Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

PubMed

Tavakoli, Naser; Minaiyan, Mohsen; Tabbakhian, Majid; Pendar, Yaqub

2014-01-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

PubMed

Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

2012-01-01

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

Statistical optimisation of diclofenac sustained release pellets coated with polymethacrylic films.

PubMed

Kramar, A; Turk, S; Vrecer, F

2003-04-30

The objective of the present study was to evaluate three formulation parameters for the application of polymethacrylic films from aqueous dispersions in order to obtain multiparticulate sustained release of diclofenac sodium. Film coating of pellet cores was performed in a laboratory fluid bed apparatus. The chosen independent variables, i.e. the concentration of plasticizer (triethyl citrate), methacrylate polymers ratio (Eudragit RS:Eudragit RL) and the quantity of coating dispersion were optimised with a three-factor, three-level Box-Behnken design. The chosen dependent variables were cumulative percentage values of diclofenac dissolved in 3, 4 and 6 h. Based on the experimental design, different diclofenac release profiles were obtained. Response surface plots were used to relate the dependent and the independent variables. The optimisation procedure generated an optimum of 40% release in 3 h. The levels of plasticizer concentration, quantity of coating dispersion and polymer to polymer ratio (Eudragit RS:Eudragit RL) were 25% w/w, 400 g and 3/1, respectively. The optimised formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. We also studied thermal and surface characteristics of the polymethacrylic films to understand the influence of plasticizer concentration on the drug release from the pellets.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers

PubMed Central

Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

2012-01-01

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid–ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids. PMID:25755991

Thiol derivatization of Xanthan gum and its evaluation as a mucoadhesive polymer.

PubMed

Bhatia, Meenakshi; Ahuja, Munish; Mehta, Heena

2015-10-20

Thiol-derivatization of xanthan gum polysaccharide was carried out by esterification with mercaptopropionic acid and thioglycolic acid. Thiol-derivatization was confirmed by Fourier-transformed infra-red spectroscopy. Xanthan-mercaptopropionic acid conjugate and xanthan-thioglycolic acid conjugate were found to possess 432.68mM and 465.02mM of thiol groups as determined by Ellman's method respectively. Comparative evaluation of mucoadhesive property of metronidazole loaded buccal pellets of xanthan and thiolated xanthan gum using chicken buccal pouch membrane revealed higher ex vivo bioadhesion time of thiolated xanthan gum as compared to xanthan gum. Improved mucoadhesive property of thiolated xanthan gum over the xanthan gum can be attributed to the formation of disulfide bond between mucus and thiolated xanthan gum. In vitro release study conducted using phosphate buffer (pH 6.8) revealed a sustained release profile of metronidazole from thiolated xanthan pellets as compared to xanthan pellets. In conclusion, thiolation of xanthan improves its mucoadhesive property and sustained the release of metronidazole over a prolonged period. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: a technical note.

PubMed

Ige, Pradum Pundlikrao; Gattani, Surendra Ganeshlal

2012-03-01

The aim of the current work was to design and develop matrix pellets of hydroxy propyl methyl cellulose K200M and microcrystalline cellulose in an admixture for a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin hydrochloride (500 mg) were prepared by the pelletization technique using an extruder-spheronizer. Pellets were characterized by differential scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), circularity, roundness, percent drug content, percent production yield, in vitro swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging studies. Optimized pellets were sufficiently porous spheroids, free flowing, had smooth surfaces, had yields up to 75.45 ± 0.52% and had drug content up to 96.45 ± 0.19%. The average particle size of formulations MF2 and MF6 were 1.13 ± 0.41 mm and 1.22 ± 0.18 mm, respectively. Formulation MF6 exhibited strong adhesion, about 94.67%, to goat mucosal tissue, and the desired in vitro swelling, with a sustained drug release profile for 12 h and with retention in the upper small intestine of rabbits for 10 h. We conclude that hydroxy propyl methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio could be an effective carrier for multiple unit controlled delivery of metformin hydrochloride.

Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model.

