophilic copolyester revealed an unusually long induction period (no hydrolysis for up to 6 days), followed by the relatively rapid hydrolysis. Data from dipole relaxation spectroscopy indicated that the water molecules do not structurally associate with the polymer chains in phosphate buffer during initial hydrolysis period. The results suggest unique dynamics of water diffusion through the polymer matrix that may play a critical role in achieving controlled release properties. Furthermore, we suspect that the molecular interactions associated with this new synthetic absorbable material may find a critical utility in important medical applications.

Kinetics of abiotic nitrous oxide production via oxidation of hydroxylamine by particulate metals in seawater

NASA Astrophysics Data System (ADS)

Cavazos, A. R.; Taillefert, M.; Glass, J. B.

2016-12-01

The oceans are a significant of nitrous oxide (N2O) to the atmosphere. Current models of global oceanic N2­O flux focus on microbial N2O cycling and often ignore abiotic reactions, such as the thermodynamically favorable oxidation of the nitrification intermediate hydroxylamine (NH2OH) by Mn(IV) or Fe(III). At circumneutral pH, NH2OH oxidation is more thermodynamically favorable via Mn(IV) than Fe(III) reduction. We characterized the kinetics of NH2OH oxidation in synthetic ocean water at pH 5.1-8.8 using microsensor electrodes to measure real-time N2O production. N2O production rates and yield were greater when NH2OH was oxidized by Mn(IV) than Fe(III). Accordingly, the reduction of Mn(IV) was first order with respect to NH2OH whereas the reduction of Fe(III) was zero order with respect to NH2OH. Interestingly, the order of the reaction with respect to Mn(IV) appears to be negative whereas the reaction is second order with respect to Fe(III). The inverse order with respect to Mn(IV) may be due to the aggregation of particles in seawater, which decreases their surface area and changes their reactivity. Finally, the reaction is first order with respect to protons with Fe(III) as the oxidant but zero order with Mn(IV). The stronger effect of the pH on the reaction with Fe(III) as the oxidant compared to Mn(IV) reflects the stoichiometry of these two reactions, as each mole of N2O produced by Fe(III) reduction consumes eight protons while each mole of N2O produced with Mn(IV) as the oxidant requires only four protons. Our data show that abiotic NH2OH oxidation by Mn(IV) or Fe(III) particles may represent a significant source of N2O in seawater. These findings suggest that abiotic N2O production in marine waters may be significant in areas of the oceans where particulate metals originating from aerosols, dust, or rivers may react with NH2OH released from ammonia-oxidizing microorganisms.

Breather solutions of a fourth-order nonlinear Schrödinger equation in the degenerate, soliton, and rogue wave limits

NASA Astrophysics Data System (ADS)

Chowdury, Amdad; Krolikowski, Wieslaw; Akhmediev, N.

2017-10-01

We present one- and two-breather solutions of the fourth-order nonlinear Schrödinger equation. With several parameters to play with, the solution may take a variety of forms. We consider most of these cases including the general form and limiting cases when the modulation frequencies are 0 or coincide. The zero-frequency limit produces a combination of breather-soliton structures on a constant background. The case of equal modulation frequencies produces a degenerate solution that requires a special technique for deriving. A zero-frequency limit of this degenerate solution produces a rational second-order rogue wave solution with a stretching factor involved. Taking, in addition, the zero limit of the stretching factor transforms the second-order rogue waves into a soliton. Adding a differential shift in the degenerate solution results in structural changes in the wave profile. Moreover, the zero-frequency limit of the degenerate solution with differential shift results in a rogue wave triplet. The zero limit of the stretching factor in this solution, in turn, transforms the triplet into a singlet plus a low-amplitude soliton on the background. A large value of the differential shift parameter converts the triplet into a pure singlet.

Breather solutions of a fourth-order nonlinear Schrödinger equation in the degenerate, soliton, and rogue wave limits.

PubMed

Chowdury, Amdad; Krolikowski, Wieslaw; Akhmediev, N

2017-10-01

We present one- and two-breather solutions of the fourth-order nonlinear Schrödinger equation. With several parameters to play with, the solution may take a variety of forms. We consider most of these cases including the general form and limiting cases when the modulation frequencies are 0 or coincide. The zero-frequency limit produces a combination of breather-soliton structures on a constant background. The case of equal modulation frequencies produces a degenerate solution that requires a special technique for deriving. A zero-frequency limit of this degenerate solution produces a rational second-order rogue wave solution with a stretching factor involved. Taking, in addition, the zero limit of the stretching factor transforms the second-order rogue waves into a soliton. Adding a differential shift in the degenerate solution results in structural changes in the wave profile. Moreover, the zero-frequency limit of the degenerate solution with differential shift results in a rogue wave triplet. The zero limit of the stretching factor in this solution, in turn, transforms the triplet into a singlet plus a low-amplitude soliton on the background. A large value of the differential shift parameter converts the triplet into a pure singlet.

Solutions as solutions--synthesis and use of a liquid polyester excipient to dissolve lipophilic drugs and formulate sustained-release parenterals.

PubMed

Asmus, Lutz R; Gurny, Robert; Möller, Michael

2011-11-01

Solid poly(lactides) and poly(lactide-co-glycolides) are widely used polymers for sustained-release parenterals. However, they have some unfavorable properties regarding manufacturing of the formulations and administration to the patient due to their solid aggregate state. In contrast, hexyl-substituted poly(lactic acid) (hexPLA, poly(2-hydroxyoctanoic acid)) is a viscous degradable polyester. To date, a two-step ring-opening polymerization was used for its synthesis. Here, we investigated a novel one-pot one-step melt polycondensation method to prepare hexPLA for biomedical applications by a simple green chemistry process. No catalyst or solely pharmaceutically acceptable catalysts and environmentally friendly purification methods without organic solvents were used. The resulting hexPLA polymers are stable under dry heat sterilization conditions. Low molecular weight hexPLAs with less than 5000 g/mol are less viscous than high molecular weight polymers. HexPLA can dissolve lipophilic active substances, with generally high incorporation capacities in low molecular weight polymers. The incorporation of solid compounds increases the viscosity and glass transition temperature, whereas the addition of small amounts of plasticizers or sparse warming significantly decreases the viscosity. Loratadine is soluble in hexPLA up to 28%. This highly concentrated Loratadine-hexPLA formulation released the active compound entirely over 14 days without initial burst in a zero order kinetic, matching the clinical requirements for such a sustained-release formulation. This demonstrates the potential of hexPLA as an excipient for injectable sustained-release formulations. Copyright © 2011 Elsevier B.V. All rights reserved.

Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

PubMed Central

Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

2014-01-01

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053

3D-micro-patterned fibrous dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-03-01

At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

Gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan: optimization and release characteristics.

PubMed

Lee, Ji-Soo; Kim, Jong Soo; Lee, Hyeon Gyu

2009-05-01

Response surface methodology was used to optimize microparticle preparation conditions, including the ratio of pectin:gamma-oryzanol (OZ) (X(1)), agitation speed (X(2)), and the concentration of emulsifier (X(3)), for maximal entrapment efficiency (EE) of OZ-loaded Ca pectinate microparticles. The optimized values of X(1), X(2), and X(3) were found to be 2.72:5.28, 1143.5 rpm, and 2.61%, respectively. Experimental results obtained for the optimum formulation agreed favorably with the predicted results, indicating the usefulness of predicting models for EE. In order to evaluate the effect of chitosan-coating and blending on the release pattern of the entrapped OZ from microparticles, chitosan-coated and blended Ca pectinate microparticles were prepared. Release studies revealed that the chitosan treatments, especially the chitosan-coating, were effective in suppressing the release in both simulated gastric fluid (SGF) and intestinal fluid (SIF).

Instant release fraction corrosion studies of commercial UO2 BWR spent nuclear fuel

NASA Astrophysics Data System (ADS)

Martínez-Torrents, Albert; Serrano-Purroy, Daniel; Sureda, Rosa; Casas, Ignasi; de Pablo, Joan

2017-05-01

The instant release fraction of a spent nuclear fuel is a matter of concern in the performance assessment of a deep geological repository since it increases the radiological risk. Corrosion studies of two different spent nuclear fuels were performed using bicarbonate water under oxidizing conditions to study their instant release fraction. From each fuel, cladded segments and powder samples obtained at different radial positions were used. The results were normalised using the specific surface area to permit a comparison between fuels and samples. Different radionuclide dissolution patterns were studied in terms of water contact availability and radial distribution in the spent nuclear fuel. The relationship between the results of this work and morphological parameters like the grain size or irradiation parameters such as the burn-up or the linear power density was studied in order to increase the understanding of the instant release fraction formation.

Kinetics of mineralization of organic compounds at low concentrations in soil.

PubMed Central

Scow, K M; Simkins, S; Alexander, M

1986-01-01

The kinetics of mineralization of 14C-labeled phenol and aniline were measured at initial concentrations ranging from 0.32 to 5,000 ng and 0.30 ng to 500 micrograms/g of soil, respectively. Mineralization of phenol at concentrations less than or equal to 32 ng/g of soil and of aniline at all concentrations began immediately, and the curves for the evolution of labeled CO2 were biphasic. The patterns of mineralization of 4.0 ng of 2,4-dichlorophenol per g of soil and 20 ng of nitrilotriacetic acid per g of soil were similar to the patterns for phenol and aniline. The patterns of mineralization of 1.0 to 100 ng of p-nitrophenol and 6.0 ng of benzylamine per g of soil were also biphasic but after a short apparent lag period. The curves of CO2 evolution from higher concentrations of phenol and p-nitrophenol had increasing apparent lag phases and were S-shaped or linear. Cumulative plots of the percentage of substrate converted to CO2 were fit by nonlinear regression to first-order, integrated Monod, logistic, logarithmic, zero-order, three-half-order, and two-compartment models. None of the models of the Monod family provided the curve of best fit to any of the patterns of mineralization. The linear growth form of the three-half-order model provided the best fit for the mineralization of p-nitrophenol, with the exception of the lowest concentrations, and of benzylamine. The two-compartment model provided the best fit for the mineralization of concentrations of phenol below 100 ng/g, of several concentrations of aniline, and of nitrilotriacetic acid. It is concluded that models derived from the Monod equation, including the first-order model, do not adequately describe the kinetics of mineralization of low concentrations of chemicals added to soil. PMID:3729388

Numerical ordering of zero in honey bees.

PubMed

Howard, Scarlett R; Avarguès-Weber, Aurore; Garcia, Jair E; Greentree, Andrew D; Dyer, Adrian G

2018-06-08

Some vertebrates demonstrate complex numerosity concepts-including addition, sequential ordering of numbers, or even the concept of zero-but whether an insect can develop an understanding for such concepts remains unknown. We trained individual honey bees to the numerical concepts of "greater than" or "less than" using stimuli containing one to six elemental features. Bees could subsequently extrapolate the concept of less than to order zero numerosity at the lower end of the numerical continuum. Bees demonstrated an understanding that parallels animals such as the African grey parrot, nonhuman primates, and even preschool children. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Multi-pulse multi-delay (MPMD) multiple access modulation for UWB

DOEpatents

Dowla, Farid U.; Nekoogar, Faranak

2007-03-20

A new modulation scheme in UWB communications is introduced. This modulation technique utilizes multiple orthogonal transmitted-reference pulses for UWB channelization. The proposed UWB receiver samples the second order statistical function at both zero and non-zero lags and matches the samples to stored second order statistical functions, thus sampling and matching the shape of second order statistical functions rather than just the shape of the received pulses.

Experimental Demonstration of Quantum Stationary Light Pulses in an Atomic Ensemble

NASA Astrophysics Data System (ADS)

Park, Kwang-Kyoon; Cho, Young-Wook; Chough, Young-Tak; Kim, Yoon-Ho

2018-04-01

We report an experimental demonstration of the nonclassical stationary light pulse (SLP) in a cold atomic ensemble. A single collective atomic excitation is created and heralded by detecting a Stokes photon in the spontaneous Raman scattering process. The heralded single atomic excitation is converted into a single stationary optical excitation or the single-photon SLP, whose effective group velocity is zero, effectively forming a trapped single-photon pulse within the cold atomic ensemble. The single-photon SLP is then released from the atomic ensemble as an anti-Stokes photon after a specified trapping time. The second-order correlation measurement between the Stokes and anti-Stokes photons reveals the nonclassical nature of the single-photon SLP. Our work paves the way toward quantum nonlinear optics without a cavity.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

Meshless Local Petrov-Galerkin Method for Solving Contact, Impact and Penetration Problems

DTIC Science & Technology

2006-11-30

Crack Growth 3 point of view, this approach makes the full use of the ex- isting FE models to avoid any model regeneration , which is extremely high in...process, at point C, the pressure reduces to zero, but the volumet- ric strain does not go to zero due to the collapsed void volume. 2.2 Damage...lease rate to go beyond the critical strain energy release rate. Thus, the micro-cracks begin to growth inside these areas. At 10 micro-seconds, these

Vegetation-environment relationships in zero-order basins in coastal Oregon.

Treesearch

Chris D. Sheridan; Thomas A. Spies

2005-01-01

Zero-order basins, where hillslope topography converges to form drainages, are common in steep, forested landscapes but we know little about their ecological structure. We used indirect gradient analysis to characterize gradients in plant species composition and cluster analysis to characterize groups of plant species associated with specific geomorphic areas. We...

Optimization and formulation design of gels of Diclofenac and Curcumin for transdermal drug delivery by Box-Behnken statistical design.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Amin, Saima; Rathee, Permender; Kumar, Vikash

2011-02-01

The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release. Copyright © 2010 Wiley-Liss, Inc.

Diagrams for the Free Energy and Density Weight Factors of the Ising Models.

DTIC Science & Technology

1983-01-01

sum to zero . The associated R. A. Farrell, T. Morita, and P. H. E. Meijer, "Cluster Expan- also, "_ ratum: New Generating Functions and Results for the...given for the cubic lattices. We employ a theorem that states that a certain sum of diagrams is zero in order to obtain the density-dependent weight...these diagrams are given for the cubic lattices. We employ a theorem that states that a certain sum of diagrams is zero in order to obtain the density

Go out or stay in? The effects of zero tolerance laws on alcohol use and drinking and driving patterns among college students.

PubMed

Liang, Lan; Huang, Jidong

2008-11-01

Zero tolerance laws make it illegal per se for anyone under age 21 to drive with any measurable amount of blood alcohol. Although a link has been established between zero tolerance laws and lower motor vehicle fatalities, research has not produced strong evidence on how zero tolerance laws influence individual alcohol use and drinking and driving behaviors. Using a unique data set and a difference-in-difference-in-difference-type research design, we are able to analyze a number of pathways through which zero tolerance laws can work among an important underage population, college students. We find that zero tolerance laws reduce drinking and driving among college students. Further analysis of our detailed alcohol use measures suggests that zero tolerance laws are particularly effective at reducing the probability of driving after drinking for those who reported drinking away from home.

Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits.

PubMed

Tayel, Saadia Ahmed; El-Nabarawi, Mohamed Ahmed; Tadros, Mina Ibrahim; Abd-Elsalam, Wessam Hamdy

2013-02-25

Terbinafine hydrochloride (T-HCl) is recommended for the management of fungal keratitis. To maintain effective aqueous humor concentrations, frequent instillation of T-HCl drops is necessary. This work aimed to develop alternative controlled-release in situ ocular drug-loaded nanoemulsion (NE) gels. Twelve pseudoternary-phase diagrams were constructed using oils (isopropyl myristate/Miglyol 812), surfactants (Tween 80/Cremophor EL), a co-surfactant (polyethylene glycol 400) and water. Eight drug-loaded (0.5%, w/v) NEs were evaluated for thermodynamic stability, morphology, droplet size and drug release in simulated tear fluid (pH 7.4). Following dispersion in gellan gum solution (0.2%, w/w), the in situ NE gels were characterized for transparency, rheological behavior, mucoadhesive force, drug release and histopathological assessment of ocular irritation. Drug pharmacokinetics of sterilized F31 [Miglyol 812, Cremophor EL: polyethylene glycol 400 (1:2) and water (5, 55 and 40%, w/w, respectively)] in situ NE gel and oily drug solution were evaluated in rabbit aqueous humor. The NEs were thermodynamically stable and have spherical droplets (<30 nm). The gels were transparent, pseudoplastic, mucoadhesive and showed more retarded zero-order drug release rates. F31 in situ NE gel showed the least ocular irritation potential and significantly (P<0.01) higher C(max), delayed T(max), prolonged mean residence time and increased bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine

PubMed Central

Mohana Raghava Srivalli, K.; Lakshmi, P.K.; Balasubramaniam, J.

2012-01-01

Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 23 full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 103 dyn/cm2 was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t90% at 6th and 12th hours, respectively. The “n” value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength. PMID:24109205

Simulation of whistler waves excited in the presence of a cold plasma cloud - Implications for the CRRES mission. [Combined Release and Radiation Effects Satellite

NASA Technical Reports Server (NTRS)

Pritchett, P. L.; Schriver, D.; Ashour-Abdalla, M.

1991-01-01

A one-dimensional electromagnetic particle simulation model is constructed to study the excitation of whistler waves in the presence of a cold plasma cloud for conditions representative of those after the release of lithium in the inner plasma sheet during the Combined Release and Radiation Effect Satellite mission. The results indicate that a standing-wave pattern with discrete wave frequencies is formed within the cloud. The magnetic wave amplitude inside the cloud, which is limited by quasi-linear diffusion, is of the order of several nanoteslas. Assuming a magnetospheric loss cone of 5 deg, the observed pitch angle diffusion produced by the whistler waves is sufficient to put the electrons on strong diffusion.

Coarsening of stripe patterns: variations with quench depth and scaling.

PubMed

Tripathi, Ashwani K; Kumar, Deepak

2015-02-01

The coarsening of stripe patterns when the system is evolved from random initial states is studied by varying the quench depth ε, which is a measure of distance from the transition point of the stripe phase. The dynamics of the growth of stripe order, which is characterized by two length scales, depends on the quench depth. The growth exponents of the two length scales vary continuously with ε. The decay exponents for free energy, stripe curvature, and densities of defects like grain boundaries and dislocations also show similar variation. This implies a breakdown of the standard picture of nonequilibrium dynamical scaling. In order to understand the variations with ε we propose an additional scaling with a length scale dependent on ε. The main contribution to this length scale comes from the "pinning potential," which is unique to systems where the order parameter is spatially periodic. The periodic order parameter gives rise to an ε-dependent potential, which can pin defects like grain boundaries, dislocations, etc. This additional scaling provides a compact description of variations of growth exponents with quench depth in terms of just one exponent for each of the length scales. The relaxation of free energy, stripe curvature, and the defect densities have also been related to these length scales. The study is done at zero temperature using Swift-Hohenberg equation in two dimensions.

Thermal emitter comprising near-zero permittivity materials

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

Luk, Ting S.; Campione, Salvatore; Sinclair, Michael B.

A novel thermal source comprising a semiconductor hyperbolic metamaterial provides control of the emission spectrum and the angular emission pattern. These properties arise because of epsilon-near-zero conditions in the semiconductor hyperbolic metamaterial. In particular, the thermal emission is dominated by the epsilon-near-zero effect in the doped quantum wells composing the semiconductor hyperbolic metamaterial. Furthermore, different properties are observed for s and p polarizations, following the characteristics of the strong anisotropy of hyperbolic metamaterials.

Opioid Challenge Evaluation of Blockade by Extended-Release Naltrexone in Opioid-Abusing Adults: Dose-Effects and Time-Course

PubMed Central

Bigelow, George E.; Preston, Kenzie L.; Schmittner, John; Dong, Qunming; Gastfriend, David R.

2013-01-01

Background Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID:22079773

One-Dimensional Photonic Crystal Superprisms

NASA Technical Reports Server (NTRS)

Ting, David

2005-01-01

Theoretical calculations indicate that it should be possible for one-dimensional (1D) photonic crystals (see figure) to exhibit giant dispersions known as the superprism effect. Previously, three-dimensional (3D) photonic crystal superprisms have demonstrated strong wavelength dispersion - about 500 times that of conventional prisms and diffraction gratings. Unlike diffraction gratings, superprisms do not exhibit zero-order transmission or higher-order diffraction, thereby eliminating cross-talk problems. However, the fabrication of these 3D photonic crystals requires complex electron-beam substrate patterning and multilayer thin-film sputtering processes. The proposed 1D superprism is much simpler in structural complexity and, therefore, easier to design and fabricate. Like their 3D counterparts, the 1D superprisms can exhibit giant dispersions over small spectral bands that can be tailored by judicious structure design and tuned by varying incident beam direction. Potential applications include miniature gas-sensing devices.

Two novel bursting patterns in the Duffing system with multiple-frequency slow parametric excitations

NASA Astrophysics Data System (ADS)

Han, Xiujing; Zhang, Yi; Bi, Qinsheng; Kurths, Jürgen

2018-04-01

This paper aims to report two novel bursting patterns, the turnover-of-pitchfork-hysteresis-induced bursting and the compound pitchfork-hysteresis bursting, demonstrated for the Duffing system with multiple-frequency parametric excitations. Typically, a hysteresis behavior between the origin and non-zero equilibria of the fast subsystem can be observed due to delayed pitchfork bifurcation. Based on numerical analysis, we show that the stable equilibrium branches, related to the non-zero equilibria resulted from the pitchfork bifurcation, may become the ones with twists and turns. Then, the novel bursting pattern turnover-of-pitchfork-hysteresis-induced bursting is revealed accordingly. In particular, we show that additional pitchfork bifurcation points may appear in the fast subsystem under certain parameter conditions. This creates multiple delay-induced hysteresis behavior and helps us to reveal the other novel bursting pattern, the compound pitchfork-hysteresis bursting. Besides, effects of parameters on the bursting patterns are studied to explore the relation of these two novel bursting patterns.