PubMed

Zhang, Xin; Jia, Weitao; Gu, Yifei; Xiao, Wei; Liu, Xin; Wang, Deping; Zhang, Changqing; Huang, Wenhai; Rahaman, Mohamed N; Day, Delbert E; Zhou, Nai

2010-08-01

The treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. In this work, pellets composed of a chitosan-bonded mixture of borate bioactive glass particles (<50microm) and teicoplanin powder (antibiotic), were evaluated in vitro and in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. When immersed in phosphate-buffered saline, the pellets showed sustained release of teicoplanin over 20-30 days, while the bioactive glass converted to hydroxyapatite (HA) within 7 days, eventually forming a porous HA structure. Implantation of the teicoplanin-loaded pellets in a rabbit tibia osteomyelitis model resulted in the detection of teicoplanin in the blood for about 9 days. The implants converted to a bone-like HA graft, and supported the ingrowth of new bone into the tibia defects within 12 weeks of implantation. Microbiological, histological and scanning electron microscopy techniques showed that the implants provided a cure for the bone infection. The results indicate that the teicoplanin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone ingrowth, could provide a method for treating chronic osteomyelitis. Copyright 2010 Elsevier Ltd. All rights reserved.

Use of proteins to minimize the physical aging of EUDRAGIT sustained release films.

PubMed

Kucera, Shawn A; McGinity, James W; Zheng, Weijia; Shah, Navnit H; Malick, A Waseem; Infeld, Martin H

2007-07-01

The objective of this study was to investigate the influence of two proteins, albumin and type B gelatin, on the physical aging of EUDRAGIT RS 30 D and RL 30 D coated theophylline pellets. The physicomechanical properties of sprayed films, thermal properties of cast films, influence of proteins on the zeta potential and particle size of the dispersion, and the release of proteins from cast films under simulated dissolution conditions were investigated. The release rate of theophylline decreased significantly over time from pellets coated with an acrylic dispersion containing 10% albumin when there was no acidification of the acrylic dispersion; however, when pellets were coated with an acidified EUDRAGIT/albumin dispersion, the theophylline release rate was stable for dosage forms stored in the absence of humidity. The drug release rate was faster for pellets coated with acrylic dispersions containing 10% gelatin compared to the albumin-containing formulations. When sprayed films were stored at 40 degrees C/75% RH, the water vapor permeability decreased significantly for both EUDRAGIT films and those containing EUDRAGIT and albumin; however, there was no significant change in this parameter when 10% gelatin was present. Albumin was released from the acrylic films when the pH of the dissolution media was below the isoelectric point of the protein while no quantitative release of gelatin was observed in pH 1.2 or 7.4 media. The effect of gelatin to prevent the decrease in drug release rate was due to stabilization in water vapor permeability of the film. Acidification of the polymeric dispersion resulted in electrostatic repulsive forces between albumin and the acrylic polymer, which stabilized the drug release rate when the dosage forms were stored in aluminum induction sealed containers at both 40 degrees C/75% RH and 25 degrees C/60% RH.

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.

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

PubMed

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

2016-01-01

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

Determination of surface energies of hot-melt extruded sugar-starch pellets.

PubMed

Yeung, Chi-Wah; Rein, Hubert

2018-02-01

Hot-melt extruded sugar-starch pellets are an alternative for commercial sugar spheres, but their coating properties remain to be studied. Both the European Pharmcopoeia 8.6 and the United States Pharmacopoeia 40 specify the composition of sugar-starch pellets without giving requirements for the manufacturing process. Due to various fabrication techniques, the physicochemical properties of pellets may differ. Therefore, the adhesion energies of three coating dispersions (sustained, enteric and immediate release) on different types of pellets were investigated. In this context, the surface energies of various kinds of corn starch (normal, waxy, high-amylose) and sucrose pellets were analyzed using the sessile drop method, whereas the surface tensions of the coating dispersions were examined using the pendant drop method. The adhesion forces were calculated from the results of these studies. Furthermore, sugar spheres were characterized in terms of particle size distribution, porosity and specific surface area. An increase of the pellets' sucrose content leads to a more porous surface structure, which gives them an enhanced wetting behavior with coating dispersions. The adhesion energies of extruded sugar-starch pellets are similar to those of commercial sugar spheres, which comply with pharmacopeial requirements. Both types of pellets are equally suited for coating.

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

PubMed Central

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

2016-01-01

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

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.

Preparation and evaluation of Vinpocetine self-emulsifying pH gradient release pellets.