Evaluation of the Geopotential value for the Local Vertical Datum of China using GRACE/GOCE GGMs and GPS/Leveling Data

NASA Astrophysics Data System (ADS)

He, Lin; Li, Jiancheng; Chu, Yonghai; Zhang, Tengxu

2017-04-01

National height reference systems have conventionally been linked to the coastal local mean sea level, observed at one tide gauge, such as the China national height datum 1985. Due to the effect of the local sea surface topography, the reference level surface of local datum is inconsistent with the global datum or other local datum. In order to unify or connect the local datum to the global height datum, it is necessary to obtain the zero-height geopotential value of local datum or the height offset with respect to the global datum. The GRACE and GOCE satellite mission are promising for purposes of unification of local vertical datums because they have brought a significant improvement in modeling of low-frequency or rather medium-frequency part of the Earth's static gravity field in the past ten years. The focus of this work is directed to the evaluation of most available Global Geopotential Models (GGMs) from GOCE and GRACE, both satellite only as well as combined ones. From the evaluation with the 649 GPS/Levelling benchmarks (BMs) in China, the GOCE/GRACE GGMs provide the accuracy at 42-52cm level, up to their max degree and order. The latest release 5 DIR, TIM GGMs improve the accuracies by 6-10cm compared to the release 1 models. The DIR_R1 is based on the fewer GOCE data performs equally well with the DIR_R4 and DIR_R5 model, this is attributed to the fact that during its development which used a priori information from EIGEN-51C. The zero-height geopotential value W0LVD for the China Local Vertical Datum (LVD) is 62636855.1606m2s-2 from the originally GOCE/GRACE GGMs. Taking into account the GPS/Levelling data contains the full spectral information, and the GOCE-only or GRACE-GOCE combined model are limited to the long wavelengths. To improve the accuracy of the GGMs, it is indispensable to account for the remaining signal above this maximum degree, known as the omission error of the GGM. The effect of GRACE/GOCE omission error is investigated by extending the models with the high-resolution gravity field model EGM2008. In China, the effect of the GRACE/GOCE GGMs omission error is at the decimeter level. The combined GGMs (up to 2160 degree and order) could provide an accuracy at 20cm level, which is better than that from EGM2008. Meanwhile, if an appropriate degree and order is chosen for the GOCE-only or GRACE-GOCE combined GGMs to connect with the EGM2008, the extended GGMs provide an accuracy at 16cm level. From the extended GGMs, the geopotential value W0LVD determined for the China local vertical datum is 62636853.4351 m2s-2 indicates a bias of about 2.5649 m2/s-2 compared to the conventional value of 62,636,856.0 m2s-2. This is support by National key research and development program No:2016YFB0501702. Keywords: Global Geopotential Models; GRACE; GOCE; GPS/Levelling; zero-height geopotential

Controlled release formulation of an anti-depression drug based on a L-phenylalanate-zinc layered hydroxide intercalation compound

NASA Astrophysics Data System (ADS)

Hashim, Norhayati; Sharif, Sharifah Norain Mohd; Isa, Illyas Md; Hamid, Shahidah Abdul; Hussein, Mohd Zobir; Bakar, Suriani Abu; Mamat, Mazidah

2017-06-01

The intercalation of L-phenylalanate (LP) into the interlayer gallery of zinc layered hydroxide (ZLH) has been successfully executed using a simple direct reaction method. The synthesised intercalation compound, zinc layered hydroxide-L-phenylalanate (ZLH-LP), was characterised using PXRD, FTIR, CHNS, ICP-OES, TGA/DTG, FESEM and TEM. The PXRD patterns of the intercalation compound demonstrate an intense and symmetrical peak, indicating a well-ordered crystalline layered structure. The appearance of an intercalation peak at a low angle of 2θ with a basal spacing of 16.3 Å, signifies the successful intercalation of the L-phenylalanate anion into the interlayer gallery of the host. The intercalation is also validated by FTIR spectroscopy and CHNS elemental analysis. Thermogravimetric analysis confirms that the ZLH-LP intercalation compound has higher thermal stability than the pristine L-phenylalanine. The observed percentage of L-phenylalanate accumulated release varies in each release media, with 84.5%, 79.8%, 63.8% and 61.8% release in phosphate buffer saline (PBS) solution at pH 4.8, deionised water, PBS solution at pH 7.4 and NaCl solution, respectively. The release behaviour of LP from its intercalation compounds in deionised water and PBS solution at pH 4.8 follows pseudo second order, whereas in NaCl solution and PBS solution at pH 7.4, it follows the parabolic diffusion model. This study shows that the synthesised ZLH-LP intercalation compound can be used for the formation of a new generation of materials for targeted drug release with controlled release properties.

Zero-Order Chemical Kinetics as a Context to Investigate Student Understanding of Catalysts and Half-Life

ERIC Educational Resources Information Center

Bain, Kinsey; Rodriguez, Jon-Marc G.; Towns, Marcy H.

2018-01-01

Zero-order systems provide an interesting opportunity for students to think about the underlying mechanism behind the physical phenomena being modeled. The work reported here is part of a larger study that seeks to characterize how students integrate chemistry and mathematics in the context of chemical kinetics. Thirty-six general chemistry…

Mass fractionation of noble gases in synthetic methane hydrate: Implications for naturally occurring gas hydrate dissociation

USGS Publications Warehouse

Hunt, Andrew G.; Stern, Laura; Pohlman, John W.; Ruppel, Carolyn; Moscati, Richard J.; Landis, Gary P.

2013-01-01

As a consequence of contemporary or longer term (since 15 ka) climate warming, gas hydrates in some settings may presently be dissociating and releasing methane and other gases to the ocean-atmosphere system. A key challenge in assessing the impact of dissociating gas hydrates on global atmospheric methane is the lack of a technique able to distinguish between methane recently released from gas hydrates and methane emitted from leaky thermogenic reservoirs, shallow sediments (some newly thawed), coal beds, and other sources. Carbon and deuterium stable isotopic fractionation during methane formation provides a first-order constraint on the processes (microbial or thermogenic) of methane generation. However, because gas hydrate formation and dissociation do not cause significant isotopic fractionation, a stable isotope-based hydrate-source determination is not possible. Here, we investigate patterns of mass-dependent noble gas fractionation within the gas hydrate lattice to fingerprint methane released from gas hydrates. Starting with synthetic gas hydrate formed under laboratory conditions, we document complex noble gas fractionation patterns in the gases liberated during dissociation and explore the effects of aging and storage (e.g., in liquid nitrogen), as well as sampling and preservation procedures. The laboratory results confirm a unique noble gas fractionation pattern for gas hydrates, one that shows promise in evaluating modern natural gas seeps for a signature associated with gas hydrate dissociation.

Chern Insulator Phase in a Lattice of an Organic Dirac Semimetal with Intracellular Potential and Magnetic Modulations

NASA Astrophysics Data System (ADS)

Osada, Toshihito

2017-12-01

We demonstrate that a Chern insulator can be realized on an actual two-dimensional lattice of an organic Dirac semimetal, α-(BEDT-TTF)2I3, by introducing potential and magnetic modulations in a unit cell. It is a topologically-nontrivial insulator that exhibits the quantum Hall effect even at zero magnetic field. We assume a pattern of site potential and staggered plaquette magnetic flux on the lattice to imitate the observed stripe charge ordering pattern. When magnetic modulation is sufficiently large, the system becomes a Chern insulator, where the Berry curvatures around two gapped Dirac cones have the same sign on each band, and one chiral edge state connects the conduction and valence bands at each crystal edge. The present model is an organic version of Haldane's model, which discusses the Chern insulator on a honeycomb lattice with second nearest neighbor couplings.

Study of a vibrating plate: comparison between experimental (ESPI) and analytical results

NASA Astrophysics Data System (ADS)

Romero, G.; Alvarez, L.; Alanís, E.; Nallim, L.; Grossi, R.

2003-07-01

Real-time electronic speckle pattern interferometry (ESPI) was used for tuning and visualization of natural frequencies of a trapezoidal plate. The plate was excited to resonant vibration by a sinusoidal acoustical source, which provided a continuous range of audio frequencies. Fringe patterns produced during the time-average recording of the vibrating plate—corresponding to several resonant frequencies—were registered. From these interferograms, calculations of vibrational amplitudes by means of zero-order Bessel functions were performed in some particular cases. The system was also studied analytically. The analytical approach developed is based on the Rayleigh-Ritz method and on the use of non-orthogonal right triangular co-ordinates. The deflection of the plate is approximated by a set of beam characteristic orthogonal polynomials generated by using the Gram-Schmidt procedure. A high degree of correlation between computational analysis and experimental results was observed.

Serial-data correlator/code translator

NASA Technical Reports Server (NTRS)

Morgan, L. E.

1977-01-01

System, consisting of sampling flip flop, memory (either RAM or ROM), and memory buffer, correlates sampled data with predetermined acceptance code patterns, translates acceptable code patterns to nonreturn-to-zero code, and identifies data dropouts.

Gaussian pre-filtering for uncertainty minimization in digital image correlation using numerically-designed speckle patterns

NASA Astrophysics Data System (ADS)

Mazzoleni, Paolo; Matta, Fabio; Zappa, Emanuele; Sutton, Michael A.; Cigada, Alfredo

2015-03-01

This paper discusses the effect of pre-processing image blurring on the uncertainty of two-dimensional digital image correlation (DIC) measurements for the specific case of numerically-designed speckle patterns having particles with well-defined and consistent shape, size and spacing. Such patterns are more suitable for large measurement surfaces on large-scale specimens than traditional spray-painted random patterns without well-defined particles. The methodology consists of numerical simulations where Gaussian digital filters with varying standard deviation are applied to a reference speckle pattern. To simplify the pattern application process for large areas and increase contrast to reduce measurement uncertainty, the speckle shape, mean size and on-center spacing were selected to be representative of numerically-designed patterns that can be applied on large surfaces through different techniques (e.g., spray-painting through stencils). Such 'designer patterns' are characterized by well-defined regions of non-zero frequency content and non-zero peaks, and are fundamentally different from typical spray-painted patterns whose frequency content exhibits near-zero peaks. The effect of blurring filters is examined for constant, linear, quadratic and cubic displacement fields. Maximum strains between ±250 and ±20,000 με are simulated, thus covering a relevant range for structural materials subjected to service and ultimate stresses. The robustness of the simulation procedure is verified experimentally using a physical speckle pattern subjected to constant displacements. The stability of the relation between standard deviation of the Gaussian filter and measurement uncertainty is assessed for linear displacement fields at varying image noise levels, subset size, and frequency content of the speckle pattern. It is shown that bias error as well as measurement uncertainty are minimized through Gaussian pre-filtering. This finding does not apply to typical spray-painted patterns without well-defined particles, for which image blurring is only beneficial in reducing bias errors.

Nematic order on the surface of a three-dimensional topological insulator

NASA Astrophysics Data System (ADS)

Lundgren, Rex; Yerzhakov, Hennadii; Maciejko, Joseph

2017-12-01

We study the spontaneous breaking of rotational symmetry in the helical surface state of three-dimensional topological insulators due to strong electron-electron interactions, focusing on time-reversal invariant nematic order. Owing to the strongly spin-orbit coupled nature of the surface state, the nematic order parameter is linear in the electron momentum and necessarily involves the electron spin, in contrast with spin-degenerate nematic Fermi liquids. For a chemical potential at the Dirac point (zero doping), we find a first-order phase transition at zero temperature between isotropic and nematic Dirac semimetals. This extends to a thermal phase transition that changes from first to second order at a finite-temperature tricritical point. At finite doping, we find a transition between isotropic and nematic helical Fermi liquids that is second order even at zero temperature. Focusing on finite doping, we discuss various observable consequences of nematic order, such as anisotropies in transport and the spin susceptibility, the partial breakdown of spin-momentum locking, collective modes and induced spin fluctuations, and non-Fermi-liquid behavior at the quantum critical point and in the nematic phase.

Path integral Monte Carlo determination of the fourth-order virial coefficient for unitary two-component Fermi gas with zero-range interactions

NASA Astrophysics Data System (ADS)

Yan, Yangqian; Blume, D.

2016-05-01

The unitary equal-mass Fermi gas with zero-range interactions constitutes a paradigmatic model system that is relevant to atomic, condensed matter, nuclear, particle, and astro physics. This work determines the fourth-order virial coefficient b4 of such a strongly-interacting Fermi gas using a customized ab inito path integral Monte Carlo (PIMC) algorithm. In contrast to earlier theoretical results, which disagreed on the sign and magnitude of b4, our b4 agrees with the experimentally determined value, thereby resolving an ongoing literature debate. Utilizing a trap regulator, our PIMC approach determines the fourth-order virial coefficient by directly sampling the partition function. An on-the-fly anti-symmetrization avoids the Thomas collapse and, combined with the use of the exact two-body zero-range propagator, establishes an efficient general means to treat small Fermi systems with zero-range interactions. We gratefully acknowledge support by the NSF.

Path-Integral Monte Carlo Determination of the Fourth-Order Virial Coefficient for a Unitary Two-Component Fermi Gas with Zero-Range Interactions.

PubMed

Yan, Yangqian; Blume, D

2016-06-10

The unitary equal-mass Fermi gas with zero-range interactions constitutes a paradigmatic model system that is relevant to atomic, condensed matter, nuclear, particle, and astrophysics. This work determines the fourth-order virial coefficient b_{4} of such a strongly interacting Fermi gas using a customized ab initio path-integral Monte Carlo (PIMC) algorithm. In contrast to earlier theoretical results, which disagreed on the sign and magnitude of b_{4}, our b_{4} agrees within error bars with the experimentally determined value, thereby resolving an ongoing literature debate. Utilizing a trap regulator, our PIMC approach determines the fourth-order virial coefficient by directly sampling the partition function. An on-the-fly antisymmetrization avoids the Thomas collapse and, combined with the use of the exact two-body zero-range propagator, establishes an efficient general means to treat small Fermi systems with zero-range interactions.

78 FR 61416 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... zero or the lowest Minimum Trading Increment or (ii) the Expanded Quote Range has been calculated as zero. The proposal codifies existing functionality during the Exchange's Opening Process. Specifically... either zero or the lowest Minimum Trading Increment and market order sell interest has a quantity greater...

40 CFR 89.313 - Initial calibration of analyzers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the HFID analyzer shall be optimized in order to meet the specifications in § 89.319(b)(2). (c) Zero... analyzers shall be set at zero. (2) Introduce the appropriate calibration gases to the analyzers and the values recorded. The same gas flow rates shall be used as when sampling exhaust. (d) Rechecking of zero...

40 CFR 89.313 - Initial calibration of analyzers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the HFID analyzer shall be optimized in order to meet the specifications in § 89.319(b)(2). (c) Zero... analyzers shall be set at zero. (2) Introduce the appropriate calibration gases to the analyzers and the values recorded. The same gas flow rates shall be used as when sampling exhaust. (d) Rechecking of zero...

40 CFR 89.313 - Initial calibration of analyzers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the HFID analyzer shall be optimized in order to meet the specifications in § 89.319(b)(2). (c) Zero... analyzers shall be set at zero. (2) Introduce the appropriate calibration gases to the analyzers and the values recorded. The same gas flow rates shall be used as when sampling exhaust. (d) Rechecking of zero...

40 CFR 89.313 - Initial calibration of analyzers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the HFID analyzer shall be optimized in order to meet the specifications in § 89.319(b)(2). (c) Zero... analyzers shall be set at zero. (2) Introduce the appropriate calibration gases to the analyzers and the values recorded. The same gas flow rates shall be used as when sampling exhaust. (d) Rechecking of zero...

40 CFR 89.313 - Initial calibration of analyzers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the HFID analyzer shall be optimized in order to meet the specifications in § 89.319(b)(2). (c) Zero... analyzers shall be set at zero. (2) Introduce the appropriate calibration gases to the analyzers and the values recorded. The same gas flow rates shall be used as when sampling exhaust. (d) Rechecking of zero...

Texture one zero Dirac neutrino mass matrix with vanishing determinant or trace condition

NASA Astrophysics Data System (ADS)

Singh, Madan

2018-06-01

In the light of non-zero and relatively large value of rector mixing angle (θ13), we have performed a detailed analysis of texture one zero neutrino mass matrix Mν in the scenario of vanishing determinant/trace conditions, assuming the Dirac nature of neutrinos. In both the scenarios, normal mass ordering is ruled out for all the six possibilities of Mν, however for inverted mass ordering, only two are found to be viable with the current neutrino oscillation data at 3σ confidence level. Numerical and some approximate analytical results are presented.

Three-dimensional charge density wave order in YBa 2Cu 3O 6.67 at high magnetic fields

DOE PAGES

Gerber, S.; Jang, H.; Nojiri, H.; ...

2015-11-20

In this study, charge density wave (CDW) correlations have recently been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from that measured by x-ray scattering at zero and low fields. Here we combine a pulsed magnet with an x-ray free electron laser to characterize the CDW in YBa 2Cu 3O 6.67 via x-ray scattering in fields up to 28 Tesla. While the zero-field CDW order, which develops below T ~ 150 K, is essentially two-dimensional, at lower temperature and beyond 15 Tesla, another three-dimensionally ordered CDW emerges. Themore » field-induced CDW onsets around the zero-field superconducting transition temperature, yet the incommensurate in-plane ordering vector is field-independent. This implies that the two forms of CDW and high-temperature superconductivity are intimately linked.« less

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.

Near-zero thermal expansion in magnetically ordered state in dysprosium at high pressures and low temperatures

NASA Astrophysics Data System (ADS)

Hope, Kevin M.; Samudrala, Gopi K.; Vohra, Yogesh K.

2017-01-01

The atomic volume of rare earth metal dysprosium (Dy) has been measured up to high pressures of 35 GPa and low temperatures between 200 and 7 K in a diamond anvil cell using angle dispersive X-ray diffraction at a synchrotron source. The hexagonal close-packed (hcp), alpha-Samarium (α-Sm), and double hexagonal close-packed (dhcp) phases are observed to be stable in Dy under high-pressure and low-temperature conditions achieved in our experiments. Dy is known to undergo magnetic ordering below 176 K at ambient pressure with magnetic ordering Néel temperature (TN) that changes rapidly with increasing pressure. Our experimental measurement shows that Dy has near-zero thermal expansion in the magnetically ordered state and normal thermal expansion in the paramagnetic state for all the three known high pressure phases (hcp, α-Sm, and dhcp) to 35 GPa. This near-zero thermal expansion behavior in Dy is observed below the magnetic ordering temperature TN at all pressures up to 35 GPa.

Accumulation and distribution characteristics of biomass and nitrogen in bitter gourd (Momordica charantia L.) under different fertilization strategies.

PubMed

Zhang, Baige; Li, Mingzhu; Li, Qiang; Cao, Jian; Zhang, Changyuan; Zhang, Fusuo; Song, Zhao; Chen, Xinping

2018-05-01

The elemental uptake and allocation patterns of crops create insight for nutrient management. Two-year field experiments were conducted to determine the growth and nitrogen (N) uptake patterns of bitter gourd and to evaluate different N management strategies. Two N practices during the nursery stage, namely the conventional fertilizer method (Scon) and the controlled-release fertilizer management method (Scrf), combined with three N management strategies after transplanting, namely zero N fertilizer application (Nno), the conventional strategy (Ncon) and the systematic N management strategy (Nopt), were assessed. Averaged over two years, the Scrf-Nopt treatment performed best, producing 33.1 t ha -1 fruit yield with 310 kg N ha -1 , indicating that the yield was 22.6% greater by using 18.8% less fertilizer N than in the Scon-Ncon treatment. The Scrf-Nopt treatment facilitated plant growth by accumulating 20.0% more total dry weight and prioritized its allocation to productive organs (57.2%), while the Scon-Ncon strategy was biased toward leaves (56.3%) over fruits (43.8%). Nitrogen uptake and distribution closely followed the pattern of biomass. The Scrf-Nopt fertilization strategy coordinated the important role that N plays in total accumulation and well proportion of biomass and N in bitter gourd developmental processes. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Diurnal Pattern of Leaf, Flower and Fruit Specific Ambient Volatiles above an Oil Palm Plantation in Pará State, Brazil

DOE PAGES

Jardine, Kolby J.; Gimenez, Bruno O.; Araujo, Alessandro C.; ...

2016-01-01

Oil palm plantations are rapidly expanding in the tropics because of insatiable global demand for fruit oil to be used in food, biofuels and cosmetics. Here we show that three tissue-specific volatiles can be quantified in ambient air above an African-American hybrid oil palm plantation in Brazil and linked photosynthesis (isoprene), floral scent (estragole), and for the first time, fruit oil processing (6-methyl-5-hepten-2-one, MHO). Plant enclosure techniques verified their tissue specific emission sources with ambient concentrations displaying distinct diurnal patterns above the canopy. Isoprene concentrations were near zero at night, but dramatically increased during the day while estragole showed elevatedmore » concentrations at night suggesting a light-independent, temperature-driven emission pattern from flowers. MHO also showed elevated concentrations at night and both estragole and MHO increased during the day. Our observations demonstrate that the African-American oil palm hybrid is strong isoprene emitter and suggest that MHO is a specific oxidation product of lycopene released during the industrial processing of palm oil. This study highlights the potential value of quantifying volatile oil palm signals in the atmosphere as a novel, non-invasive method to better understand biological functioning and its interactions with the environment including carbon assimilation, floral-insect interactions, and fruit oil production/processing.« less

Diurnal Pattern of Leaf, Flower and Fruit Specific Ambient Volatiles above an Oil Palm Plantation in Pará State, Brazil

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

Jardine, Kolby J.; Gimenez, Bruno O.; Araujo, Alessandro C.