PubMed

Liu, Mengqi; Zhang, Shiming; Cui, Shuxia; Chen, Fen; Jia, Lianqun; Wang, Shu; Gai, Xiumei; Li, Pingfei; Yang, Feifei; Pan, Weisan; Yang, Xinggang

2017-11-01

The main objective of this study was to develop a pH gradient release pellet with self-emulsifying drug delivery system (SEDDS), which could not only improve the oral bioavailability of Vinpocetine (VIN), a poor soluble drug, but reduce the fluctuation of plasma concentration. First, the liquid VIN SEDDS formulation was prepared. Then the self-emulsifying pH gradient release pellets were prepared by extrusion spheronization technique, and formulation consisted by the liquid SEDDS, absorbent (colloidal silicon dioxide), penetration enhancer (sodium chloride), microcrystalline cellulose, ethyl alcohol, and three coating materials (HPMC, Eudragit L30D55, Eudragit FS30D) were eventually selected. Three kinds of coated pellets were mixed in capsules with the mass ratio of 1:1:1. The release curves of capsules were investigated in vitro under the simulated gastrointestinal conditions. In addition, the oral bioavailability and pharmacokinetics of VIN self-emulsifying pH gradient release pellets, commercial tablets and liquid VIN SEDDS were evaluated in Beagle dogs. The oral bioavailability of self-emulsifying pH gradient release pellets was about 149.8% of commercial VIN tablets, and it was about 86% of liquid VIN SEDDS, but there were no significant difference between liquid SEDDS and self-emulsifying pH gradient release pellets. In conclusion, the self-emulsifying pH gradient release pellets could significantly enhance the absorption of VIN and effectively achieve a pH gradient release. And the self-emulsifying pH gradient release pellet was a promising method to improve bioavailability of insoluble drugs.

Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

PubMed

Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang; Zhang, Changqing

2013-07-01

The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

Gentamicin-Loaded Borate Bioactive Glass Eradicates Osteomyelitis Due to Escherichia coli in a Rabbit Model

PubMed Central

Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang

2013-01-01

The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli. PMID:23629702

Development of a novel osmotically driven drug delivery system for weakly basic drugs.

PubMed

Guthmann, C; Lipp, R; Wagner, T; Kranz, H

2008-06-01

The drug substance SAG/ZK has a short biological half-life and because of its weakly basic nature a strong pH-dependent solubility was observed. The aim of this study was to develop a controlled release (cr) multiple unit pellet formulation for SAG/ZK with pH-independent drug release. Pellets with a drug load of 60% were prepared by extrusion/spheronization followed by cr-film coating with an extended release polyvinyl acetate/polyvinyl pyrrolidone dispersion (Kollidon SR 30 D). To overcome the problem of pH-dependent drug release the pellets were then coated with a second layer of an enteric methacrylic acid and ethyl acrylate copolymer (Kollicoat MAE 30 DP). To increase the drug release rates from the double layered cr-pellets different osmotically active ionic (sodium and potassium chloride) and nonionic (sucrose) additives were incorporated into the pellet core. Drug release studies were performed in media of different osmotic pressure to clarify the main release mechanism. Extended release coated pellets of SAG/ZK demonstrated pH-dependent drug release. Applying a second enteric coat on top of the extended release film coat failed in order to achieve pH-independent drug release. Already low enteric polymer levels on top of the extended release coated pellets decreased drug release rates at pH 1 drastically, thus resulting in a reversal of the pH-dependency (faster release at pH 6.8 than in 0.1N HCl). The addition of osmotically active ingredients (sodium and potassium chloride, and sucrose) increased the imbibing of aqueous fluids into the pellet cores thus providing a saturated drug solution inside the beads and increasing drug concentration gradients. In addition, for these pellets increased formation of pores and cracks in the polymer coating was observed. Hence drug release rates from double layered beads increased significantly. Therefore, pH-independent osmotically driven SAG/ZK release was achieved from pellets containing osmotically active ingredients and coated with an extended and enteric polymer. In contrast, with increasing osmotic pressure of the dissolution medium the in vitro drug release rates decreased significantly.

The influence of Surelease and sodium alginate on the in-vitro release of tamsulosin hydrochloride in pellet dosage form.

PubMed

Kim, Min-Soo; Jun, Seoung Wook; Lee, Sibeum; Lee, Tae Wan; Park, Jeong-Sook; Hwang, Sung-Joo

2005-06-01

The objective of this study was to prepare controlled-release pellets containing 0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers with Surelease and sodium alginate. The release of tamsulosin HCl from pellets coated with the commercial aqueous ethylcellulose dispersion (Surelease) was investigated at different coating loads. In addition, the effect of sodium alginate on drug release was investigated by varying the ratio of sodium alginate to microcrystalline cellulose (MCC). Dissolution studies were first performed in 500 mL simulated gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross sections were examined by scanning electron microscopy (SEM). Apparently, the spherical pellets were prepared using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from Surelease-coated pellets were significantly affected by changing the content of Surelease, the pH of the dissolution medium and the ratio of sodium alginate to MCC. The drug release rates not only decreased with increase in the coating load, but also increased when the pH of the dissolution medium was increased from 1.2 to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results suggest that Surelease and sodium alginate would be useful excipients in the preparation of controlled-release pellets with the desired release profiles.

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.

Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

PubMed

Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

2016-02-29

Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength. Copyright © 2015 Elsevier B.V. All rights reserved.

Sustained subconjunctival protein delivery using a thermosetting gel delivery system.

PubMed

Rieke, Erin R; Amaral, Juan; Becerra, S Patricia; Lutz, Robert J

2010-02-01

An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37 degrees C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.

Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System

PubMed Central

2010-01-01

Purpose: An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. Methods: The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37°C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Results: Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Conclusions: Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye. PMID:20148655

The effect of sodium alginate on physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer.

PubMed

Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

2007-11-01

The aim of this study was to investigate the effect of sodium alginate on the physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The mean values of the shape factor (e(R)) and the aspect ratio of Surelease-matrix pellets were 0.615-0.625 and 1.06-1.070, respectively, indicating good sphericity of the pellets. The drug release rate increased as the amount of sodium alginate increased due to hydration, swelling, and erosion within the Surelease-matrix pellets. In addition, the porosity of pellets also increased with increasing sodium alginate content. The results of this study show that sodium alginate has a greater effect on the drug release rate than the drug release mechanism within the Surelease-matrix for sparingly water-soluble drug, such as tamsulosin hydrochloride.

Minimising alkalinity and pH spikes from Portland cement-bound Bauxsol (seawater-neutralized red mud) pellets for pH circum-neutral waters.

PubMed

Despland, Laure M; Clark, Malcolm W; Aragno, Michel; Vancov, Tony

2010-03-15

Bauxsol reagents (powder, slurry, or pellet forms) are powerful tools in environmental remediation and water and sewage treatment However, when used in circum-neutral water treatments, cement-bound Bauxsol pellets produce a sustained pH and alkalinity spike due to the presence of unreacted CaO in the cement binder. This study developed a pellet treatment system to minimize the alkalinity/pH spike. The recipe for pelletization consisted of Bauxsol powder, ordinary Portland cement (OPC), hydrophilic fumed silica, aluminum powder, a viscosity modifier, and water. Several batches (including different ratios and sizes) were run using modified makeup waters (H(2)0 + CO(2) or NaHCO(3)) or curing brines (CO(2), NaHCO(3), or Mg/CaCl(2)). Alkalinity, pH stability, and slake durability tests were performed on pellets before and/or after curing. The best result for reducing the alkalinity/pH spike was obtained from a MgCl(2), CaCl(2) bath treatment using a Bauxsol:cement ratio of 2.8:1 (pH 8.28; alkalinity 75.1 mg/L) for a 100 g batch or 245:1 (pH 8.05; alkalinity 35.4 mg/L) for a 1 kg batch. Although brine curing does provide a control on pH/alkalinity release, the pellets may still contain unreacted CaO. Therefore, a freshwater rinse of pellets before treating circum-neutral waters is recommended as is the continued investigation of alternative pellet binders.

Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

PubMed Central

Enayatifard, Reza; Mahjoob, Aiding; Ebrahimi, Pouneh; Ebrahimnejad, Pedram

2015-01-01

Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID:26351563

Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using kappa-carrageenan as a pelletizing agent.

PubMed

Kilor, Vaishali A; Sapkal, Nidhi P; Awari, Jasmine G; Shewale, Bharti D

2010-03-01

In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.

[Research of preparation craft of Danshen phenolic acid fast release unit in multi-drug delivery system of Tongmai micro-pellets].