Oil palm plantations are rapidly expanding in the tropics because of insatiable global demand for fruit oil to be used in food, biofuels and cosmetics. Here we show that three tissue-specific volatiles can be quantified in ambient air above an African-American hybrid oil palm plantation in Brazil and linked photosynthesis (isoprene), floral scent (estragole), and for the first time, fruit oil processing (6-methyl-5-hepten-2-one, MHO). Plant enclosure techniques verified their tissue specific emission sources with ambient concentrations displaying distinct diurnal patterns above the canopy. Isoprene concentrations were near zero at night, but dramatically increased during the day while estragole showed elevatedmore » concentrations at night suggesting a light-independent, temperature-driven emission pattern from flowers. MHO also showed elevated concentrations at night and both estragole and MHO increased during the day. Our observations demonstrate that the African-American oil palm hybrid is strong isoprene emitter and suggest that MHO is a specific oxidation product of lycopene released during the industrial processing of palm oil. This study highlights the potential value of quantifying volatile oil palm signals in the atmosphere as a novel, non-invasive method to better understand biological functioning and its interactions with the environment including carbon assimilation, floral-insect interactions, and fruit oil production/processing.« less

Zero-order controlled release of BMP2-derived peptide P24 from the chitosan scaffold by chemical grafting modification technique for promotion of osteogenesis in vitro and enhancement of bone repair in vivo.

PubMed

Chen, Yan; Liu, Xujie; Liu, Rui; Gong, Yong; Wang, Mingbo; Huang, Qianli; Feng, Qingling; Yu, Bo

2017-01-01

Combination of tissue-engineered bone scaffolds with cell-adhesive, osteoconductive, or osteoinductive biomolecules is a critical strategy to improve their properties that significantly influence cellular behaviors, such as adhesion, proliferation, and differentiation, which is beneficial for critical-sized bone defects repairing. However, the traditional surface modification techniques, such as physical adsorption, coating, and plasma treatment, et al, have great limitations for immobilization of bioactive molecules due to undesirable controlled delivery performance or overly complex multistep procedures. In this study, we functionalized the chitosan/hydroxyapatite (CS/HA) biomimetic composite scaffold for controlled delivery of BMP2-derived peptide (P24) by the chemical grafting modification technique: firstly, P24 was conjugated with a thiolated chitosan, chitosan-4-thiobutylamidine (CS-TBA); secondly, the resultant CS-P24 was then combined with HA to prepare CS-P24/HA scaffolds. The effect of CS-P24/HA scaffolds on bone regeneration was evaluated, along with the underlying biological mechanisms responsible in vitro and in vivo . In vitro , the controlled and sustained release of bioactive P24 could last up to 90 days, furthermore, the release profiles of CS-5%P24/HA and CS-10%P24/HA were linear and could be fitted according to zero-order kinetic model (R 2 =0.9929; R 2 =0.9757); P24 on the scaffold significantly promoted cell adhesion, proliferation, osteodifferentiation, and mineralization with synergistic effects. Bone marrow stromal cells (BMSCs) revealed spindle-shaped surface morphology, indicating the CS-P24/HA scaffolds supported cell adhesion and possessed a high proliferation rate that varied according to the P24 concentration levels. Furthermore, mRNA levels for OCN, Runx2, and collagen I were significantly up-regulated on CS-P24/HA scaffolds compared with cells grown on CS/HA scaffolds in vitro ( p < 0.05). Similarly, the BMSCs exhibited a higher ALP expression and calcium deposition level on CS-P24/HA scaffolds compared with CS/HA scaffolds ( p < 0.05). In vivo , osteoinductive studies revealed a significantly higher ectopic osteogenesis level of CS-10%P24/HA scaffolds in rat dorsal muscle pockets compared with that of CS/HA scaffolds. Finally, CS-P24/HA scaffolds showed superior performance in the reconstruction of rat calvarial bone defects. This novel CS-P24/HA scaffold is deemed a strong potential candidate for the repair of bone defects in human bone tissue engineering.

Zero-order controlled release of BMP2-derived peptide P24 from the chitosan scaffold by chemical grafting modification technique for promotion of osteogenesis in vitro and enhancement of bone repair in vivo

PubMed Central

Chen, Yan; Liu, Xujie; Liu, Rui; Gong, Yong; Wang, Mingbo; Huang, Qianli; Feng, Qingling; Yu, Bo

2017-01-01

Combination of tissue-engineered bone scaffolds with cell-adhesive, osteoconductive, or osteoinductive biomolecules is a critical strategy to improve their properties that significantly influence cellular behaviors, such as adhesion, proliferation, and differentiation, which is beneficial for critical-sized bone defects repairing. However, the traditional surface modification techniques, such as physical adsorption, coating, and plasma treatment, et al, have great limitations for immobilization of bioactive molecules due to undesirable controlled delivery performance or overly complex multistep procedures. In this study, we functionalized the chitosan/hydroxyapatite (CS/HA) biomimetic composite scaffold for controlled delivery of BMP2-derived peptide (P24) by the chemical grafting modification technique: firstly, P24 was conjugated with a thiolated chitosan, chitosan-4-thiobutylamidine (CS-TBA); secondly, the resultant CS-P24 was then combined with HA to prepare CS-P24/HA scaffolds. The effect of CS-P24/HA scaffolds on bone regeneration was evaluated, along with the underlying biological mechanisms responsible in vitro and in vivo. In vitro, the controlled and sustained release of bioactive P24 could last up to 90 days, furthermore, the release profiles of CS-5%P24/HA and CS-10%P24/HA were linear and could be fitted according to zero-order kinetic model (R2=0.9929; R2=0.9757); P24 on the scaffold significantly promoted cell adhesion, proliferation, osteodifferentiation, and mineralization with synergistic effects. Bone marrow stromal cells (BMSCs) revealed spindle-shaped surface morphology, indicating the CS-P24/HA scaffolds supported cell adhesion and possessed a high proliferation rate that varied according to the P24 concentration levels. Furthermore, mRNA levels for OCN, Runx2, and collagen I were significantly up-regulated on CS-P24/HA scaffolds compared with cells grown on CS/HA scaffolds in vitro (p < 0.05). Similarly, the BMSCs exhibited a higher ALP expression and calcium deposition level on CS-P24/HA scaffolds compared with CS/HA scaffolds (p < 0.05). In vivo, osteoinductive studies revealed a significantly higher ectopic osteogenesis level of CS-10%P24/HA scaffolds in rat dorsal muscle pockets compared with that of CS/HA scaffolds. Finally, CS-P24/HA scaffolds showed superior performance in the reconstruction of rat calvarial bone defects. This novel CS-P24/HA scaffold is deemed a strong potential candidate for the repair of bone defects in human bone tissue engineering. PMID:28435449

Balancing specificity, sensitivity, and speed of ligand discrimination by zero-order ultraspecificity

NASA Astrophysics Data System (ADS)

Kajita, Masashi K.; Aihara, Kazuyuki; Kobayashi, Tetsuya J.

2017-07-01

Specific interactions between receptors and their target ligands in the presence of nontarget ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and nontarget ligands, cells have to increase specificity to the target ligands by amplifying the small differences in affinity among ligands. In addition, sensitivity to the ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition. In this work we propose a mechanism for nonlinear specificity amplification (ultraspecificity) based on zero-order saturating reactions, which was originally proposed to explain nonlinear sensitivity amplification (ultrasensitivity) to the ligand concentration. In contrast to the previously proposed proofreading mechanisms that amplify the specificity by a multistep reaction, our model can produce an optimal balance of specificity, sensitivity, and quick discrimination. Furthermore, we show that a model for insensitivity to a large number of nontarget ligands can be naturally derived from a model with the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may provide an alternative way to understand ligand discrimination from the viewpoint of nonlinear properties in biochemical reactions.

Marangoni bubble motion in zero gravity. [Lewis zero gravity drop tower

NASA Technical Reports Server (NTRS)

Thompson, R. L.; Dewitt, K. J.

1979-01-01

It was shown experimentally that the Marangoni phenomenon is a primary mechanism for the movement of a gas bubble in a nonisothermal liquid in a low gravity environment. A mathematical model consisting of the Navier-Stokes and thermal energy equations, together with the appropriate boundary conditions for both media, is presented. Parameter perturbation theory is used to solve this boundary value problem; the expansion parameter is the Marangoni number. The zeroth, first, and second order approximations for the velocity, temperature and pressure distributions in the liquid and in the bubble, and the deformation and terminal velocity of the bubble are determined. Experimental zero gravity data for a nitrogen bubble in ethylene glycol, ethanol, and silicone oil subjected to a linear temperature gradient were obtained using the NASA Lewis zero gravity drop tower. Comparison of the zeroth order analytical results for the bubble terminal velocity showed good agreement with the experimental measurements. The first and second order solutions for the bubble deformation and bubble terminal velocity are valid for liquids having Prandtl numbers on the order of one, but there is a lack of appropriate data to test the theory fully.

Spatial eigenmodes and synchronous oscillation: co-incidence detection in simulated cerebral cortex.

PubMed

Chapman, Clare L; Wright, James J; Bourke, Paul D

2002-07-01

Zero-lag synchronisation arises between points on the cerebral cortex receiving concurrent independent inputs; an observation generally ascribed to nonlinear mechanisms. Using simulations of cerebral cortex and Principal Component Analysis (PCA) we show patterns of zero-lag synchronisation (associated with empirically realistic spectral content) can arise from both linear and nonlinear mechanisms. For low levels of activation, we show the synchronous field is described by the eigenmodes of the resultant damped wave activity. The first and second spatial eigenmodes (which capture most of the signal variance) arise from the even and odd components of the independent input signals. The pattern of zero-lag synchronisation can be accounted for by the relative dominance of the first mode over the second, in the near-field of the inputs. The simulated cortical surface can act as a few millisecond response coincidence detector for concurrent, but uncorrelated, inputs. As cortical activation levels are increased, local damped oscillations in the gamma band undergo a transition to highly nonlinear undamped activity with 40 Hz dominant frequency. This is associated with "locking" between active sites and spatially segregated phase patterns. The damped wave synchronisation and the locked nonlinear oscillations may combine to permit fast representation of multiple patterns of activity within the same field of neurons.

Role of cellulose ether polymers on ibuprofen release from matrix tablets.

PubMed

Vueba, M L; Batista de Carvalho, L A E; Veiga, F; Sousa, J J; Pina, Maria Eugénia

2005-08-01

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

Formulation and evaluation of bucco-adhesive tablets of sumatriptan succinate

PubMed Central

Prasanna, R Indira; Anitha, P; Chetty, C Madhusudhana

2011-01-01

Background: A novel aspiration in treatment of migraine, to provide greater therapeutic effect, overcome the side effects by complex therapeutic regimen and to improve patient compliance upon administering bucco-adhesive tablet formulations of sumatriptan succinate which have not been tested literally. Materials and Methods: This study was designed to develop a bucco-adhesive tablet containing sumatriptan succinate using blends of different bio-adhesive polymeric combinations such as hydroxy propyl methyl cellulose K4M, sodium carboxy methyl cellulose, and Carbopol 934P with a backing layer of ethyl cellulose by a direct compression technique. Tablets were subjected to physico-chemical parameters, swelling index, surface pH, ex vivo bioadhesive force, in vitro drug release, ex vivo drug permeation, and stability in saliva. Results: Good results were obtained in all the evaluated parameters. The drug release of all formulation follows zero-order kinetics by a diffusion mechanism type. Stability studies in human saliva, ex vivo buccal permeation studies by using sheep and porcine buccal mucosa were carried out for the optimized formulation (S4 CP:HPMC 3:1). Conclusion: The developed buccal drug delivery system containing sumatriptan succinate might be the alternative routes available to bypass the first pass metabolism and might be a milestone in the therapy of migraine and among all formulations S4 shows good controlled release results correlated with ex vivo permeation studies. PMID:23071941

Development and evaluation of emulsion-liposome blends for resveratrol delivery.

PubMed

Hung, Chi-Feng; Chen, Jan-Kan; Liao, Mei-Hui; Lo, Huey-Ming; Fang, Jia-You

2006-01-01

Nano- and submicron-sized vesicles are beneficial for the controlled delivery of drugs. Resveratrol, the main active polyphenol in red wine, was incorporated into various combinations of emulsions and liposomes to examine its physicochemical characteristics and cardiovascular protection. The blends of emulsion-liposome were composed of coconut oil, soybean lecithin, glycerol formal, and non-ionic surfactants. Multiple systems were assessed by evaluating the droplet size, surface charge, drug encapsulation, release rate, and stability. The vesicle diameter of the systems ranged from 114 to 195 nm. The liposomal vesicles in the systems had smaller diameters (of 43 approximately 56 nm) (F6 and F7). Drug encapsulation of approximately 70% were achieved by the vesicles. The inclusion of resveratrol in these systems retarded the drug release in both the presence and absence of plasma in vitro. The emulsion-liposome blends which incorporated Brij 98 (F5) exhibited the slowest release at zero-order for resveratrol delivery. Treatment using resveratrol in the blended formulations dramatically inhibited vascular intimal thickening, which was tested in an experimental model in which endothelial injury was produced in normal rat carotid arteries. Intraperitoneal injection of the multiple systems was associated with no or negligible liver and kidney toxicity. We concluded that encapsulation by the emulsion-liposome blends is a potent way to enhance the preventative and therapeutic benefits of resveratrol.

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

Gerber, S.; Jang, H.; Nojiri, H.

Charge density wave (CDW) correlations have been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from that measured by x-ray scattering at zero and low fields. Here we combine a pulsed magnet with an x-ray free electron laser to characterize the CDW in YBa2Cu3O6.67 via x-ray scattering in fields up to 28 Tesla. While the zero-field CDW order, which develops below T ~ 150 K, is essentially two-dimensional, at lower temperature and beyond 15 Tesla, another three-dimensionally ordered CDW emerges. The field-induced CDW onsets around the zero-field superconductingmore » transition temperature, yet the incommensurate inplane ordering vector is field-independent. This implies that the two forms of CDW and hightemperature superconductivity are intimately linked.« less

Polarization errors associated with birefringent waveplates

NASA Technical Reports Server (NTRS)

West, Edward A.; Smith, Matthew H.

1995-01-01

Although zero-order quartz waveplates are widely used in instrumentation that needs good temperature and field-of-view characteristics, the residual errors associated with these devices can be very important in high-resolution polarimetry measurements. How the field-of-view characteristics are affected by retardation errors and the misalignment of optic axes in a double-crystal waveplate is discussed. The retardation measurements made on zero-order quartz and single-order 'achromatic' waveplates and how the misalignment errors affect those measurements are discussed.

Electrospun formulations of bevacizumab for sustained release in the eye.

PubMed

Angkawinitwong, Ukrit; Awwad, Sahar; Khaw, Peng T; Brocchini, Steve; Williams, Gareth R

2017-12-01

Medicines based on vascular endothelial growth factor (VEGF) neutralising antibodies such as bevacizumab have revolutionized the treatment of age related macular degeneration (AMD), a common blinding disease, and have great potential in preventing scarring after surgery or accelerating the healing of corneal injuries. However, at present frequent invasive injections are required to deliver these antibodies. Such administration is uncomfortable for patients and expensive for health service providers. Much effort is thus focused on developing dosage forms that can be administered less frequently. Here we use electrospinning to prepare a solid form of bevacizumab designed for prolonged release while maintaining antibody stability. Electrospun fibers were prepared with bevacizumab encapsulated in the core, surrounded by a poly-ε-caprolactone sheath. The fibers were generated using aqueous bevacizumab solutions buffered at two different pH values: 6.2 (the pH of the commercial product; F beva ) and 8.3 (the isoelectric point of bevacizumab; F bevaP ). The fibers had smooth and cylindrical morphologies, with diameters of ca. 500nm. Both sets of bevacizumab loaded fibers gave sustained release profiles in an in vitro model of the subconjunctival space of the eye. F beva displayed first order kinetics with t 1/2 of 11.4±4.4 days, while F bevaP comprises a zero-order reservoir type release system with t 1/2 of 52.9±14.8 days. Both SDS-PAGE and surface plasmon resonance demonstrate that the bevacizumab in F bevaP did not undergo degradation during fiber fabrication or release. In contrast, the antibody released from F beva had degraded, and failed to bind to VEGF. Our results demonstrate that pH control is crucial to maintain antibody stability during the fabrication of core/shell fibers and ensure release of functional protein. Bevacizumab is a potent protein drug which is highly effective in the treatment of degenerative conditions in the eye. To be effective, frequent injections into the eye are required, which is deeply unpleasant for patients and expensive for healthcare providers. Alternative methods of administration are thus highly sought after. In our work, we use the electrospinning technique to prepare fiber-based formulations loaded with bevacizumab. By careful control of the experimental parameters we are able to stabilize the protein during processing and ensure a constant rate of release over more than two months in vitro. These fibers could thus be used to reduce the frequency of dosing required, reducing cost and improving patient outcomes. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

77 FR 64571 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-22

... Change To Amend its Rules To Clarify the Handling of Zero Displayed Reserve Orders During Crossed Markets...) clarify that the Exchange's trading system (the ``System'' \\3\\) will not execute a Zero Display Reserve.... Purpose The Exchange is proposing to amend its rules to clarify that the System will not execute Zero...

Is it worth hyperaccumulating Ni on non-serpentine soils? Decomposition dynamics of mixed-species litters containing hyperaccumulated Ni across serpentine and non-serpentine environments.

PubMed

Adamidis, George C; Kazakou, Elena; Aloupi, Maria; Dimitrakopoulos, Panayiotis G

2016-06-01

Nickel (Ni)-hyperaccumulating species produce high-Ni litters and may potentially influence important ecosystem processes such as decomposition. Although litters resembling the natural community conditions are essential in order to predict decomposition dynamics, decomposition of mixed-species litters containing hyperaccumulated Ni has never been studied. This study aims to test the effect of different litter mixtures containing hyperaccumulated Ni on decomposition and Ni release across serpentine and non-serpentine soils. Three different litter mixtures were prepared based on the relative abundance of the dominant species in three serpentine soils in the island of Lesbos, Greece where the Ni-hyperaccumulator Alyssum lesbiacum is present. Each litter mixture decomposed on its original serpentine habitat and on an adjacent non-serpentine habitat, in order to investigate whether the decomposition rates differ across the contrasted soils. In order to make comparisons across litter mixtures and to investigate whether additive or non-additive patterns of mass loss occur, a control non-serpentine site was used. Mass loss and Ni release were measured after 90, 180 and 270 d of field exposure. The decomposition rates and Ni release had higher values on serpentine soils after all periods of field exposure. The recorded rapid release of hyperaccumulated Ni is positively related to the initial litter Ni concentration. No differences were found in the decomposition of the three different litter mixtures at the control non-serpentine site, while their patterns of mass loss were additive. Our results: (1) demonstrate the rapid decomposition of litters containing hyperaccumulated Ni on serpentine soils, indicating the presence of metal-tolerant decomposers; and (2) imply the selective decomposition of low-Ni parts of litters by the decomposers on non-serpentine soils. This study provides support for the elemental allelopathy hypothesis of hyperaccumulation, presenting the potential selective advantages acquired by metal-hyperaccumulating plants through litter decomposition on serpentine soils. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

More about unphysical zeroes in quark mass matrices

NASA Astrophysics Data System (ADS)

Emmanuel-Costa, David; González Felipe, Ricardo

2017-01-01

We look for all weak bases that lead to texture zeroes in the quark mass matrices and contain a minimal number of parameters in the framework of the standard model. Since there are ten physical observables, namely, six nonvanishing quark masses, three mixing angles and one CP phase, the maximum number of texture zeroes in both quark sectors is altogether nine. The nine zero entries can only be distributed between the up- and down-quark sectors in matrix pairs with six and three texture zeroes or five and four texture zeroes. In the weak basis where a quark mass matrix is nonsingular and has six zeroes in one sector, we find that there are 54 matrices with three zeroes in the other sector, obtainable through right-handed weak basis transformations. It is also found that all pairs composed of a nonsingular matrix with five zeroes and a nonsingular and nondecoupled matrix with four zeroes simply correspond to a weak basis choice. Without any further assumptions, none of these pairs of up- and down-quark mass matrices has physical content. It is shown that all non-weak-basis pairs of quark mass matrices that contain nine zeroes are not compatible with current experimental data. The particular case of the so-called nearest-neighbour-interaction pattern is also discussed.

New observational constraints on f ( R ) gravity from cosmic chronometers

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

Nunes, Rafael C.; Pan, Supriya; Saridakis, Emmanuel N.

We use the recently released cosmic chronometer data and the latest measured value of the local Hubble parameter, combined with the latest joint light curves of Supernovae Type Ia, and Baryon Acoustic Oscillation distance measurements, in order to impose constraints on the viable and most used f ( R ) gravity models. We consider four f ( R ) models, namely the Hu-Sawicki, the Starobinsky, the Tsujikawa, and the exponential one, and we parametrize them introducing a distortion parameter b that quantifies the deviation from ΛCDM cosmology. Our analysis reveals that a small but non-zero deviation from ΛCDM cosmology ismore » slightly favored, with the corresponding fittings exhibiting very efficient AIC and BIC Information Criteria values. Clearly, f ( R ) gravity is consistent with observations, and it can serve as a candidate for modified gravity.« less

Optical Pattern Formation in Spatially Bunched Atoms: A Self-Consistent Model and Experiment

NASA Astrophysics Data System (ADS)

Schmittberger, Bonnie L.; Gauthier, Daniel J.

2014-05-01

The nonlinear optics and optomechanical physics communities use different theoretical models to describe how optical fields interact with a sample of atoms. There does not yet exist a model that is valid for finite atomic temperatures but that also produces the zero temperature results that are generally assumed in optomechanical systems. We present a self-consistent model that is valid for all atomic temperatures and accounts for the back-action of the atoms on the optical fields. Our model provides new insights into the competing effects of the bunching-induced nonlinearity and the saturable nonlinearity. We show that it is crucial to keep the fifth and seventh-order nonlinearities that arise when there exists atomic bunching, even at very low optical field intensities. We go on to apply this model to the results of our experimental system where we observe spontaneous, multimode, transverse optical pattern formation at ultra-low light levels. We show that our model accurately predicts our experimentally observed threshold for optical pattern formation, which is the lowest threshold ever reported for pattern formation. We gratefully acknowledge the financial support of the NSF through Grant #PHY-1206040.

Characterizing featureless Mott insulating state by quasiparticle interference: A dynamical mean field theory view

NASA Astrophysics Data System (ADS)

Mukherjee, Shantanu; Lee, Wei-Cheng

2015-12-01

The quasiparticle interferences (QPIs) of the featureless Mott insulators are investigated by a T -matrix formalism implemented with the dynamical mean field theory (T -DMFT). In the Mott insulating state, due to the singularity at zero frequency in the real part of the electron self-energy [Re Σ (ω )˜η /ω ] predicted by DMFT, where η can be considered as the "order parameter" for the Mott insulating state, QPIs are completely washed out at small bias voltages. However, a further analysis shows that Re Σ (ω ) serves as an energy-dependent chemical potential shift. As a result, the effective bias voltage seen by the system is e V'=e V -Re Σ (e V ) , which leads to a critical bias voltage e Vc˜√{η } satisfying e V'=0 if and only if η is nonzero. Consequently, the same QPI patterns produced by the noninteracting Fermi surfaces appear at this critical bias voltage e Vc in the Mott insulating state. We propose that this reentry of noninteracting QPI patterns at e Vc could serve as an experimental signature of the Mott insulating state, and the order parameter can be experimentally measured as η ˜(eVc) 2 .

Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

PubMed Central

O'Brien, P J

1986-01-01

This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

Education or Incarceration: Zero Tolerance Policies and the School to Prison Pipeline

ERIC Educational Resources Information Center

Heitzeg, Nancy A.

2009-01-01

In the past decade, there has been a growing convergence between schools and legal systems. The school to prison pipeline refers to this growing pattern of tracking students out of educational institutions, primarily via "zero tolerance" policies, and, directly and/or indirectly, into the juvenile and adult criminal justice systems. The school to…

Zero-Base Curriculum Revision: A Concept Worth Trying.

ERIC Educational Resources Information Center

Miller, William C.

1981-01-01

Argues for a "zero-base" revision of school curricula in order to weed out poorly functioning components. Outlines procedures for carrying out such a revision at both the district and building levels. (WD)

Anomalous nonlinear absorption in epsilon-near-zero materials: optical limiting and all-optical control.

PubMed

Vincenti, M A; de Ceglia, D; Scalora, Michael

2016-08-01

We investigate nonlinear absorption in films of epsilon-near-zero materials. The combination of large local electric fields at the fundamental frequency and material losses at the harmonic frequencies induce unusual intensity-dependent phenomena. We predict that the second-order nonlinearity of a low-damping, epsilon-near-zero slab produces an optical limiting effect that mimics a two-photon absorption process. Anomalous absorption profiles that depend on low permittivity values at the pump frequency are also predicted for third-order nonlinearities. These findings suggest new opportunities for all-optical light control and novel ways to design reconfigurable and tunable nonlinear devices.

Binary-Signal Recovery

NASA Technical Reports Server (NTRS)

Griebeler, Elmer L.

2011-01-01

Binary communication through long cables, opto-isolators, isolating transformers, or repeaters can become distorted in characteristic ways. The usual solution is to slow the communication rate, change to a different method, or improve the communication media. It would help if the characteristic distortions could be accommodated at the receiving end to ease the communication problem. The distortions come from loss of the high-frequency content, which adds slopes to the transitions from ones to zeroes and zeroes to ones. This weakens the definition of the ones and zeroes in the time domain. The other major distortion is the reduction of low frequency, which causes the voltage that defines the ones or zeroes to drift out of recognizable range. This development describes a method for recovering a binary data stream from a signal that has been subjected to a loss of both higher-frequency content and low-frequency content that is essential to define the difference between ones and zeroes. The method makes use of the frequency structure of the waveform created by the data stream, and then enhances the characteristics related to the data to reconstruct the binary switching pattern. A major issue is simplicity. The approach taken here is to take the first derivative of the signal and then feed it to a hysteresis switch. This is equivalent in practice to using a non-resonant band pass filter feeding a Schmitt trigger. Obviously, the derivative signal needs to be offset to halfway between the thresholds of the hysteresis switch, and amplified so that the derivatives reliably exceed the thresholds. A transition from a zero to a one is the most substantial, fastest plus movement of voltage, and therefore will create the largest plus first derivative pulse. Since the quiet state of the derivative is sitting between the hysteresis thresholds, the plus pulse exceeds the plus threshold, switching the hysteresis switch plus, which re-establishes the data zero to one transition, except now at the logic levels of the receiving circuit. Similarly, a transition from a one to a zero will be the most substantial and fastest minus movement of voltage and therefore will create the largest minus first derivative pulse. The minus pulse exceeds the minus threshold, switching the hysteresis switch minus, which re-establishes the data one to zero transition. This innovation has a large increase in tolerance for the degradation of the binary pattern of ones and zeroes, and can reject the introduction of noise in the form of low frequencies that can cause the voltage pattern to drift up or down, and also higher frequencies that are beyond the recognizable content in the binary transitions.

Roll-to-roll nanopatterning using jet and flash imprint lithography

NASA Astrophysics Data System (ADS)

Ahn, Sean; Ganapathisubramanian, Maha; Miller, Mike; Yang, Jack; Choi, Jin; Xu, Frank; Resnick, Douglas J.; Sreenivasan, S. V.

2012-03-01

The ability to pattern materials at the nanoscale can enable a variety of applications ranging from high density data storage, displays, photonic devices and CMOS integrated circuits to emerging applications in the biomedical and energy sectors. These applications require varying levels of pattern control, short and long range order, and have varying cost tolerances. Extremely large area R2R manufacturing on flexible substrates is ubiquitous for applications such as paper and plastic processing. It combines the benefits of high speed and inexpensive substrates to deliver a commodity product at low cost. The challenge is to extend this approach to the realm of nanopatterning and realize similar benefits. The cost of manufacturing is typically driven by speed (or throughput), tool complexity, cost of consumables (materials used, mold or master cost, etc.), substrate cost, and the downstream processing required (annealing, deposition, etching, etc.). In order to achieve low cost nanopatterning, it is imperative to move towards high speed imprinting, less complex tools, near zero waste of consumables and low cost substrates. The Jet and Flash Imprint Lithography (J-FILTM) process uses drop dispensing of UV curable resists to assist high resolution patterning for subsequent dry etch pattern transfer. The technology is actively being used to develop solutions for memory markets including Flash memory and patterned media for hard disk drives. In this paper we address the key challenges for roll based nanopatterning by introducing a novel concept: Ink Jet based Roll-to-Roll Nanopatterning. To address this challenge, we have introduced a J-FIL based demonstrator product, the LithoFlex 100. Topics that are discussed in the paper include tool design and process performance. In addition, we have used the LithoFlex 100 to fabricate high performance wire grid polarizers on flexible polycarbonate (PC) films. Transmission of better than 80% and extinction ratios on the order of 4500 have been achieved.

A pseudo-equilibrium thermodynamic model of information processing in nonlinear brain dynamics.

PubMed

Freeman, Walter J

2008-01-01

Computational models of brain dynamics fall short of performance in speed and robustness of pattern recognition in detecting minute but highly significant pattern fragments. A novel model employs the properties of thermodynamic systems operating far from equilibrium, which is analyzed by linearization near adaptive operating points using root locus techniques. Such systems construct order by dissipating energy. Reinforcement learning of conditioned stimuli creates a landscape of attractors and their basins in each sensory cortex by forming nerve cell assemblies in cortical connectivity. Retrieval of a selected category of stored knowledge is by a phase transition that is induced by a conditioned stimulus, and that leads to pattern self-organization. Near self-regulated criticality the cortical background activity displays aperiodic null spikes at which analytic amplitude nears zero, and which constitute a form of Rayleigh noise. Phase transitions in recognition and recall are initiated at null spikes in the presence of an input signal, owing to the high signal-to-noise ratio that facilitates capture of cortex by an attractor, even by very weak activity that is typically evoked by a conditioned stimulus.

Shuttle - Crew Candidates

NASA Image and Video Library

1979-03-01

Astronaut -Candidate (ASCAN) Guion S. Bluford and Aviation Safety Officer Charles F. Hayes got a unique perspective of their environment during a zero- gravity flight. They are aboard a KC-135 Aircraft, which flies a special pattern repeatedly to afford a series of 30-seconds-of-weightlessness sessions. Astronauts Bluford and Hayes are being assisted by C. P. Stanley of the Photography Branch of the Photographic Technology Division (PTD) at Johnson Space Center (JSC). Some medical studies and a Motion Sickness Experiment were conducted on this particular flight. Astronaut Bluford is one of 20 Scientist/ASCAN's who began training at JSC, 07/1978. 1. Dr. Jeffrey A. Hoffman - Zero-G 2. ASCAN Shannon Lucid - Zero-G 3. ASCAN Guion Bluford - Zero-G

Environmental Influences on Kelp Performance across the Reproductive Period: An Ecological Trade-Off between Gametophyte Survival and Growth?

PubMed Central

Mohring, Margaret B.; Kendrick, Gary A.; Wernberg, Thomas; Rule, Michael J.; Vanderklift, Mathew A.

2013-01-01

Most kelps (order Laminariales) exhibit distinct temporal patterns in zoospore production, gametogenesis and gametophyte reproduction. Natural fluctuations in ambient environmental conditions influence the intrinsic characteristics of gametes, which define their ability to tolerate varied conditions. The aim of this work was to document seasonal patterns in reproduction and gametophyte growth and survival of Ecklonia radiata (C. Agardh) J. Agardh in south-western Australia. These results were related to patterns in local environmental conditions in an attempt to ascertain which factors explain variation throughout the season. E. radiata was fertile (produced zoospores) for three and a half months over summer and autumn. Every two weeks during this time, gametophytes were grown in a range of temperatures (16–22°C) in the laboratory. Zoospore densities were highly variable among sample periods; however, zoospores released early in the season produced gametophytes which had greater rates of growth and survival, and these rates declined towards the end of the reproductive season. Growth rates of gametophytes were positively related to day length, with the fastest growing recruits released when the days were longest. Gametophytes consistently survived best in the lowest temperature (16°C), yet exhibited optimum growth in higher culture temperatures (20–22°C). These results suggest that E. radiata releases gametes when conditions are favourable for growth, and E. radiata gametophytes are tolerant of the range of temperatures observed at this location. E. radiata releases the healthiest gametophytes when day length and temperature conditions are optimal for better germination, growth, and sporophyte production, perhaps as a mechanism to help compete against other species for space and other resources. PMID:23755217

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride.

PubMed

Verma, Anurag; Bansal, Ashok K; Ghosh, Amitava; Pandit, Jayanta K

2012-06-01

Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L⁻¹ HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules.

EFFECT OF HYDROPHILIC AND HYDROPHOBIC POLYMER ON IN VITRO DISSOLUTION AND PERMEATION OF BISOPROLOL FUMARATE THROUGH TRANSDERMAL PATCH.

PubMed

Shabbir, Maryam; Ali, Sajid; Raza, Moosa; Sharif, Ali; Akhtar, Furoan Muhammad; Manan, Abdul; Fazli, Ali Raza; Younas, Neelofar; Manzoor, Iqra

2017-01-01

A matrix transdermal patch of bisoprolol fumarate was formulated with different concentrations of Eudragit RS 100 and Methocel E5 with PEG 400 as plasticizer by solvent evaporation technique. Tween 80 was added to the optimized patch to evaluate the effect of permeation enhancer at different concentration through the excised rabbit's skin. The patches were analyzed for weight variation, drug content, swelling index, erosion studies, moisture content, moisture uptake, water vapor transmission rate (WVTR) and water vapor permeability (WVP). In vitro dissolution test was carried out in USP dissolution apparatus V to select the optimized formulation. In vitr skin permeation studies were done in Franz diffusion cell using rabbit skin as a model membrane. The cumulative drug release and flux were determined to compare the result of test patches with a control patch. The greatest enhancement ratio (ER) was obtained in F03-PE with 30% Tween 80. F03-PE seemed to follow zero order kinetics with super case II mechanism of drug release. Statistical ANOVA suggested that there was a significant difference in formulations, steady flux and cumulative permeation rate at different Tween 80 concentrations.

Like-charged protein-polyelectrolyte complexation driven by charge patches

NASA Astrophysics Data System (ADS)

Yigit, Cemil; Heyda, Jan; Ballauff, Matthias; Dzubiella, Joachim

2015-08-01

We study the pair complexation of a single, highly charged polyelectrolyte (PE) chain (of 25 or 50 monomers) with like-charged patchy protein models (CPPMs) by means of implicit-solvent, explicit-salt Langevin dynamics computer simulations. Our previously introduced set of CPPMs embraces well-defined zero-, one-, and two-patched spherical globules each of the same net charge and (nanometer) size with mono- and multipole moments comparable to those of globular proteins with similar size. We observe large binding affinities between the CPPM and the like-charged PE in the tens of the thermal energy, kBT, that are favored by decreasing salt concentration and increasing charge of the patch(es). Our systematic analysis shows a clear correlation between the distance-resolved potentials of mean force, the number of ions released from the PE, and CPPM orientation effects. In particular, we find a novel two-site binding behavior for PEs in the case of two-patched CPPMs, where intermediate metastable complex structures are formed. In order to describe the salt-dependence of the binding affinity for mainly dipolar (one-patched) CPPMs, we introduce a combined counterion-release/Debye-Hückel model that quantitatively captures the essential physics of electrostatic complexation in our systems.

Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its hygroscopic character improvement and investigation of in vitro/in vivo dissolution properties.

PubMed

Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

2007-04-01

Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 2(3) full factorial design. In vitro studies, the 2(3) full factorial design was utilized to search for the optimal SR pellets with specific release rate at different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24, 33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism (n=0.93). The results of moisture absorption by Karl Fischer has shown the optimum SR pellets at 25 degrees C/60% RH, 30 degrees C/65% RH, and 40 degrees C/75% RH chambers from 1 hr-4 weeks, attributing that the moisture absorption was not significantly increased. In the in vivo study, the results of the bioavailability data showed the Tmax (from 0.65+/-0.082 hr-4.82+/-2.12 hr) and AUC0-30 hr (from 734.88+/-230.68 ng/mL.hr-1454.86+/-319.28 ng/mL.hr) were prolonged and increased, as well as Cmax (from 251.87+/-27.51 ng/mL-115.08+/-14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with commercial immediate-release (IR) tablets. Furthermore, a good linear regression relationship (r=0.9943) was observed between the fraction dissolution and fraction absorption for the optimum SR pellets. In this study, the formulation design not only improved the hygroscopic character of PB but also achieved the SR effect.

"Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

PubMed

Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

2011-01-01

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

PubMed

Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

2014-07-01

The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies.

PubMed

Trapani, Adriana; Laquintana, Valentino; Denora, Nunzio; Lopedota, Angela; Cutrignelli, Annalisa; Franco, Massimo; Trapani, Giuseppe; Liso, Gaetano

2007-01-01

The aim of this study was to encapsulate glutathione (GSH) alone or in combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in Eudragit RS 100 microparticles (MPs), and to evaluate these novel delivery systems for oral administration of the considered tripeptide. The MPs were prepared by an O/O emulsion-solvent evaporation method according to a multilevel experimental design involving the volume of liquid paraffin, the HP-beta-CD amount, and the drug/polymer ratio as independent variables. The effects of these parameters on particle size, entrapment efficiency, and drug release were investigated. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GSH and Eudragit RS 100 polymer and to characterize the physical state of drug within the MPs. The release profiles of GSH from MPs were examined in vitro at pH 1.2, 6.8. and 7.4 using the USP III (BioDis) dissolution apparatus. In general, a slow and zero-order release of GSH from MPs at pH 1.2 occurred, while at higher pH values considerable amounts of glutathione disulfide (i.e., GSSG) were observed. The enzymatic stability and the intestinal permeability of some GSH-containing MPs were assessed by using pepsin, alpha-chymotrypsin, gamma-glutamyl-transpeptidase and everted frog intestinal sac methodology, respectively. The results suggest that GSH-loaded Eudragit RS 100 MPs containing HP-beta-CD represent a new sustained GSH delivery system useful for the oral administration of the examined tripeptide.

Design of Block Copolymer Costabilized Nonionic Microemulsions and Their In Vitro and In Vivo Assessment as Carriers for Sustained Regional Delivery of Ibuprofen via Topical Administration.

PubMed

Djekic, Ljiljana; Martinovic, Martina; Stepanović-Petrović, Radica; Tomić, Maja; Micov, Ana; Primorac, Marija

2015-08-01

Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-in-water microemulsions with Newtonian flow behavior, low viscosity (from 368 ± 38 to 916 ± 46 mPa s), and average droplet size from 14.79 ± 0.31 to 16.54 ± 0.75 nm. Ibuprofen in vitro release from the microemulsions was in accordance with zero-order kinetics (R0(2) > 0.99) for at least 12 h. The maximum drug release rate (3.55%h(-1) ) was from the microemulsion M3 comprising 16%, w/w of poloxamer 407. The release rate of ibuprofen from the reference hydrogel followed Higuchi kinetics (RH(2) > 0.99), and drug amount released after the 6th hour was negligible. In a rat model of inflammation, the microemulsion M3 was significantly more efficacious than the reference hydrogel in exerting antihyperalgesic effects in prophylactic topical treatment, whereas they were comparable in therapeutic treatment as well as in producing antiedematous effect in both protocols. No obvious skin irritation was observed in in vivo studies. The developed nonionic surfactants-based microemulsions containing the optimal concentration of poloxamer 407 could be promising carriers for sustained regional delivery of ibuprofen via topical administration. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Unraveling the physics of vertical organic field effect transistors through nanoscale engineering of a self-assembled transparent electrode.

PubMed

Ben-Sasson, Ariel J; Tessler, Nir

2012-09-12

While organic transistors' performances are continually pushed to achieve lower power consumption, higher working frequencies, and higher current densities, a new type of organic transistors characterized by a vertical architecture offers a radically different design approach to outperform its traditional counterparts. Naturally, the distinct vertical architecture gives way to different governing physical ground rules and structural key features such as the need for an embedded transparent electrode. In this paper, we make use of a zero-frequency electric field-transparent patterned electrode produced through block-copolymer self-assembly based lithography to control the performances of the vertical organic field effect transistor (VOFET) and to study its governing physical mechanisms. Unlike other VOFET structures, this design, involving well-defined electrode architecture, is fully tractable, allowing for detailed modeling, analysis, and optimization. We provide for the first time a complete account of the physics underpinning the VOFET operation, considering two complementary mechanisms: the virtual contact formation (Schottky barrier lowering) and the induced potential barrier (solid-state triode-like shielding). We demonstrate how each mechanism, separately, accounts for the link between controllable nanoscale structural modifications in the patterned electrode and the VOFET performances. For example, the ON/OFF current ratio increases by up to 2 orders of magnitude when the perforations aspect ratio (height/width) decreases from ∼0.2 to ∼0.1. The patterned electrode is demonstrated to be not only penetrable to zero-frequency electric fields but also transparent in the visible spectrum, featuring uniformity, spike-free structure, material diversity, amenability with flexible surfaces, low sheet resistance (20-2000 Ω sq(-1)) and high transparency (60-90%). The excellent layer transparency of the patterned electrode and the VOFET's exceptional electrical performances make them both promising elements for future transparent and/or efficient organic electronics.

Probabilistic model of nonlinear penalties due to collision-induced timing jitter for calculation of the bit error ratio in wavelength-division-multiplexed return-to-zero systems

NASA Astrophysics Data System (ADS)

Sinkin, Oleg V.; Grigoryan, Vladimir S.; Menyuk, Curtis R.

2006-12-01

We introduce a fully deterministic, computationally efficient method for characterizing the effect of nonlinearity in optical fiber transmission systems that utilize wavelength-division multiplexing and return-to-zero modulation. The method accurately accounts for bit-pattern-dependent nonlinear distortion due to collision-induced timing jitter and for amplifier noise. We apply this method to calculate the error probability as a function of channel spacing in a prototypical multichannel return-to-zero undersea system.

The Extended Pulsar Magnetosphere

NASA Technical Reports Server (NTRS)

Constantinos, Kalapotharakos; Demosthenes, Kazanas; Ioannis, Contopoulos

2012-01-01

We present the structure of the 3D ideal MHD pulsar magnetosphere to a radius ten times that of the light cylinder, a distance about an order of magnitude larger than any previous such numerical treatment. Its overall structure exhibits a stable, smooth, well-defined undulating current sheet which approaches the kinematic split monopole solution of Bogovalov 1999 only after a careful introduction of diffusivity even in the highest resolution simulations. It also exhibits an intriguing spiral region at the crossing of two zero charge surfaces on the current sheet, which shows a destabilizing behavior more prominent in higher resolution simulations. We discuss the possibility that this region is physically (and not numerically) unstable. Finally, we present the spiral pulsar antenna radiation pattern.