PubMed

Chen, Bin; Xiao, Wei; Jia, Xiao-Bin; Huang, Yang

2012-07-01

To prepare Danshen phenolic acid fast release micro-pellets and study its preparation craft. The factors which could impact yield, extrude shaping, dissolution of Danshen phenolic acid micro-pellets such as wetting agent, drug loading dose, adjuvant, lactose dose, disintegrant, CMS-Na dose and wetting agent dose was investigated. The optimum preparation craft of Danshen phenolic acid fast release micro-pellets was screened out by orhogonal design. Formula of Danshen phenolic acid fast release micro-pellets was calculated as volume dose 50 g. The formula was as follows: principal agent 22.5 g, lactose 5 g, CMS-Na 2 g, MCC 20.5 g, 27 mL 30% ethanol as wetting agent. Extrusion-spheronization was applied. The optimum conditions were screened out as follows: extrusion frequency (25 Hz), spheronization machine frequency (50 Hz), spheronization time (4 min). The process was scientific and rational. The preparation is stable settles basis for multi-drug delivery system of Tongmai micro-pellets.

Use of the direct compression aid Ludiflash(®) for the preparation of pellets via wet extrusion/spheronization.

PubMed

Roblegg, Eva; Schrank, Simone; Griesbacher, Martin; Radl, Stefan; Zimmer, Andreas; Khinast, Johannes

2011-10-01

Conventional solid oral dosage forms are unsuitable for children due to problems associated with swallowing and unpleasant taste. Additionally, the limit of tablets lays in the patient adapted dosing. Therefore, the suitability of Ludiflash(®), a direct compression aid for orally disintegrating tablets, was investigated for the preparation of individually dosable pellets. Micropellets consisting of Ludiflash(®) and small amounts of microcrystalline cellulose were prepared via the wet extrusion/spheronization technique. Paracetamol and ibuprofen were applied as model drugs. The obtained pellets were characterized with respect to drug release and disintegration characteristics, mechanical properties, as well as size and shape. Drug loading was possible up to 30% for ibuprofen and even up to 50% for paracetamol. Higher ibuprofen loadings resulted in considerably slowed drug release and higher paracetamol contents yielded in non-spherical pellets. In vitro release studies revealed that more than 80% of the drug was released within 30 and 60 min for paracetamol and ibuprofen, respectively. Drug release rates were highly influenced by the pellet disintegration behavior. Investigations of the release mechanism using the Korsemeyer-Peppas approach suggested Super Case II drug transport for all paracetamol formulations and anomalous drug transport for most ibuprofen formulations. All pellets exhibited a low porosity and friability, as well as a sufficiently high tensile strength, which was significantly influenced by the type of model drug. Ludiflash(®) can be applied as main excipient for the preparation of individually dosable pellets combining fast drug release and a high mechanical stability.

Properties of pellets manufactured by wet extrusion/spheronization process using kappa-carrageenan: effect of process parameters.

PubMed

Thommes, Markus; Kleinebudde, Peter

2007-11-09

The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

PubMed Central

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai

2015-01-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. PMID:26416858

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

PubMed

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai; Zhang, Chang-Qing; Rahaman, Mohamed N

2015-12-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets.

PubMed

Korasa, Klemen; Hudovornik, Grega; Vrečer, Franc

2016-10-10

Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

PubMed

Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

2017-04-12

Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax pellets followed Zero-order (R 2  = 0.991-0.995). Similarity test was performed using combination of Geleol ® and Compritol ® (i) as a reference. Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol ® , Compritol ® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

PubMed

Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

2015-07-05

Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets.

PubMed

Körber, Martin; Ciper, Mesut; Hoffart, Valerie; Pearnchob, Nantharat; Walther, Mathias; Macrae, Ross J; Bodmeier, Roland

2011-08-01

Weakly basic drugs and their salts exhibit a decrease in aqueous solubility at higher pH, which can result in pH-dependent or even incomplete release of these drugs from extended release formulations. The objective of this study was to evaluate strategies to set-off the very strong pH-dependent solubility (solubility: 80 mg/ml at pH 2 and 0.02 mg/ml at pH 7.5, factor 4000) of a mesylate salt of weakly basic model drug (pK(a) 6.5), in order to obtain pH-independent extended drug release. Three approaches for pH-independent release were investigated: (1) organic acid addition in the core, (2) enteric polymer addition to the extended release coating and (3) an enteric polymer subcoating below the extended release coating. The layering of aspartic acid onto drug cores as well as the coating of drug cores with an ethylcellulose/Eudragit L (enteric polymer) blend were not effective to avoid the formation of the free base at pH 7.5 and thus failed to significantly improve the completeness of the release compared to standard ethylcellulose/hydroxypropyl cellulose (EC/HPC)-coated drug pellets. Interestingly, the incorporation of an enteric polymer layer underneath the EC/HPC coating decreased the free base formation at pH 7.5 and thus resulted in a more complete release of up to 90% of the drug loading over 18 h. The release enhancing effect was attributed to an extended acidification through the enteric polymer layer. Flexible release patterns with approximately pH-independent characteristics were successfully achieved. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