Endangered Right Whales Enhance Primary Productivity in the Bay of Fundy

PubMed Central

Roman, Joe; Nevins, John; Altabet, Mark; Koopman, Heather; McCarthy, James

2016-01-01

Marine mammals have recently been documented as important facilitators of rapid and efficient nutrient recycling in coastal and offshore waters. Whales enhance phytoplankton nutrition by releasing fecal plumes near the surface after feeding and by migrating from highly productive, high-latitude feeding areas to low-latitude nutrient-poor calving areas. In this study, we measured NH4+ and PO43- release rates from the feces of North Atlantic right whales (Eubalaena glacialis), a highly endangered baleen whale. Samples for this species were primarily collected by locating aggregations of whales in surface-active groups (SAGs), which typically consist of a central female surrounded by males competing for sexual activity. When freshly collected feces were incubated in seawater, high initial rates of N release were generally observed, which decreased to near zero within 24 hours of sampling, a pattern that is consistent with the active role of gut microflora on fecal particles. We estimate that at least 10% of particulate N in whale feces becomes available as NH4+ within 24 hours of defecation. Phosphorous was also abundant in fecal samples: initial release rates of PO43- were higher than for NH4+, yielding low N/P nutrient ratios over the course of our experiments. The rate of PO43- release was thus more than sufficient to preclude the possibility that nitrogenous nutrients supplied by whales would lead to phytoplankton production limited by P availability. Phytoplankton growth experiments indicated that NH4+ released from whale feces enhance productivity, as would be expected, with no evidence that fecal metabolites suppress growth. Although North Atlantic right whales are currently rare (approximately 450 individuals), they once numbered about 14,000 and likely played a substantial role in recycling nutrients in areas where they gathered to feed and mate. Even though the NH4+ released from fresh whale fecal material is a small fraction of total whale fecal nitrogen, and recognizing the fact that the additional nitrogen released in whale urine would be difficult to measure in a field study, the results of this study support the idea that the distinctive isotopic signature of the released NH4+ could be used to provide a conservative estimate of the contribution of the whale pump to primary productivity in coastal regions where whales congregate. PMID:27331902

Endangered Right Whales Enhance Primary Productivity in the Bay of Fundy.

PubMed

Roman, Joe; Nevins, John; Altabet, Mark; Koopman, Heather; McCarthy, James

2016-01-01

Marine mammals have recently been documented as important facilitators of rapid and efficient nutrient recycling in coastal and offshore waters. Whales enhance phytoplankton nutrition by releasing fecal plumes near the surface after feeding and by migrating from highly productive, high-latitude feeding areas to low-latitude nutrient-poor calving areas. In this study, we measured NH4+ and PO43- release rates from the feces of North Atlantic right whales (Eubalaena glacialis), a highly endangered baleen whale. Samples for this species were primarily collected by locating aggregations of whales in surface-active groups (SAGs), which typically consist of a central female surrounded by males competing for sexual activity. When freshly collected feces were incubated in seawater, high initial rates of N release were generally observed, which decreased to near zero within 24 hours of sampling, a pattern that is consistent with the active role of gut microflora on fecal particles. We estimate that at least 10% of particulate N in whale feces becomes available as NH4+ within 24 hours of defecation. Phosphorous was also abundant in fecal samples: initial release rates of PO43- were higher than for NH4+, yielding low N/P nutrient ratios over the course of our experiments. The rate of PO43- release was thus more than sufficient to preclude the possibility that nitrogenous nutrients supplied by whales would lead to phytoplankton production limited by P availability. Phytoplankton growth experiments indicated that NH4+ released from whale feces enhance productivity, as would be expected, with no evidence that fecal metabolites suppress growth. Although North Atlantic right whales are currently rare (approximately 450 individuals), they once numbered about 14,000 and likely played a substantial role in recycling nutrients in areas where they gathered to feed and mate. Even though the NH4+ released from fresh whale fecal material is a small fraction of total whale fecal nitrogen, and recognizing the fact that the additional nitrogen released in whale urine would be difficult to measure in a field study, the results of this study support the idea that the distinctive isotopic signature of the released NH4+ could be used to provide a conservative estimate of the contribution of the whale pump to primary productivity in coastal regions where whales congregate.

78 FR 14867 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... how the NSX System may execute certain types of Zero Display Reserve Orders \\4\\ that are pegged to the midpoint between the Protected BBO in subpennies. NSX Rule 11.3(c) provides that a Zero Display Reserve... the System rounds executions in securities priced less than $1.00 per share resulting from a Zero...

Designing and Constructing an Exemplar Zero Carbon Primary School in the City of Exeter, United Kingdom

ERIC Educational Resources Information Center

Tatchell, Arthur

2012-01-01

The United Kingdom's (UK) 2008 Budget announced the government's ambition that all new non-domestic buildings should be zero carbon from 2016. In order to take this goal forward, the Department for Children, Schools and Families (DCSF) established the Zero Carbon Task Force (ZCTF); its objective was to advise on how England can achieve this…

Host cell recruitment patterns by bone morphogenetic protein-2 releasing hyaluronic acid hydrogels in a mouse subcutaneous environment.

PubMed

Todeschi, Maria R; El Backly, Rania M; Varghese, Oommen P; Hilborn, Jöns; Cancedda, Ranieri; Mastrogiacomo, Maddalena

2017-07-01

This study aimed to identify host cell recruitment patterns in a mouse model in response to rhBMP-2 releasing hyaluronic acid hydrogels and influence of added nano-hydroxyapatite particles on rhBMP-2 release and pattern of bone formation. Implanted gels were retrieved after implantation and cells were enzymatically dissociated for flow cytometric analysis. Percentages of macrophages, progenitor endothelial cells and putative mesenchymal stem cells were measured. Implants were evaluated for BMP-2 release by ELISA and by histology to monitor tissue formation. Hyaluronic acid+BMP-2 gels influenced the inflammatory response in the bone healing microenvironment. Host-derived putative mesenchymal stem cells were major contributors. Addition of hydroxyapatite nanoparticles modified the release pattern of rhBMP-2, resulting in enhanced bone formation.

Skill Analysis of the Wrist Release in the Golf Swings Utilizing Shaft Elasticity

NASA Astrophysics Data System (ADS)

Suzuki, Soichiro; Hoshino, Yohei; Kobayashi, Yukinori

This study analyzes the skill component of the wrist release in the golf swing by employing a three-dimensional dynamic model considering vibration of the club shaft. It is observed that professional and expert golfers relax their wrists in the swing motion as a "natural" or "late" release. Thus, the relationship between the timing of the wrist release and the shaft vibration is examined in this study. First, it is demonstrated that "natural release" at the zero-crossing point of the bending vibration of the shaft efficiently increases the head speed at impact. In the next step, the "late hitting" condition is imposed upon the model. It is demonstrated that "late hitting" could further improve the efficiency of the swing motion. Finally, the skill component in the wrist release for the long drive is experimentally verified by measuring the movement of the wrist and the dynamic deformation of the shaft during the downswing.

Modeling drug release from PVAc/PVP matrix tablets.

PubMed

Siepmann, F; Eckart, K; Maschke, A; Kolter, K; Siepmann, J

2010-01-25

Kollidon SR-based matrix tablets containing various amounts of diprophylline were prepared and thoroughly characterized in vitro. This includes drug release measurements in 0.1M HCl and phosphate buffer pH 7.4, monitoring of changes in the tablet's height and diameter, morphology as well as dry mass upon exposure to the release media. Based on these experimental results, a mechanistic realistic mathematical theory is proposed, taking into account the given initial and boundary conditions as well as radial and axial mass transport in cylinders. Importantly, good agreement between theory and experiment was obtained in all cases, indicating that drug diffusion with constant diffusivity is the dominant mass transport mechanism in these systems. Furthermore, the proposed theory was used to quantitatively predict the effects of the initial tablet height and diameter on the resulting drug release patterns. These theoretical predictions were compared with independently measured drug release kinetics. Good agreement was observed in all cases, proving the validity of the mathematical theory and illustrating the latter's practical benefit: The model can help to significantly facilitate the recipe optimization of this type of advanced drug delivery systems in order to achieve a desired release profile. Copyright 2009 Elsevier B.V. All rights reserved.

Two-nucleon S10 amplitude zero in chiral effective field theory

NASA Astrophysics Data System (ADS)

Sánchez, M. Sánchez; Yang, C.-J.; Long, Bingwei; van Kolck, U.

2018-02-01

We present a new rearrangement of short-range interactions in the S10 nucleon-nucleon channel within chiral effective field theory. This is intended to address the slow convergence of Weinberg's scheme, which we attribute to its failure to reproduce the amplitude zero (scattering momentum ≃340 MeV) at leading order. After the power counting scheme is modified to accommodate the zero at leading order, it includes subleading corrections perturbatively in a way that is consistent with renormalization-group invariance. Systematic improvement is shown at next-to-leading order, and we obtain results that fit empirical phase shifts remarkably well all the way up to the pion-production threshold. An approach in which pions have been integrated out is included, which allows us to derive analytic results that also fit phenomenology surprisingly well.

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

Gerber, S.; Jang, H.; Nojiri, H.

In this study, charge density wave (CDW) correlations have recently been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from that measured by x-ray scattering at zero and low fields. Here we combine a pulsed magnet with an x-ray free electron laser to characterize the CDW in YBa 2Cu 3O 6.67 via x-ray scattering in fields up to 28 Tesla. While the zero-field CDW order, which develops below T ~ 150 K, is essentially two-dimensional, at lower temperature and beyond 15 Tesla, another three-dimensionally ordered CDW emerges. Themore » field-induced CDW onsets around the zero-field superconducting transition temperature, yet the incommensurate in-plane ordering vector is field-independent. This implies that the two forms of CDW and high-temperature superconductivity are intimately linked.« less

Observations and theory of the AMPTE magnetotail barium releases

NASA Technical Reports Server (NTRS)

Bernhardt, P. A.; Roussel-Dupre, R. A.; Pongratz, M. B.; Haerendel, G.; Valenzuela, A.

1987-01-01

The barium releases in the magnetotail during the Active Magnetospheric Particle Tracer Explorers (AMPTE) operation were monitored by ground-based imagers and by instruments on the Ion Release Module. After each release, the data show the formation of a structured diamagnetic cavity. The cavity grows until the dynamic pressure of the expanding ions balances the magnetic pressure on its surface. The magnetic field inside the cavity is zero. The barium ions collect on the surface of the cavity, producing a shell. Plasma irregularities form along magnetic field lines draped over the surface of the cavity. The scale size of the irregularities is nearly equal to the thickness of the shell. The evolution and structuring of the diamagnetic cavity are modeled using magnetohydrodynamics theory.

Pharmaceutical Evaluation of Cefuroxime Axetil Tablets Available in Drug Market of Pakistan

PubMed Central

Israr, F.; Mahmood, Z. A.; Hassan, F.; Hasan, S. M. F.

2016-01-01

Cefuroxime is a second generation cephalosporin antibiotic with a broad spectrum activity against Gram positive and Gram negative bacteria. The purpose of this research work was to evaluate the pharmaceutical quality standards of four different brands of cefuroxime axetil 125 mg tablets with different price ranges purchased from retail pharmacies of Pakistan. The brands were tested for physicochemical evaluation and in vitro dissolution studies in different medium like 0.07N HCl, distilled water, 0.1N HCl of pH 1.2 and phosphate buffers of pH 4.5 and pH 6.8. Statistical analysis, model dependent (zero order, first order, Korsmeyer-Peppas, Hixson-Crowell, Weibull) and model independent (Difference f1, similarity f2) approaches were applied to multiple dissolution profile of all brands. All brands were found to be similar with reference and meeting the compendial quality standard. Inter brand variation was observed in disintegration time and assay which was resulted in significant differences (P<0.05) in drug release data and Weibull was observed as best fill model. PMID:27168677

Rifaximin Stability: A Look at UV, IR, HPLC, and Turbidimetry Methods.

PubMed

Kogawa, Ana Carolina; Salgado, Hérida Regina Nunes

2018-03-01

The study of the stability of medicines is mandated by the International Conference on Harmonization and the World Health Organization. Rifaximin, an antimicrobial marketed in the form of tablets, has no record of stability studies. Thus, the objective of the present work was to investigate the behavior and stability of rifaximin tablets for 6 months under simultaneous conditions of temperature and humidity by UV, IR, HPLC, and turbidimetry techniques. After 6 months of stability study, rifaximin tablets were shown to obey zero-order kinetics when analyzed by physicochemical methods and second-order kinetics when analyzed by a microbiological method. However, the UV method was not suitable for the evaluation of rifaximin. IR, HPLC, and turbidimetry methods can already be used to evaluate the stability of rifaximin tablets. It is important to analyze products with more than one type of method before releasing results mainly in the case of antimicrobial products in which the association of physicochemical and microbiological techniques must be a rule. Rifaximin tablets can be considered stable after 6 months under conditions of 40 ± 2°C and 75 ± 5% relative humidity.

Renormalization of the weak hadronic current in the nuclear medium

NASA Astrophysics Data System (ADS)

Siiskonen, T.; Hjorth-Jensen, M.; Suhonen, J.

2001-05-01

The renormalization of the weak charge-changing hadronic current as a function of the reaction energy release is studied at the nucleonic level. We have calculated the average quenching factors for each type of current (vector, axial vector, and induced pseudoscalar). The obtained quenching in the axial vector part is, at zero momentum transfer, 19% for the 1s0d shell and 23% in the 1p0f shell. We have extended the calculations also to heavier systems such as 56Ni and 100Sn, where we obtain stronger quenchings, 44% and 59%, respectively. Gamow-Teller-type transitions are discussed, along with the higher-order matrix elements. The quenching factors are constant up to roughly 60 MeV momentum transfer. Therefore the use of energy-independent quenching factors in beta decay is justified. We also found that going beyond the zeroth and first order operators (in inverse nucleon mass) does not give any substantial contribution. The extracted renormalization to the ratio CP/CA at q=100 MeV is -3.5%, -7.1%, -28.6%, and +8.7% for mass 16, 40, 56, and 100, respectively.

Cometary nucleus release experiments and ice physics

NASA Technical Reports Server (NTRS)

Huebner, W. F.

1976-01-01

Some physical and chemical processes involved in the evaporation and sublimation of mixtures of frozen gases are discussed. Effects of zero gravity, vacuum, and solar radiation are emphasized. Relevant experiments that can be carried out with the aid of the space shuttle are proposed.

Simulation of Cell Patterning Triggered by Cell Death and Differential Adhesion in Drosophila Wing.

PubMed

Nagai, Tatsuzo; Honda, Hisao; Takemura, Masahiko

2018-02-27

The Drosophila wing exhibits a well-ordered cell pattern, especially along the posterior margin, where hair cells are arranged in a zigzag pattern in the lateral view. Based on an experimental result observed during metamorphosis of Drosophila, we considered that a pattern of initial cells autonomously develops to the zigzag pattern through cell differentiation, intercellular communication, and cell death (apoptosis) and performed computer simulations of a cell-based model of vertex dynamics for tissues. The model describes the epithelial tissue as a monolayer cell sheet of polyhedral cells. Their vertices move according to equations of motion, minimizing the sum total of the interfacial and elastic energies of cells. The interfacial energy densities between cells are introduced consistently with an ideal zigzag cell pattern, extracted from the experimental result. The apoptosis of cells is modeled by gradually reducing their equilibrium volume to zero and by assuming that the hair cells prohibit neighboring cells from undergoing apoptosis. Based on experimental observations, we also assumed wing elongation along the proximal-distal axis. Starting with an initial cell pattern similar to the micrograph experimentally obtained just before apoptosis, we carried out the simulations according to the model mentioned above and successfully reproduced the ideal zigzag cell pattern. This elucidates a physical mechanism of patterning triggered by cell apoptosis theoretically and exemplifies, to our knowledge, a new framework to study apoptosis-induced patterning. We conclude that the zigzag cell pattern is formed by an autonomous communicative process among the participant cells. Copyright © 2018 Biophysical Society. All rights reserved.

Molecular and Metabolic Adaptations of Lactococcus lactis at Near-Zero Growth Rates

PubMed Central

Ercan, Onur; Wels, Michiel; Smid, Eddy J.

2014-01-01

This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state by using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid fermentations during retentostat cultivation, which appeared to be controlled at the level of transcription of the corresponding pyruvate dissipation-encoding genes. During retentostat cultivation, cells continued to consume several amino acids but also produced specific amino acids, which may derive from the conversion of glycolytic intermediates. We identify a novel motif containing CTGTCAG in the upstream regions of several genes related to amino acid conversion, which we propose to be the target site for CodY in L. lactis KF147. Finally, under extremely low carbon availability, carbon catabolite repression was progressively relieved and alternative catabolic functions were found to be highly expressed, which was confirmed by enhanced initial acidification rates on various sugars in cells obtained from near-zero-growth cultures. The present integrated transcriptome and metabolite (amino acids and previously reported fermentation end products) study provides molecular understanding of the adaptation of L. lactis to conditions supporting low growth rates and expands our earlier analysis of the quantitative physiology of this bacterium at near-zero growth rates toward gene regulation patterns involved in zero-growth adaptation. PMID:25344239

Canopy and leaf composition drive patterns of nutrient release from pruning residues in a coffee agroforest.

PubMed

Tully, Katherine L; Lawrence, Deborah

2012-06-01

In a coffee agroforest, the crop is cultivated under the shade of fruit-bearing and nitrogen (N)-fixing trees. These trees are periodically pruned to promote flowering and fruiting as well as to make nutrients stored in tree biomass available to plants. We investigated the effect of canopy composition and substrate quality on decomposition rates and patterns of nutrient release from pruning residues in a coffee agroforest located in Costa Rica's Central Valley. Initial phosphorus (P) release was enhanced under a canopy composed solely of N-fixing, Erythrina poeppigiana compared to a mixed canopy of Erythrina and Musa acuminata (banana). Both initial and final N release were similar under the two canopy types. However, after five months of decomposition, a higher proportion of initial N had been released under the single canopy. Although patterns of decomposition and nutrient release were not predicted by initial substrate quality, mass loss in leaf mixtures rates were well predicted by mean mass loss of their component species. This study identifies specific pruning regimes that may regulate N and P release during crucial growth periods, and it suggests that strategic pruning can enhance nutrient availability. For example, during the onset of rapid fruit growth, a two-species mixture may release more P than a three-species mixture. However, by the time of the harvest, the two- and three-species mixtures have released roughly the same amount of N and P. These nutrients do not always follow the same pattern, as N release can be maximized in single-species substrates, while P release is often facilitated in species mixtures. Our study indicates the importance of management practices in mediating patterns of nutrient release. Future research should investigate how canopy composition and farm management can also mediate on-farm nutrient losses.

Generation of a non-zero discord bipartite state with classical second-order interference.

PubMed

Choi, Yujun; Hong, Kang-Hee; Lim, Hyang-Tag; Yune, Jiwon; Kwon, Osung; Han, Sang-Wook; Oh, Kyunghwan; Kim, Yoon-Ho; Kim, Yong-Su; Moon, Sung

2017-02-06

We report an investigation on quantum discord in classical second-order interference. In particular, we theoretically show that a bipartite state with D = 0.311 of discord can be generated via classical second-order interference. We also experimentally verify the theory by obtaining D = 0.197 ± 0.060 of non-zero discord state. Together with the fact that the nonclassicalities originated from physical constraints and information theoretic perspectives are not equivalent, this result provides an insight to understand the nature of quantum discord.

Water Sustainability Assessments for Four Net Zero Water Installations

DTIC Science & Technology

2013-12-01

es ea rc h La bo ra to ry Elisabeth M. Jenicek, Laura Curvey, Yuki Cruz, and Rachel Phillips December 2013 Approved for public release...for the Army, the Department of Defense, civilian agencies, and our nation’s public good. Find out more at www.erdc.usace.army.mil. To search for... public release; distribution is unlimited. Prepared for DASA(IEE) Arlington, VA 22202 Under Work Unit H83G56 ERDC/CERL TR-13-25 ii Abstract The

Near-zero thermal expansion in magnetically ordered state in dysprosium at high pressures and low temperatures

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

Hope, Kevin M.; Samudrala, Gopi K.; Vohra, Yogesh K.

The atomic volume of rare earth metal Dysprosium (Dy) has been measured up to high pressures of 35 GPa and low temperatures between 200 K and 7 K in a diamond anvil cell using angle dispersive x-ray diffraction at a synchrotron source. The hexagonal close-packed (hcp), alpha-Samarium (α-Sm), and double hexagonal close packed (dhcp) phases are observed to be stable in Dy under high-pressure and low-temperature conditions achieved in our experiments. Dy is known to undergo magnetic ordering below 176 K at ambient pressure with magnetic ordering Néel temperature (T N) that changes rapidly with increasing pressure. Our experimental measurementmore » shows that Dy has near-zero thermal expansion in the magnetically ordered state and normal thermal expansion in the paramagnetic state for all the three known high pressure phases (hcp, α-Sm, and dhcp) to 35 GPa. This near-zero thermal expansion behavior in Dy is observed below the magnetic ordering temperature T N at all pressures up to 35 GPa.« less

Near-zero thermal expansion in magnetically ordered state in dysprosium at high pressures and low temperatures

DOE PAGES

Hope, Kevin M.; Samudrala, Gopi K.; Vohra, Yogesh K.

2017-01-01

The atomic volume of rare earth metal Dysprosium (Dy) has been measured up to high pressures of 35 GPa and low temperatures between 200 K and 7 K in a diamond anvil cell using angle dispersive x-ray diffraction at a synchrotron source. The hexagonal close-packed (hcp), alpha-Samarium (α-Sm), and double hexagonal close packed (dhcp) phases are observed to be stable in Dy under high-pressure and low-temperature conditions achieved in our experiments. Dy is known to undergo magnetic ordering below 176 K at ambient pressure with magnetic ordering Néel temperature (T N) that changes rapidly with increasing pressure. Our experimental measurementmore » shows that Dy has near-zero thermal expansion in the magnetically ordered state and normal thermal expansion in the paramagnetic state for all the three known high pressure phases (hcp, α-Sm, and dhcp) to 35 GPa. This near-zero thermal expansion behavior in Dy is observed below the magnetic ordering temperature T N at all pressures up to 35 GPa.« less

Born’s rule as signature of a superclassical current algebra

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

Fussy, S.; Mesa Pascasio, J.; Institute for Atomic and Subatomic Physics, Vienna University of Technology, Operng. 9, 1040 Vienna

2014-04-15

We present a new tool for calculating the interference patterns and particle trajectories of a double-, three- and N-slit system on the basis of an emergent sub-quantum theory developed by our group throughout the last years. The quantum itself is considered as an emergent system representing an off-equilibrium steady state oscillation maintained by a constant throughput of energy provided by a classical zero-point energy field. We introduce the concept of a “relational causality” which allows for evaluating structural interdependences of different systems levels, i.e. in our case of the relations between partial and total probability density currents, respectively. Combined with themore » application of 21st century classical physics like, e.g., modern nonequilibrium thermodynamics, we thus arrive at a “superclassical” theory. Within this framework, the proposed current algebra directly leads to a new formulation of the guiding equation which is equivalent to the original one of the de Broglie–Bohm theory. By proving the absence of third order interferences in three-path systems it is shown that Born’s rule is a natural consequence of our theory. Considering the series of one-, double-, or, generally, of N-slit systems, with the first appearance of an interference term in the double slit case, we can explain the violation of Sorkin’s first order sum rule, just as the validity of all higher order sum rules. Moreover, the Talbot patterns and Talbot distance for an arbitrary N-slit device can be reproduced exactly by our model without any quantum physics tool. -- Highlights: •Calculating the interference patterns and particle trajectories of a double-, three- and N-slit system. •Deriving a new formulation of the guiding equation equivalent to the de Broglie–Bohm one. •Proving the absence of third order interferences and thus explaining Born’s rule. •Explaining the violation of Sorkin’s order sum rules. •Classical simulation of Talbot patterns and exact reproduction of Talbot distance for N slits.« less

Propagation in and scattering from a matched metamaterial having a zero index of refraction.

PubMed

Ziolkowski, Richard W

2004-10-01

Planar metamaterials that exhibit a zero index of refraction have been realized experimentally by several research groups. Their existence stimulated the present investigation, which details the properties of a passive, dispersive metamaterial that is matched to free space and has an index of refraction equal to zero. Thus, unlike previous zero-index investigations, both the permittivity and permeability are zero here at a specified frequency. One-, two-, and three-dimensional source problems are treated analytically. The one- and two-dimensional source problem results are confirmed numerically with finite difference time domain (FDTD) simulations. The FDTD simulator is also used to treat the corresponding one- and two-dimensional scattering problems. It is shown that in both the source and scattering configurations the electromagnetic fields in a matched zero-index medium take on a static character in space, yet remain dynamic in time, in such a manner that the underlying physics remains associated with propagating fields. Zero phase variation at various points in the zero-index medium is demonstrated once steady-state conditions are obtained. These behaviors are used to illustrate why a zero-index metamaterial, such as a zero-index electromagnetic band-gap structured medium, significantly narrows the far-field pattern associated with an antenna located within it. They are also used to show how a matched zero-index slab could be used to transform curved wave fronts into planar ones.

Effect of zero magnetic field on cardiovascular system and microcirculation

NASA Astrophysics Data System (ADS)

Gurfinkel, Yu. I.; At'kov, O. Yu.; Vasin, A. L.; Breus, T. K.; Sasonko, M. L.; Pishchalnikov, R. Yu.

2016-02-01

The effects of zero magnetic field conditions on cardiovascular system of healthy adults have been studied. In order to generate zero magnetic field, the facility for magnetic fields modeling ;ARFA; has been used. Parameters of the capillary blood flow, blood pressure, and the electrocardiogram (ECG) monitoring were measured during the study. All subjects were tested twice: in zero magnetic field and, for comparison, in sham condition. The obtained results during 60 minutes of zero magnetic field exposure demonstrate a clear effect on cardiovascular system and microcirculation. The results of our experiments can be used in studies of long-term stay in hypo-magnetic conditions during interplanetary missions.

Optical properties of iron oxides

NASA Astrophysics Data System (ADS)

Musfeldt, Janice

2012-02-01

Magnetoelectric coupling in materials like multiferroics, dilute magnetic semiconductors, and topological insulators has attracted a great deal of attention, although most work has been done in the static limit. Optical spectroscopy offers a way to investigate the dynamics of charge-spin coupling, an area where there has been much less effort. Using these techniques, we discovered that charge fluctuation in LuFe2O4, the prototypical charge ordered multiferroic, has an onset well below the charge ordering transition, supporting the ``order by fluctuation'' mechanism for the development of charge order superstructure. Bragg splitting and large magneto-optical contrast suggest a low temperature monoclinic distortion that can be driven by both temperature and magnetic field. At the same time, dramatic splitting of the LuO2 layer phonon mode is attributed to charge-rich/poor proximity effects, and its temperature dependence reveals the antipolar nature of the W layer pattern. Using optical techniques, we also discovered that α-Fe2O3, a chemically-similar parent compound and one of the world's oldest and most iconic antiferromagnetic materials, appears more red in applied magnetic field than in zero field conditions. This effect is driven by a field-induced reorientation of magnetic order. The oscillator strength lost in the color band is partially transferred to the magnon side band, a process that also reveals a new exciton pattern induced by the modified exchange coupling. Analysis of the exciton pattern exposes C2/c monoclinic symmetry in the high field phase of hematite. Taken together, these findings advance our understanding of iron-based materials under extreme conditions. [4pt] Collaborators include: X. S. Xu, P. Chen, Q. -C. Sun, T. V. Brinzari (Tennessee); S. McGill (NHMFL); J. De Groot, M. Angst, R. P. Hermann (Julich); A. D. Christianson, B. C. Sales, D. Mandrus (ORNL); A. P. Litvinchuk (Houston); J. -W. Kim (Ames); Z. Islam (Argonne); N. Lee, S. -W. Cheong (Rutgers).

Capturing 2D transient surface data of granular flows against obstacles with an RGB-D sensor

NASA Astrophysics Data System (ADS)

Caviedes-Voullieme, Daniel; Juez, Carmelo; Murillo, Javier; Garcia-Navarro, Pilar

2014-05-01

Landslides are an ubiquitous natural hazard, and therefore human infrastructure and settlements are often at risk in mountainous regions. In order to better understand and predict landslides, systematic studies of the phenomena need to be undertaken. In particular, computational tools which allow for analysis of field problems require to be thoroughly tested, calibrated and validated under controlled conditions. And to do so, it is necessary for such controlled experiments to be fully characterized in the same terms as the numerical model requires. This work presents an experimental study of dry granular flow over a rough bed with topography which resembles a mountain valley. It has an upper region with a very high slope. The geometry of the bed describes a fourth order polynomial curve, with a low point with zero slope, and afterwards a short region with adverse slope. Obstacles are present in the lower regions which are used as model geometries of human structures. The experiments consisted of a sudden release a mass of sand on the upper region, and allowing it to flow downslope. Furthermore, it has been frequent in previous studies to measure final states of the granular mass at rest, but seldom has transient data being provided, and never for the entire field. In this work we present transient measurements of the moving granular surfaces, obtained with a consumer-grade RGB-D sensor. The sensor, developed for the videogame industry, allows to measure the moving surface of the sand, thus obtaining elevation fields. The experimental results are very consistent and repeatable. The measured surfaces clearly show the distinctive features of the granular flow around the obstacles and allow to qualitatively describe the different flow patterns. More importantly, the quantitative description of the granular surface allows for benchmarking and calibration of predictive numerical models, key in scaling the small-scale experimental knowledge into the field.

77 FR 10584 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Sell Imbalance to bring the imbalance quantity as close to zero as possible. The Exchange proposes to... price to be obtained is not lower than the last sale if the last sale was a ``plus'' or ``zero plus... sale was a ``minus'' or ``zero minus'' tick. The purpose of a Sell Plus order is to ensure that a...

Zero Boil-OFF Tank Hardware Setup

NASA Image and Video Library

2017-09-19

iss053e027051 (Sept. 19, 2017) --- Flight Engineer Joe Acaba works in the U.S. Destiny laboratory module setting up hardware for the Zero Boil-Off Tank (ZBOT) experiment. ZBOT uses an experimental fluid to test active heat removal and forced jet mixing as alternative means for controlling tank pressure for volatile fluids. Rocket fuel, spacecraft heating and cooling systems, and sensitive scientific instruments rely on very cold cryogenic fluids. Heat from the environment around cryogenic tanks can cause their pressures to rise, which requires dumping or "boiling off" fluid to release the excess pressure, or actively cooling the tanks in some way.

Noninvasive blood-flow meter using a curved cannula with zero compensation for an axial flow blood pump.

PubMed

Kosaka, Ryo; Fukuda, Kyohei; Nishida, Masahiro; Maruyama, Osamu; Yamane, Takashi

2013-01-01

In order to monitor the condition of a patient using a left ventricular assist system (LVAS), blood flow should be measured. However, the reliable determination of blood-flow rate has not been established. The purpose of the present study is to develop a noninvasive blood-flow meter using a curved cannula with zero compensation for an axial flow blood pump. The flow meter uses the centrifugal force generated by the flow rate in the curved cannula. Two strain gauges served as sensors. The first gauges were attached to the curved area to measure static pressure and centrifugal force, and the second gauges were attached to straight area to measure static pressure. The flow rate was determined by the differences in output from the two gauges. The zero compensation was constructed based on the consideration that the flow rate could be estimated during the initial driving condition and the ventricular suction condition without using the flow meter. A mock circulation loop was constructed in order to evaluate the measurement performance of the developed flow meter with zero compensation. As a result, the zero compensation worked effectively for the initial calibration and the zero-drift of the measured flow rate. We confirmed that the developed flow meter using a curved cannula with zero compensation was able to accurately measure the flow rate continuously and noninvasively.

Developmental Increase in Kisspeptin-54 Release in Vivo Is Independent of the Pubertal Increase in Estradiol in Female Rhesus Monkeys (Macaca mulatta)

PubMed Central

Guerriero, Kathryn A.; Keen, Kim L.

2012-01-01

Kisspeptin (KP) signaling has been proposed as an important regulator in the mechanism of puberty. In this study, to determine the role of KP in puberty, we assessed the in vivo release pattern of KP-54 from the basal hypothalamus/stalk-median eminence in prepubertal and pubertal ovarian-intact female rhesus monkeys. We found that there was a developmental increase in mean KP-54 release, pulse frequency, and pulse amplitude, which is parallel to the developmental changes in GnRH release that we previously reported. Moreover, a nocturnal increase in KP-54 release becomes prominent after the onset of puberty. Because the pubertal increase in GnRH release occurs independent of the pubertal increase in circulating gonadal steroids, we further examined whether ovariectomy (OVX) modifies the release pattern of KP-54. Results show that OVX in pubertal monkeys enhanced mean KP-54 release and pulse amplitude but not pulse frequency, whereas OVX did not alter the release pattern of KP-54 in prepubertal monkeys. Estradiol replacement in OVX pubertal monkeys suppressed mean KP-54 release and pulse amplitude but not pulse frequency. Estradiol replacement in OVX prepubertal monkeys did not alter the KP-54 release pattern. Collectively these results suggest that the pubertal increase in KP release occurs independent of the pubertal increase in circulating estradiol. Nevertheless, the pubertal increase in KP release is not likely responsible for the initiation of the pubertal increase in GnRH release. Rather, after puberty onset, the increase in KP release contributes to further increase GnRH release during the progression of puberty. PMID:22315444

Two-nucleon S 0 1 amplitude zero in chiral effective field theory

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

Sanchez, M. Sanchez; Yang, C. -J.; Long, Bingwei

We present a new rearrangement of short-range interactions in the 1S 0 nucleon-nucleon channel within chiral effective field theory. This is intended to address the slow convergence of Weinberg’s scheme, which we attribute to its failure to reproduce the amplitude zero (scattering momentum ≃340 MeV) at leading order. After the power counting scheme is modified to accommodate the zero at leading order, it includes subleading corrections perturbatively in a way that is consistent with renormalization-group invariance. Systematic improvement is shown at next-to-leading order, and we obtain results that fit empirical phase shifts remarkably well all the way up to themore » pion-production threshold. As a result, an approach in which pions have been integrated out is included, which allows us to derive analytic results that also fit phenomenology surprisingly well.« less

Two-nucleon S 0 1 amplitude zero in chiral effective field theory

DOE PAGES

Sanchez, M. Sanchez; Yang, C. -J.; Long, Bingwei; ...

2018-02-05

We present a new rearrangement of short-range interactions in the 1S 0 nucleon-nucleon channel within chiral effective field theory. This is intended to address the slow convergence of Weinberg’s scheme, which we attribute to its failure to reproduce the amplitude zero (scattering momentum ≃340 MeV) at leading order. After the power counting scheme is modified to accommodate the zero at leading order, it includes subleading corrections perturbatively in a way that is consistent with renormalization-group invariance. Systematic improvement is shown at next-to-leading order, and we obtain results that fit empirical phase shifts remarkably well all the way up to themore » pion-production threshold. As a result, an approach in which pions have been integrated out is included, which allows us to derive analytic results that also fit phenomenology surprisingly well.« less

Catalytic Degradation of Dichlorvos Using Biosynthesized Zero Valent Iron Nanoparticles.

PubMed

Mehrotra, Neha; Tripathi, Ravi Mani; Zafar, Fahmina; Singh, Manoj Pratap

2017-06-01

The removal of dichlorvos contamination from water is a challenging task because of the presence of direct carbon to phosphorous covalent bond, which makes them resistant to chemical and thermal degradation. Although there have been reports in the literature for degradation of dichlorvos using nanomaterials, those are based on photocatalysis. In this paper, we report a simple and rapid method for catalytic degradation of dichlorvos using protein-capped zero valent iron nanoparticles (FeNPs). We have developed an unprecedented reliable, clean, nontoxic, eco-friendly, and cost-effective biological method for the synthesis of uniformly distributed FeNPs. Yeast extract was used as reducing and capping agent in the synthesis of FeNPs, and synthesized particles were characterized by the UV-visible spectroscopy, X -ray diffraction, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). TEM micrographs reveal that the nanoparticles size is distributed in the range of 2-10 nm. Selected area electron diffraction pattern shows the polycrystalline rings of FeNPs. The mean size was found to be 5.006 nm from ImageJ. FTIR spectra depicted the presence of biomolecules, which participated in the synthesis and stabilization of nanoparticles. As synthesized, FeNPs were used for the catalytic degradation of dichlorvos in aqueous medium. The degradation activity of the FeNPs has been investigated by the means of incubation time effect, oxidant effect, and nanoparticle concentration effect. The ammonium molybdate test was used to confirm the release of phosphate ions during the interaction of dichlorvos with FeNPs.

Steady bound electromagnetic eigenstate arises in a homogeneous isotropic linear metamaterial with zero-real-part-of-impedance and nonzero-imaginary-part-of-wave-vector

NASA Astrophysics Data System (ADS)

Chen, Jiangwei; Dai, Yuyao; Yan, Lin; Zhao, Huimin

2018-04-01

In this paper, we shall demonstrate theoretically that steady bound electromagnetic eigenstate can arise in an infinite homogeneous isotropic linear metamaterial with zero-real-part-of-impedance and nonzero-imaginary-part-of-wave-vector, which is partly attributed to that, here, nonzero-imaginary-part-of-wave-vector is not involved with energy losses or gain. Altering value of real-part-of-impedance of the metamaterial, the bound electromagnetic eigenstate may become to be a progressive wave. Our work may be useful to further understand energy conversion and conservation properties of electromagnetic wave in the dispersive and absorptive medium and provides a feasible route to stop, store and release electromagnetic wave (light) conveniently by using metamaterial with near-zero-real-part-of-impedance.

A conformal mapping based fractional order approach for sub-optimal tuning of PID controllers with guaranteed dominant pole placement

NASA Astrophysics Data System (ADS)

Saha, Suman; Das, Saptarshi; Das, Shantanu; Gupta, Amitava

2012-09-01

A novel conformal mapping based fractional order (FO) methodology is developed in this paper for tuning existing classical (Integer Order) Proportional Integral Derivative (PID) controllers especially for sluggish and oscillatory second order systems. The conventional pole placement tuning via Linear Quadratic Regulator (LQR) method is extended for open loop oscillatory systems as well. The locations of the open loop zeros of a fractional order PID (FOPID or PIλDμ) controller have been approximated in this paper vis-à-vis a LQR tuned conventional integer order PID controller, to achieve equivalent integer order PID control system. This approach eases the implementation of analog/digital realization of a FOPID controller with its integer order counterpart along with the advantages of fractional order controller preserved. It is shown here in the paper that decrease in the integro-differential operators of the FOPID/PIλDμ controller pushes the open loop zeros of the equivalent PID controller towards greater damping regions which gives a trajectory of the controller zeros and dominant closed loop poles. This trajectory is termed as "M-curve". This phenomena is used to design a two-stage tuning algorithm which reduces the existing PID controller's effort in a significant manner compared to that with a single stage LQR based pole placement method at a desired closed loop damping and frequency.

On-Orbit Performance of the TRMM Mission Mode

NASA Technical Reports Server (NTRS)

Robertson, Brent; Placanica, Sam; Morgenstern, Wendy; Hashmall, Joseph A.; Glickman, Jonathan; Natanson, Gregory

1999-01-01

This paper presents an overview of the Tropical Rainfall Measuring Mission (TRMM) Attitude Control System along with detailed in-flight performance results of the TRMM Mission mode. The TRMM spacecraft is an Earth-pointed, zero momentum bias satellite launched on November 27, 1997 from Tanegashima Space Center, Japan. TRMM is a joint mission between NASA and the National Space Development Agency of Japan designed to monitor and study tropical rainfall and the associated release of energy. Prior to calibration, the spacecraft attitude showed larger Sun sensor yaw updates than expected. This was traced to not just sensor misalignment but also to a misalignment between the two heads within each Sun sensor. In order to avoid alteration of the flight software, Sun sensor transfer function coefficients were determined to minimize the error due to head misalignment. This paper describes the design, on-orbit checkout, calibration and performance of the TRMM Mission Mode with respect to the mission level requirements.

CFD modeling of two-stage ignition in a rapid compression machine: Assessment of zero-dimensional approach

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

Mittal, Gaurav; Raju, Mandhapati P.; Sung, Chih-Jen

2010-07-15

In modeling rapid compression machine (RCM) experiments, zero-dimensional approach is commonly used along with an associated heat loss model. The adequacy of such approach has not been validated for hydrocarbon fuels. The existence of multi-dimensional effects inside an RCM due to the boundary layer, roll-up vortex, non-uniform heat release, and piston crevice could result in deviation from the zero-dimensional assumption, particularly for hydrocarbons exhibiting two-stage ignition and strong thermokinetic interactions. The objective of this investigation is to assess the adequacy of zero-dimensional approach in modeling RCM experiments under conditions of two-stage ignition and negative temperature coefficient (NTC) response. Computational fluidmore » dynamics simulations are conducted for n-heptane ignition in an RCM and the validity of zero-dimensional approach is assessed through comparisons over the entire NTC region. Results show that the zero-dimensional model based on the approach of 'adiabatic volume expansion' performs very well in adequately predicting the first-stage ignition delays, although quantitative discrepancy for the prediction of the total ignition delays and pressure rise in the first-stage ignition is noted even when the roll-up vortex is suppressed and a well-defined homogeneous core is retained within an RCM. Furthermore, the discrepancy is pressure dependent and decreases as compressed pressure is increased. Also, as ignition response becomes single-stage at higher compressed temperatures, discrepancy from the zero-dimensional simulations reduces. Despite of some quantitative discrepancy, the zero-dimensional modeling approach is deemed satisfactory from the viewpoint of the ignition delay simulation. (author)« less

77 FR 10581 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... quantity as close to zero as possible. The Exchange proposes to amend Rule 123C(4)(a)(vi) to add that LOC... ``plus'' or ``zero plus'' tick, and is not lower than the last sale plus the minimal fractional change in the stock if the last sale was a ``minus'' or ``zero minus'' tick. The purpose of a Sell Plus order is...

Zero-gravity open-type urine receptacle

NASA Technical Reports Server (NTRS)

Girala, A. S.

1972-01-01

The development of the zero-gravity open-type urine receptacle used in the Apollo command module is described. This type receptacle eliminates the need for a cuff-type urine collector or for the penis to circumferentially contact the receptacle in order to urinate. This device may be used in a gravity environment, varying from zero gravity to earth gravity, such as may be experienced in a space station or space base.

An Active Z Gravity Compensation System

DTIC Science & Technology

1992-07-01

is necessary to convert the modified digital controller back into continuous time, assuming a zero -order hold for output, and using the Padd ...most likely higher frequency pole- zero pairs introduced by the motor and torque servo, these are generally non-oscillatory, and small in amplitude...on the output of the PI control. The detection scheme is the following: if the output of the fuzzy controller has remained zero (static system) for

Patterns and Oscillations in Reaction-Diffusion Systems with Intrinsic Fluctuations

NASA Astrophysics Data System (ADS)

Giver, Michael; Goldstein, Daniel; Chakraborty, Bulbul

2013-03-01

Intrinsic or demographic noise has been shown to play an important role in the dynamics of a variety of systems including predator-prey populations, biochemical reactions within cells, and oscillatory chemical reaction systems, and is known to give rise to oscillations and pattern formation well outside the parameter range predicted by standard mean-field analysis. Initially motivated by an experimental model of cells and tissues where the cells are represented by chemical reagents isolated in emulsion droplets, we study the stochastic Brusselator, a simple activator-inhibitor chemical reaction model. Our work extends the results of recent studies on the zero and one dimensional systems with the ultimate goals of understanding the role of noise in spatially structured systems and engineering novel patterns and attractors induced by fluctuations. In the zero dimensional system, we observe a noise induced switching between small and large amplitude oscillations when a separation of time scales is present, while the spatially extended system displays a similar switching between a stationary Turing pattern and uniform oscillations.

Nitrogen release from urea with different coatings.

PubMed

Campos, Odirley R; Mattiello, Edson Marcio; Cantarutti, Reinaldo Bertola; Vergütz, Leonardus

2018-01-01

Coatings or urease inhibitors are designed to reduce losses of ammonia [NH 3(g) ] from urea fertilizers. However, nitrogen (N) release and its effects on soil solution have not previously been evaluated under standardized conditions in soils. In this study, the urea fertilizers were incubated in chambers filled with sandy loam soil, adapted for the collection of NH 3(g) and soil solution by centrifugation. In the fast-release N fertilizers, around 93% and 100% of urea-N applied was recovered within the first hours of incubation. In contrast, in the slow-release N fertilizers, less than 40% of urea-N applied, was recovered at 19 days of incubation. The maximum N release from the fertilizers followed the order: UP1 (106%) ≈ UNBPT (102%) ≈ urea (93%) > USP2 (57%) ≈ USP3 (57%) > USP4 (31%) ≈ USP5 (18%). NH 3(g) volatilization accounted for only 3% of the applied N in the slow-release fertilizers, which corresponded to about 88% less than the NH 3(g) loss from prilled urea. This study demonstrated distinct N release patterns, which changed the N dynamics in the soil. Some coatings effectively delayed urea release from granules and reduced NH 3(g) gas losses, while other were not efficient. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

39 CFR 762.28 - Release of original disbursement postal money orders.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Release of original disbursement postal money... and Processing of Disbursement Postal Money Orders § 762.28 Release of original disbursement postal money orders. An original Disbursement Postal Money Order may be released to a responsible endorser only...

Design for the optical retardation in broadband zero-order half-wave plates.

PubMed

Liu, Jin; Cai, Yi; Chen, Hongyi; Zeng, Xuanke; Zou, Da; Xu, Shixiang

2011-04-25

This paper presents a novel design for broadband zero-order half-wave plates to eliminate the first-order or up to second-order wavelength-dependent birefringent phase retardation (BPR) with 2 or 3 different birefringent materials. The residual BPRs of the plates increase monotonously with the wavelength deviation from a selected wavelength, so the plates are applicable to the broadband light pulses which gather most of the light energy around their central wavelengths. The model chooses the materials by the birefringent dispersion coefficient and evaluates the performances of the plates by the weighted average of the absolute value of residual BPR in order to emphasize the contributions of the incident spectral components whose possess higher energies.

AMELIORATION OF ACID MINE DRAINAGE USING REACTIVE MIXTURES IN PERMEABLE REACTIVE BARRIERS

EPA Science Inventory

The generation and release of acidic drainage from mine wastes is an environmental problem of international scale. The use of zero-valent iron and/or iron mixtures in subsurface Permeable Reactive Barriers (PRB) presents a possible passive alternative for remediating acidic grou...

Auger electron diffraction study of V/Fe(100) interface formation

NASA Astrophysics Data System (ADS)

Huttel, Y.; Avila, J.; Asensio, M. C.; Bencok, P.; Richter, C.; Ilakovac, V.; Heckmann, O.; Hricovini, K.

1998-05-01

Vanadium atoms present a magnetic moment different to zero when they are part of a thin film deposited on Fe or as a bimetallic Fe-V alloy. The understanding of this phenomenon can only be achieved with a correct structural description of these types of systems. We report an Auger electron diffraction investigation of V films grown on body cubic centred (b.c.c.) Fe(100) substrates. Angular-scanned Auger electron diffraction (AED) patterns of V L 23M 23M 4 (473 eV) and Fe L 3VV (703 eV) show the formation of a well-ordered V/Fe interface even at room temperature. The AED patterns of V films in the range of vanadium submonolayer provide evidence of an isotropic Auger emission, indicating the absence of interdiffusion of V atoms into the Fe substrate and absence of cluster growth of the V film. The annealing of these films up to 400°C does not activate the substitution of the topmost Fe surface layers by V atoms.

5 CFR 351.601 - Order of release from competitive level.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Order of release from competitive level... REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.601 Order of release from competitive level. (a) Each agency must select competing employees for release from a competitive level (including...

5 CFR 351.601 - Order of release from competitive level.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Order of release from competitive level... REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.601 Order of release from competitive level. (a) Each agency must select competing employees for release from a competitive level (including...

Calibration of the photometric G passband for Gaia Data Release 1

NASA Astrophysics Data System (ADS)

Maíz Apellániz, J.

2017-12-01

Context. On September 2016 the first data from Gaia were released (DR1). The first release included photometry for over 109 sources in the very broad G system. Aims: The aims here are to test the correspondence between G magnitudes in DR1 and the synthetic equivalents derived using spectral energy distributions from observed and model spectrophotometry; to correct the G passband curve; and to measure the zero point in the Vega system. Methods: I have computed the synthetic G and Tycho-2 BTVT photometry for a sample of stars using the Next Generation Spectral Library (NGSL) and the Hubble Space Telescope (HST) CALSPEC spectroscopic standards. Results: I have found that the nominal G passband curve is too blue for the DR1 photometry, as shown by the presence of a color term in the comparison between observed and synthetic magnitudes. A correction to the passband applying a power law in λ with an exponent of 0.783 eliminates the color term. The corrected passband has a Vega zero point of 0.070 ± 0.004 mag. Tables 1 and 2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/608/L8

Floating lipid beads for the improvement of bioavailability of poorly soluble basic drugs: in-vitro optimization and in-vivo performance in humans.

PubMed

Abouelatta, Samar M; Aboelwafa, Ahmed A; Khalil, Rawia M; ElGazayerly, Omaima N

2015-01-01

The challenge in developing oral drug delivery systems of poorly soluble basic drugs is primarily due to their pH dependent solubility. Cinnarizine (CNZ), a model for a poorly soluble basic drug, has pH dependent solubility; where it dissolves readily at low pH in the stomach and exhibits a very low solubility at pH values greater than 4. It is also characterized by a short half life of 3-6h, which requires frequent daily administration resulting in poor patient compliance. In an attempt to solve these problems, extended release floating lipid beads were formulated. A 2(4) full factorial design was utilized for optimization of the effects of various independent variables; lipid:drug ratio, % Pluronic F-127, % Sterotex, and Gelucire 43/01:Gelucire 50/13 ratio, on the loading efficiency and release of CNZ from the lipid beads. In-vivo pharmacokinetic study of the optimized CNZ-lipid beads compared to Stugeron® (reference standard) was performed in healthy human volunteers. A promising approach for enhancing the bioavailability of the poorly soluble basic drug, CNZ, utilizing novel and simple floating lipid beads was successfully developed. Zero order release profile of CNZ was achieved for 12h. Mean AUC0-24 and AUC0-∞ of the optimized CNZ-loaded lipid beads were 4.23 and 6.04 times that of Stugeron® tablets respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Microstructure from ferroelastic transitions using strain pseudospin clock models in two and three dimensions: A local mean-field analysis

NASA Astrophysics Data System (ADS)

Vasseur, Romain; Lookman, Turab; Shenoy, Subodh R.

2010-09-01

We show how microstructure can arise in first-order ferroelastic structural transitions, in two and three spatial dimensions, through a local mean-field approximation of their pseudospin Hamiltonians, that include anisotropic elastic interactions. Such transitions have symmetry-selected physical strains as their NOP -component order parameters, with Landau free energies that have a single zero-strain “austenite” minimum at high temperatures, and spontaneous-strain “martensite” minima of NV structural variants at low temperatures. The total free energy also has gradient terms, and power-law anisotropic effective interactions, induced by “no-dislocation” St Venant compatibility constraints. In a reduced description, the strains at Landau minima induce temperature dependent, clocklike ZNV+1 Hamiltonians, with NOP -component strain-pseudospin vectors S⃗ pointing to NV+1 discrete values (including zero). We study elastic texturing in five such first-order structural transitions through a local mean-field approximation of their pseudospin Hamiltonians, that include the power-law interactions. As a prototype, we consider the two-variant square/rectangle transition, with a one-component pseudospin taking NV+1=3 values of S=0,±1 , as in a generalized Blume-Capel model. We then consider transitions with two-component (NOP=2) pseudospins: the equilateral to centered rectangle (NV=3) ; the square to oblique polygon (NV=4) ; the triangle to oblique (NV=6) transitions; and finally the three-dimensional (3D) cubic to tetragonal transition (NV=3) . The local mean-field solutions in two-dimensional and 3D yield oriented domain-wall patterns as from continuous-variable strain dynamics, showing the discrete-variable models capture the essential ferroelastic texturings. Other related Hamiltonians illustrate that structural transitions in materials science can be the source of interesting spin models in statistical mechanics.

Photonic zero mode in a non-Hermitian photonic lattice.

PubMed

Pan, Mingsen; Zhao, Han; Miao, Pei; Longhi, Stefano; Feng, Liang

2018-04-03

Zero-energy particles (such as Majorana fermions) are newly predicted quasiparticles and are expected to play an important role in fault-tolerant quantum computation. In conventional Hermitian quantum systems, however, such zero states are vulnerable and even become vanishing if couplings with surroundings are of the same topological nature. Here we demonstrate a robust photonic zero mode sustained by a spatial non-Hermitian phase transition in a parity-time (PT) symmetric lattice, despite the same topological order across the entire system. The non-Hermitian-enhanced topological protection ensures the reemergence of the zero mode at the phase transition interface when the two semi-lattices under different PT phases are decoupled effectively in their real spectra. Residing at the midgap level of the PT symmetric spectrum, the zero mode is topologically protected against topological disorder. We experimentally validated the robustness of the zero-energy mode by ultrafast heterodyne measurements of light transport dynamics in a silicon waveguide lattice.

Nonlinear dynamics of the rock-paper-scissors game with mutations.

PubMed

Toupo, Danielle F P; Strogatz, Steven H

2015-05-01

We analyze the replicator-mutator equations for the rock-paper-scissors game. Various graph-theoretic patterns of mutation are considered, ranging from a single unidirectional mutation pathway between two of the species, to global bidirectional mutation among all the species. Our main result is that the coexistence state, in which all three species exist in equilibrium, can be destabilized by arbitrarily small mutation rates. After it loses stability, the coexistence state gives birth to a stable limit cycle solution created in a supercritical Hopf bifurcation. This attracting periodic solution exists for all the mutation patterns considered, and persists arbitrarily close to the limit of zero mutation rate and a zero-sum game.

Synthesis, Characterization, and Sensitivity Analysis of Urea Nitrate (UN)

DTIC Science & Technology

2015-04-01

of the line is the rate of the reaction for the corresponding temperature. The equations for the zero order reaction and half- life equation follow...rate law (k is rate constant; [A] is the concentration of UN) Rate = k[A]n . (1) Eq. 2 shows the half-life (t½) equation for a zero order reaction...MGMT 1 GOVT PRINTG OFC (PDF) A MALHOTRA 2 WEAPONS DEV & (PDF) INTEGRATION DIRCTRT AMRDEC RDMR WDN J NEIDERT G DRAKE

Mechanically metastable structures generated by single pulse laser-induced periodic surface structures (LIPSS) in the photoresist SU8.

PubMed

Reinhardt, Hendrik; Peschke, Patrick; Riedel, René; Hampp, Norbert

2018-07-27

Laser-induced periodic surface structures (LIPSS) with a periodicity of 351 nm are generated in the negative photoresist SU8 by single nanosecond laser pulse impact. Friction scans indicate the periodic pattern to comprise alternating regions of crosslinked and non-crosslinked SU8. Intriguingly, even minor mechanical stimuli in the order of nanonewtons cause the unfolding or rather the deletion of the characteristic periodic pattern similarly to the release of a pre-loaded spring. This feature combined with high resilience to heat and photon irradiation makes SU8-LIPSS attractive for applications such as mechanical stress monitors, self-destructing memory and passive micro actuators.

Mechanically metastable structures generated by single pulse laser-induced periodic surface structures (LIPSS) in the photoresist SU8

NASA Astrophysics Data System (ADS)

Reinhardt, Hendrik; Peschke, Patrick; Riedel, René; Hampp, Norbert

2018-07-01

Laser-induced periodic surface structures (LIPSS) with a periodicity of 351 nm are generated in the negative photoresist SU8 by single nanosecond laser pulse impact. Friction scans indicate the periodic pattern to comprise alternating regions of crosslinked and non-crosslinked SU8. Intriguingly, even minor mechanical stimuli in the order of nanonewtons cause the unfolding or rather the deletion of the characteristic periodic pattern similarly to the release of a pre-loaded spring. This feature combined with high resilience to heat and photon irradiation makes SU8-LIPSS attractive for applications such as mechanical stress monitors, self-destructing memory and passive micro actuators.

Optimal Control Surface Layout for an Aeroservoelastic Wingbox

NASA Technical Reports Server (NTRS)

Stanford, Bret K.

2017-01-01

This paper demonstrates a technique for locating the optimal control surface layout of an aeroservoelastic Common Research Model wingbox, in the context of maneuver load alleviation and active utter suppression. The combinatorial actuator layout design is solved using ideas borrowed from topology optimization, where the effectiveness of a given control surface is tied to a layout design variable, which varies from zero (the actuator is removed) to one (the actuator is retained). These layout design variables are optimized concurrently with a large number of structural wingbox sizing variables and control surface actuation variables, in order to minimize the sum of structural weight and actuator weight. Results are presented that demonstrate interdependencies between structural sizing patterns and optimal control surface layouts, for both static and dynamic aeroelastic physics.

Transverse circular-polarized Bessel beam generation by inward cylindrical aperture distribution.

PubMed

Pavone, S C; Ettorre, M; Casaletti, M; Albani, M

2016-05-16

In this paper the focusing capability of a radiating aperture implementing an inward cylindrical traveling wave tangential electric field distribution directed along a fixed polarization unit vector is investigated. In particular, it is shown that such an aperture distribution generates a non-diffractive Bessel beam whose transverse component (with respect to the normal of the radiating aperture) of the electric field takes the form of a zero-th order Bessel function. As a practical implementation of the theoretical analysis, a circular-polarized Bessel beam launcher, made by a radial parallel plate waveguide loaded with several slot pairs, arranged on a spiral pattern, is designed and optimized. The proposed launcher performance agrees with the theoretical model and exhibits an excellent polarization purity.

Chiral symmetry restoration at finite temperature and chemical potential in the improved ladder approximation

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

Taniguchi, Y.; Yoshida, Y.

1997-02-01

The chiral symmetry of QCD is studied at finite temperature and chemical potential using the Schwinger-Dyson equation in the improved ladder approximation. We calculate three order parameters: the vacuum expectation value of the quark bilinear operator, the pion decay constant, and the quark mass gap. We have a second order phase transition at the temperature T{sub c}=169 MeV along the zero chemical potential line, and a first order phase transition at the chemical potential {mu}{sub c}=598 MeV along the zero temperature line. We also calculate the critical exponents of the three order parameters. {copyright} {ital 1997} {ital The American Physicalmore » Society}« less

Quantitative Analysis of Clopidogrel Bisulphate and Aspirin by First Derivative Spectrophotometric Method in Tablets

PubMed Central

Game, Madhuri D.; Gabhane, K. B.; Sakarkar, D. M.

2010-01-01

A simple, accurate and precise spectrophotometric method has been developed for simultaneous estimation of clopidogrel bisulphate and aspirin by employing first order derivative zero crossing method. The first order derivative absorption at 232.5 nm (zero cross point of aspirin) was used for clopidogrel bisulphate and 211.3 nm (zero cross point of clopidogrel bisulphate) for aspirin.Both the drugs obeyed linearity in the concentration range of 5.0 μg/ml to 25.0 μg/ml (correlation coefficient r2<1). No interference was found between both determined constituents and those of matrix. The method was validated statistically and recovery studies were carried out to confirm the accuracy of the method. PMID:21969765

Time delay of critical images in the vicinity of cusp point of gravitational-lens systems

NASA Astrophysics Data System (ADS)

Alexandrov, A.; Zhdanov, V.

2016-12-01

We consider approximate analytical formulas for time-delays of critical images of a point source in the neighborhood of a cusp-caustic. We discuss zero, first and second approximations in powers of a parameter that defines the proximity of the source to the cusp. These formulas link the time delay with characteristics of the lens potential. The formula of zero approximation was obtained by Congdon, Keeton & Nordgren (MNRAS, 2008). In case of a general lens potential we derived first order correction thereto. If the potential is symmetric with respect to the cusp axis, then this correction is identically equal to zero. For this case, we obtained second order correction. The relations found are illustrated by a simple model example.

Formulation and in vitro evaluation of Hydrodynamically balanced system for theophylline delivery.

PubMed

Nayak, Amit Kumar; Malakar, Jadupati

2011-06-01

The objective of the present study was to formulate hydrodynamically balanced systems (HBSs) of theophylline as single unit capsules. They were formulated by physical blending of theophylline with hydroxypropyl methyl cellulose, polyethylene oxide, polyvinyl pyrrolidone, ethyl cellulose, liquid paraffin, and lactose in different ratios. These theophylline HBS capsules were evaluated for weight uniformity, drug content uniformity, in vitro floating behavior and drug release in simulated gastric fluids (pH 1.2). All these formulated HBS capsules containing theophylline were floated well over 6 hours with no floating lag time, and also showed sustained in vitro drug release in simulated gastric fluid over 6 hours. The theophylline release from these capsules was more sustained with the addition of release modifiers (ethyl cellulose and liquid paraffin). The drug release pattern from these capsules was correlated well with first order model (F-1 to F-5) and Korsmeyer-Peppas model (F-6 and F-7) with the non-Fickian (anomalous) diffusion mechanism. These experimental results clearly indicated that these theophylline HBS capsules were able to remain buoyant in the gastric juice for longer period, which may improve oral bioavailability of theophylline.

Revisiting the BaO2/BaO redox cycle for solar thermochemical energy storage.

PubMed

Carrillo, A J; Sastre, D; Serrano, D P; Pizarro, P; Coronado, J M

2016-03-21

The barium peroxide-based redox cycle was proposed in the late 1970s as a thermochemical energy storage system. Since then, very little attention has been paid to such redox couples. In this paper, we have revisited the use of reduction-oxidation reactions of the BaO2/BaO system for thermochemical heat storage at high temperatures. Using thermogravimetric analysis, reduction and oxidation reactions were studied in order to find the main limitations associated with each process. Furthermore, the system was evaluated through several charge-discharge stages in order to analyse its possible degradation after repeated cycling. Through differential scanning calorimetry the heat stored and released were also determined. Oxidation reaction, which was found to be slower than reduction, was studied in more detail using isothermal tests. It was observed that the rate-controlling step of BaO oxidation follows zero-order kinetics, although at high temperatures a deviation from Arrhenius behaviour was observed probably due to hindrances to anionic oxygen diffusion caused by the formation of an external layer of BaO2. This redox couple was able to withstand several redox cycles without deactivation, showing reaction conversions close to 100% provided that impurities are previously eliminated through thermal pre-treatment, demonstrating the feasibility of this system for solar thermochemical heat storage.

Water-based preparation of spider silk films as drug delivery matrices.

PubMed

Agostini, Elisa; Winter, Gerhard; Engert, Julia

2015-09-10

The main focus of this work was to obtain a drug delivery matrix characterized by biocompatibility, water insolubility and good mechanical properties. Moreover the preparation process has to be compatible with protein encapsulation and the obtained matrix should be able to sustain release a model protein. Spider silk proteins represent exceptional natural polymers due to their mechanical properties in combination with biocompatibility. As both hydrophobic and slowly biodegrading biopolymers, recombinant spider silk proteins fulfill the required properties for a drug delivery system. In this work, we present the preparation of eADF4(C16) films as drug delivery matrices without the use of any organic solvent. Water-based spider silk films were characterized in terms of protein secondary structure, thermal stability, zeta-potential, solubility, mechanical properties, and water absorption and desorption. Additionally, this study includes an evaluation of their application as a drug delivery system for both small molecular weight drugs and high molecular weight molecules such as proteins. Our investigation focused on possible improvements in the film's mechanical properties including plasticizers in the film matrix. Furthermore, different film designs were prepared, such as: monolayer, coated monolayer, multilayer (sandwich), and coated multilayer. The release of the model protein BSA from these new systems was studied. Results indicated that spider silk films are a promising protein drug delivery matrix, capable of releasing the model protein over 90 days with a release profile close to zero order kinetic. Such films could be used for several pharmaceutical and medical purposes, especially when mechanical strength of a drug eluting matrix is of high importance. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro and in vivo evaluation of an oral sustained release hepatoprotective caffeine loaded w/o Pickering emulsion formula - containing wheat germ oil and stabilized by magnesium oxide nanoparticles.

PubMed

Elmotasem, Heba; Farag, Hala K; Salama, Abeer A A

2018-05-16

The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects. The MgO NPs were prepared via sol-gel method, and then were characterized using X-ray diffractometry, transmission electron microscopy, contact angle and cytotoxicity. The Pickering emulsion formula stabilized by MgO NPs (F1) was compared to another stabilized by conventional MgO particles (F2). Both were evaluated regarding droplet size, stability and caffeine release. F1 was stable against phase separation for a 2 months period. Its droplets mean size was 665.9 ± 90 nm. F1 afforded sustained release for caffeine that reached 70% within 48 h that followed zero order kinetics. 100 ppm of F1 showed nearly 36% growth inhibition of hepatocellular carcinoma (HEPG2). In vivo and histopathalogical evaluations were conducted on CCl 4 intoxicated rats. Biochemical analysis for liver enzymes - (ALT and AST), oxidative stress biomarkers and the inflammation marker (protein kinase C) - revealed that the selected formula elicited significant hepatoprotection. This formula acted as an economical approach to multiple therapy and afforded safe effective sustained level for caffeine. Copyright © 2018. Published by Elsevier B.V.

Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of Mentha piperita oil.

PubMed

Sibanda, Wilbert; Pillay, Viness; Danckwerts, Michael P; Viljoen, Alvaro M; van Vuuren, Sandy; Khan, Riaz A

2004-03-12

A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginate-pectinate oilisphere complex as a potential system for the in vitro site-specific release of Mentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%-1.5% wt/vol), crosslinkers (0%-4% wt/vol), and crosslinking reaction times (0.5-6 hours) (independent variables). Particle size analysis indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from 6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the total fracture energy was the most suitable optimization objective (R2 = 0.88, Durbin-Watson Index = 1.21%, Coefficient of Variation (CV) = 33.21%). The Lagrangian technique produced no significant differences (P > .05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks, as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network epoch approximately 0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n > 0.99), whereby analysis of release data indicated that diffusion (Fickian constant k1 = 0.74 vs relaxation constant k2 = 0.02) was the predominant release mechanism.

Comparative evaluation of single and bilayered lamotrigine floating tablets

PubMed Central

Lakshmi, PK; Sridhar, M; Shruthi, B

2013-01-01

Aim: The purpose of this study was to prepare lamotrigine (LM) bilayered and single layered floating tablets and to compare their release profiles. Materials and Methods: LM floating tablets were prepared by direct compression method. Drug, hydroxy propyl methyl cellulose K4M, lactose monohydrate and polyvinylpyrrolidone K30 constitute controlled release layer components and floating layer components includes polymers and sodium bicarbonate. The prepared tablets were evaluated for physicochemical parameters such as hardness, friability, weight variation, thickness, floating lag time (FLT), floating time, in vitro buoyancy study, in vitro release studies. The drug-polymer interaction was studied by fourier transform infrared and differential scanning calorimetry. Results and Discussion: The FLT of all the formulations were within the prescribed limits (<3 min). When ethyl cellulose was used as floating layer component, tablets showed good buoyancy effect but eroded within 6-8 h. Hence it was replaced with hydroxypropyl cellulose -M hydrophilic polymer, which showed good FLT and floating duration for 16 h. Formulation LFC4 was found to be optimized with dissolution profile of zero order kinetics showing fickian diffusion. A comparative study of bilayered and single layered tablets of LM showed a highest similarity factor of 83.03, difference factor of 2.74 and t-test (P < 0.05) indicates that there is no significant difference between them. Conclusion: Though bilayered tablet possess many advantages, single layered tablet would be economical, cost-effective and reproducible for large scale production in the industry. However, the results of present study demonstrated that the in vitro development of bilayered gastro retentive floating tablets with controlled drug release profile for LM is feasible. PMID:24167788

Uptake mechanism of furosemide-loaded pegylated nanoparticles by cochlear cell lines.

PubMed

Youm, Ibrahima; Youan, Bi-Botti C

2013-10-01

This study tests the hypothesis that pegylated nanoparticles (NPs) could be taken up by the cochlear cells [House Ear Institute-organ of Corti 1 (HEI-OC1) and Stria vascularis K-1 (SVK-1)], through endocytic pathways. Furthermore, the in vitro drug release and the cytotoxicity of Furosemide (FUR)-loaded NPs on these two cochlear cells are investigated. FUR-loaded pegylated NPs are prepared by the emulsion-solvent diffusion method without surfactant. The NPs are characterized for particle mean diameter, polydispersity index (PDI), morphology, percent drug encapsulation efficiency (EE%), and FUR release kinetics. The methyl tetrazolium salt (MTS) and lactate dehydrogenase (LDH) bioassays are used to evaluate in vitro, the cytotoxicity of FUR-loaded NPs and native FUR. The NPs uptake is investigated using confocal microscopy, microplate reader/fluorimetry, and flow cytometry. Spherical NPs with a mean diameter range of 133-210 nm and PDI values varying from 0.037 to 0.41 are produced. The FUR EE% is 86% and the drug is released from the NPs according to the zero-order and Higuchi models. After treatment with blank NPs, the percentage of cell viability and cell death are 95.96% and 8.95%, in HEI-OC1 cells, respectively. The NPs are internalized by HEI-OC1 cells through a clathrin-dependent pathway. In addition, results show that NPs can be taken up via clathrin and cytoskeleton mediated pathways in SVK-1 cells. The internalization of the pegylated NPs can enhance the drug toxicity by necrosis in a dose-dependent and sustained release manner. The formulated NPs provide a promising template for a targeted drug delivery system to the inner ear. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers.

PubMed

Reddy, Arun B; Reddy, Narendar D

2017-07-01

Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC K 4 M and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.

Millimeter-wave integrated-horn antennas. I - Theory. II - Experiment

NASA Technical Reports Server (NTRS)

Eleftheriades, George V.; Ali-Ahmad, Walid Y.; Katehi, Linda P. B.; Rebeiz, Gabriel M.

1991-01-01

Full-wave analysis is employed to determine the far-field pattern and input impedance of a dipole-fed horn antenna in a ground plane, and the theoretical results are compared with mm-wave and microwave data. The theoretical work exploits the Green's function corresponding to the horn structure and the method of moments. It is determined that the horn should have 70 sections/wavelength and 50 secondary modes for optimized accuracy, and certain dipole positions can reduce the resonance to zero. The experimentally derived impedance and radiation patterns agree with the constraints developed theoretically. The 70-degree flare-angle horn with selected dipole positions and horn apertures yields good radiation patterns, cross-polarization levels, and resonant dipole impedances. The conclusions are of interest to the development of the horn antennas etched in Si/GaAs for applications to zero-visibility tracking, radio astronomy, plasma diagnostics, and remote sensing.

LABORATORY EVALUATION OF ZERO-VALENT IRON TO TREAT GROUNDWATER IMPACTED BY ACID MINE DRAINAGE

EPA Science Inventory

The generation and release of acidic, metal-rich water from mine wastes continues to be an intractable environmental problem. Although the effects of acid mine drainage (AMD) are most evident in surface waters, there is an obvious need for developing cost-effective approaches fo...

Disease registries on the nationwide health information network.

PubMed

Russler, Daniel

2011-05-01

Donation by individuals of their protected health information (PHI) for evidence-based research potentially benefits all individuals with disease through improved understandings of disease patterns. In the future, a better understanding of how disease features combine into unique patterns of disease will generate new disease classifications, supporting greater specificity in health management techniques. However, without large numbers of people who donate their PHI to disease registries designed for research, it is difficult for researchers to discover the existence of complex patterns or to create more specific evidence-based management techniques. In order to identify new opportunities in disease registry design, an analysis of the current stage of maturity of the newly created U.S. Nationwide Health Information Network (NwHIN) related to large-scale consumer donation of PHI is presented. Utilizing a use-case analysis methodology, the consumer-centric designs of the policies and technologies created for the NwHIN were examined for the potential to support consumer donations of PHI to research. The NwHIN design has placed the enforcement point for the policy-based release of PHI over the Internet into a specialized gateway accessible to consumer authorization. However, current NwHIN policies leave the final decision regarding release of PHI for research to the health care providers rather than to the consumers themselves. Should disease registries designed for research be established on the NwHIN, consumers might then directly authorize the donation of their PHI to these disease registries. However, under current NwHIN policies, consumer authorization does not guarantee release of PHI by health providers. © 2011 Diabetes Technology Society.

Study of optical reflectance properties in 1D annular photonic crystal containing double negative (DNG) metamaterials

NASA Astrophysics Data System (ADS)

Srivastava, Sanjeev K.; Aghajamali, Alireza

2016-05-01

Theoretical investigation of photonic band gaps or reflection bands in one-dimensional annular photonic crystal (APC) containing double negative (DNG) metamaterials and air has been presented. The proposed structure consists of the alternate layers of dispersive DNG material and air immersed in free space. In order to study photonic band gaps we obtain the reflectance spectrum of the annular PC by employing the transfer matrix method (TMM) in the cylindrical waves for both TE and TM polarizations. In this work we study the effect of azimuthal mode number (m) and starting radius (ρ0) on the three band gaps viz. zero averaged refractive index (zero-nbar) gap, zero permittivity (zero- ε) and zero permeability (zero- μ) gaps. It is found that for m ≥ 1 , zero- μ gap appears in TE mode and zero- ε gap appears in TM mode. The width of both zero- μ and zero- ε gap increases by increasing m values, but the enhancement of zero- μ gap is more appreciable. Also, the effect of ρ0 on the three band gaps (reflection bands) of annular PC structure at the given m-number has been studied, for both TE and TM polarizations. The result shows that in both polarizations zero- ε and zero- μ gaps decreases when ρ0 increases, whereas zero-nbar gap remains invariant.

Pediatric drug formulation of sodium benzoate extended-release granules.

PubMed

Combescot, E; Morat, G; de Lonlay, P; Boudy, V

2016-01-01

Urea cycle disorders are a group of inherited orphan diseases leading to hyperammonemia. Current therapeutic strategy includes high doses of sodium benzoate leading to three or four oral intakes per day. As this drug is currently available in capsules or in solution, children are either unable to swallow the capsule or reluctant to take the drug due to its strong bitter taste. The objective of the present study was to develop solid, multiparticulate formulations of sodium benzoate, which are suitable for pediatric patients (i.e. flavor-masked, easy to swallow and with a dosing system). Drug layering and coating in a fluidized bed were applied for preparing sustained-release granules. Two types of inert cores (GalenIQ® and Suglets®) and three different polymers (Kollicoat®, Aquacoat® and Eudragit®) were tested in order to select the most appropriate polymer and starter core for our purpose. Physical characteristics and drug release profiles of the pellets were evaluated. A Suglets® core associated with a Kollicoat® coating seems to be the best combination for an extended release of sodium benzoate. A curing period of 8 h was necessary to complete film formation and the resulting drug release pattern was found to be dependent of the acidity of the release medium.

Insights and possible resolution to the information loss paradox via the tunneling picture

NASA Astrophysics Data System (ADS)

Singleton, Douglas; Vagenas, Elias C.; Zhu, Tao; Ren, Ji-Rong

2010-08-01

This paper investigates the information loss paradox in the WKB/tunneling picture of Hawking radiation. In the tunneling picture one can obtain the tunneling amplitude to all orders in ℏ. However all terms beyond the lowest, semi-classical term involve unknown constants. Despite this we find that one can still arrive at interesting restrictions on Hawking radiation to all orders in ℏ: (i) Taking into account only quantum corrections the spectrum remains thermal to all orders. Thus quantum corrections by themselves will not resolve the information loss paradox. (ii) The quantum corrections do imply that the temperature of the radiation goes to zero as the mass of the black hole goes to zero. This is in contrast to the lowest order result where the radiation temperature diverges as the mass of the black hole goes to zero. (iii) Finally we show that by taking both quantum corrections and back reaction into account it is possible under specific conditions to solve the information paradox by having the black hole evaporate completely with the information carried away by the correlations of the outgoing radiation.

Algebraic Riccati equations in zero-sum differential games

NASA Technical Reports Server (NTRS)

Johnson, T. L.; Chao, A.

1974-01-01

The procedure for finding the closed-loop Nash equilibrium solution of two-player zero-sum linear time-invariant differential games with quadratic performance criteria and classical information pattern may be reduced in most cases to the solution of an algebraic Riccati equation. Based on the results obtained by Willems, necessary and sufficient conditions for existence of solutions to these equations are derived, and explicit conditions for a scalar example are given.

Temporal solitons in magnetooptic and metamaterial waveguides

NASA Astrophysics Data System (ADS)

Boardman, A. D.; Hess, O.; Mitchell-Thomas, R. C.; Rapoport, Y. G.; Velasco, L.

2010-09-01

The important topic of temporal soliton propagation in double-negative metamaterials is discussed with an emphasis upon short pulses that exhibit self-steepening controlled by the frequency dependence of the relative permittivity and permeability. In addition, magnetooptic control is included, leading to some fascinating outcomes that should have practical application. The role of self-steepening, Raman scattering, third-order dispersion and magnetooptics is thoroughly investigated, and it is shown that pulses can acquire signatures in the form of additional velocities with respect to the moving frame. The metamaterial influence upon self-steepening has such a strong frequency dependence that it can be used to combat Raman scattering. The self-steepening can change sign, and it is shown that it is possible to arrange pulses in special switching formats to organise the output times. The metamaterial influence upon bit-patterns admits an important degree of control over multi-pulse interactions, and this is combined with magnetooptics to restore patterns. The role of third-order dispersion is also presented. Again, a control of the pulse behaviour in the neighbourhood where the frequency dependence causes the group-velocity dispersion parameter to approach zero is a direct consequence of using this kind of metamaterial. Finally, a Lagrangian analysis is used to support simulations of the positions of the pulse maxima.

Wrinkling of a thin circular sheet bonded to a spherical substrate

PubMed Central

Kohn, Robert V.

2017-01-01

We consider a disc-shaped thin elastic sheet bonded to a compliant sphere. (Our sheet can slip along the sphere; the bonding controls only its normal displacement.) If the bonding is stiff (but not too stiff), the geometry of the sphere makes the sheet wrinkle to avoid azimuthal compression. The total energy of this system is the elastic energy of the sheet plus a (Winkler-type) substrate energy. Treating the thickness of the sheet h as a small parameter, we determine the leading-order behaviour of the energy as h tends to zero, and we give (almost matching) upper and lower bounds for the next-order correction. Our analysis of the leading-order behaviour determines the macroscopic deformation of the sheet; in particular, it determines the extent of the wrinkled region, and predicts the (non-trivial) radial strain of the sheet. The leading-order behaviour also provides insight about the length scale of the wrinkling, showing that it must be approximately independent of the distance r from the centre of the sheet (so that the number of wrinkles must increase with r). Our results on the next-order correction provide insight about how the wrinkling pattern should vary with r. Roughly speaking, they suggest that the length scale of wrinkling should not be exactly constant—rather, it should vary slightly, so that the number of wrinkles at radius r can be approximately piecewise constant in its dependence on r, taking values that are integer multiples of h−a with . This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications’. PMID:28373380

An experiment in vision based autonomous grasping within a reduced gravity environment

NASA Technical Reports Server (NTRS)

Grimm, K. A.; Erickson, J. D.; Anderson, G.; Chien, C. H.; Hewgill, L.; Littlefield, M.; Norsworthy, R.

1992-01-01

The National Aeronautics and Space Administration's Reduced Gravity Program (RGP) offers opportunities for experimentation in gravities of less than one-g. The Extravehicular Activity Helper/Retriever (EVAHR) robot project of the Automation and Robotics Division at the Lyndon B. Johnson Space Center in Houston, Texas, is undertaking a task that will culminate in a series of tests in simulated zero-g using this facility. A subset of the final robot hardware consisting of a three-dimensional laser mapper, a Robotics Research 807 arm, a Jameson JH-5 hand, and the appropriate interconnect hardware/software will be used. This equipment will be flown on the RGP's KC-135 aircraft. This aircraft will fly a series of parabolas creating the effect of zero-g. During the periods of zero-g, a number of objects will be released in front of the fixed base robot hardware in both static and dynamic configurations. The system will then inspect the object, determine the objects pose, plan a grasp strategy, and execute the grasp. This must all be accomplished in the approximately 27 seconds of zero-g.

a Zero-Order Picture of the Infrared Spectrum for the Methoxy Radical: Assignment of States

NASA Astrophysics Data System (ADS)

Johnson, Britta; Sibert, Edwin

2016-06-01

The ground tilde{X}^2E vibrations of the methoxy radical have intrigued both experimentalists and theorists alike due to the presence of a conical intersection at the C3v molecular geometry. This conical intersection causes methoxy's vibrational spectrum to be strongly influenced by Jahn-Teller vibronic coupling which leads to large amplitude vibrations and extensive mixing of the two lowest electronic states. This coupling combined with spin-orbit and Fermi couplings greatly complicates the assignments of states. Using the potential force field and calculated spectra of Nagesh and Sibert1,2, we assign quantum numbers to the infrared spectrum. When the zero-order states are the diabatic normal mode states, there is sufficient mode mixing that the normal mode quantum numbers are poor labels for the final states. We define a series of zero-order Hamiltonians which include additional coupling elements beyond the normal mode picture but still allow for the assignment of Jahn-Teller quantum numbers. In methoxy, the two lowest frequency e} modes, the bend (q_5) and the rock (q_6), are the modes with the strongest Jahn-Teller coupling. In general, a zero-order Hamiltonian which includes first-order Jahn-Teller coupling in q_6 is sufficient for most states of interest. Working in a representation which includes first-order Jahn-Teller coupling in q_6, we identify states in which additional coupling elements must be included; these couplings include first-order Jahn-Teller coupling in q_5, higher order Jahn-Teller coupling in q_5 and q_6, and, in the dueterated case, Jahn-Teller coupling which is modulated by the corresponding a modes. [^1] Nagesh, J.; Sibert, E. L. J. Phys. Chem. A 2012, 116, 3846-3855. Lee, Y.F.; Chou, W.T.; Johnson, B.A.; Tabor, D.P. ; Sibert, E.L.; Lee, Y.P. J. Mol. Spectrosc. 2015, 310, 57-67. Barckholtz, T. A.; Miller, T. A. Int. Revs. in Phys. Chem. 1998, 17, 435-524.

A second-order shock-expansion method applicable to bodies of revolution near zero lift

NASA Technical Reports Server (NTRS)

1957-01-01

A second-order shock-expansion method applicable to bodies of revolution is developed by the use of the predictions of the generalized shock-expansion method in combination with characteristics theory. Equations defining the zero-lift pressure distributions and the normal-force and pitching-moment derivatives are derived. Comparisons with experimental results show that the method is applicable at values of the similarity parameter, the ratio of free-stream Mach number to nose fineness ratio, from about 0.4 to 2.

Freely Drifting Swallow Float Array: August 1988 Trip Report

DTIC Science & Technology

1989-01-01

situ meas- urements of the floats’ clock drifts were obtained; the absolute drifts were on the order of / one part in 105 and the relative clock...Finally, in situ meas- urements of the floats’ clock drifts were obtained, the absolute drifts were on the order of one part in W05 and the relative...FSK mode). That is, the pseudo-random noise generator (PRNG) created a string of ones and zeros ; a zero caused a 12 kHz tone to be broadcast from

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.

Numerical radius and zero pattern of matrices

NASA Astrophysics Data System (ADS)

Nikiforov, Vladimir

2008-01-01

Let A be an n×n complex matrix and r be the maximum size of its principal submatrices with no off-diagonal zero entries. Suppose A has zero main diagonal and x is a unit n-vector. Then, letting ||A|| be the Frobenius norm of A, we show that2[less-than-or-equals, slant](1-1/2r-1/2n)||A||2. This inequality is tight within an additive term O(rn-2). If the matrix A is Hermitian, then2[less-than-or-equals, slant](1-1/r)||A||2. This inequality is sharp; moreover, it implies the Turán theorem for graphs.

Prediction of attendance at fitness center: a comparison between the theory of planned behavior, the social cognitive theory, and the physical activity maintenance theory

PubMed Central

Jekauc, Darko; Völkle, Manuel; Wagner, Matthias O.; Mess, Filip; Reiner, Miriam; Renner, Britta

2015-01-01

In the processes of physical activity (PA) maintenance specific predictors are effective, which differ from other stages of PA development. Recently, Physical Activity Maintenance Theory (PAMT) was specifically developed for prediction of PA maintenance. The aim of the present study was to evaluate the predictability of the future behavior by the PAMT and compare it with the Theory of Planned Behavior (TPB) and Social Cognitive Theory (SCT). Participation rate in a fitness center was observed for 101 college students (53 female) aged between 19 and 32 years (M = 23.6; SD = 2.9) over 20 weeks using a magnetic card. In order to predict the pattern of participation TPB, SCT and PAMT were used. A latent class zero-inflated Poisson growth curve analysis identified two participation patterns: regular attenders and intermittent exercisers. SCT showed the highest predictive power followed by PAMT and TPB. Impeding aspects as life stress and barriers were the strongest predictors suggesting that overcoming barriers might be an important aspect for working out on a regular basis. Self-efficacy, perceived behavioral control, and social support could also significantly differentiate between the participation patterns. PMID:25717313

Silk-Based Biomaterials for Sustained Drug Delivery

PubMed Central

Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

2014-01-01

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193