NASA Astrophysics Data System (ADS)

Sasikumar, Swamiappan

2013-09-01

Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

Characterizations of Plasticized Polymeric Film Coatings for Preparing Multiple-Unit Floating Drug Delivery Systems (muFDDSs) with Controlled-Release Characteristics

PubMed Central

Chen, Ying-Chen; Wang, Yu-Chun; Ho, Hsiu-O; Sheu, Ming-Thau

2014-01-01

Effervescent multiple-unit floating drug delivery systems (muFDDSs) consisting of drug (lorsartan)- and effervescent (sodium bicarbonate)-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young’s modulus, and toughness) of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE) and cellulosic materials (ethyl cellulose (EC), and Surelease) were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC) or diethyl phthalate (DEP) resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF) and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems. PMID:24967594

Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

PubMed Central

Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

2011-01-01

In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

Pellet Feed for Dendritic-Web Growth

NASA Technical Reports Server (NTRS)

Duncan, C. S.; Skutch, M. E.; Mchugh, J. P.

1983-01-01

Melt replenishment system sustains continuous growth of silicon dentritic web for several days. Substantially increases size of batch, limited mainly by level of impurities and life of crucible. Silicon pellets automatically added to crucible sustain crystal growth for days.

Non-destructive evaluation of polymer coating structures on pharmaceutical pellets using full-field optical coherence tomography.

PubMed

Li, Chen; Zeitler, J Axel; Dong, Yue; Shen, Yao-Chun

2014-01-01

Full-field optical coherence tomography (FF-OCT) using a conventional light-emitting diode and a complementary metal-oxide semiconductor camera has been developed for characterising coatings on small pellet samples. A set of en-face images covering an area of 700 × 700 μm(2) was taken over a depth range of 166 μm. The three-dimensional structural information, such as the coating thickness and uniformity, was subsequently obtained by analysis of the recorded en-face images. Drug-loaded pharmaceutical sustained-release pellets with two coating layers and of a sub-millimetre diameter were studied to demonstrate the usefulness of the developed system. We have shown that both coatings can be clearly resolved and the thickness was determined to be 40 and 50 μm for the outer and inner coating layers, respectively. It was also found that the outer coating layer is relatively uniform, whereas the inner coating layer has many particle-like features. X-ray computed microtomography measurements carried out on the same pellet sample confirmed all these findings. The presented FF-OCT approach is inexpensive and has better spatial resolution compared with other non-destructive analysis techniques such as terahertz pulsed imaging, and is thus considered advantageous for the quantitative analysis of thin coatings on small pellet samples. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Simulation and parametric study of a film-coated controlled-release pharmaceutical.

PubMed

Borgquist, Per; Zackrisson, Gunnar; Nilsson, Bernt; Axelsson, Anders

2002-04-23

Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.

Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism: in vitro and in vivo evaluation.

PubMed

Lu, Jing; Kan, Shuling; Zhao, Yi; Zhang, Wenli; Liu, Jianping

2016-09-01

The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO(®). In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC0-t (p < 0.01), 1.67 times more than that of EMZ-IRPs, and prolonged mean residence time (7.55 ± 0.12 h) than that of IRPs (1.46 ± 0.39 h). NAP-CSPs and NAP-ECPs showed similar AUC0-t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

PubMed

de Alencar, Rodrigo Gomes; de Oliveira, Aline Carlos; Lima, Eliana Martins; da Cunha-Filho, Marcílio Sérgio Soares; Taveira, Stephânia Fleury; Marreto, Ricardo Neves

2017-08-01

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

Doped Halloysite Nanotubes for Use in the 3D Printing of Medical Devices.

PubMed

Weisman, Jeffery A; Jammalamadaka, Udayabhanu; Tappa, Karthik; Mills, David K

2017-12-15

Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections.

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

PubMed

Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

2010-02-01

Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

Transit of pharmaceutical dosage forms through the small intestine.

PubMed Central

Davis, S S; Hardy, J G; Fara, J W

1986-01-01

The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract. PMID:3732895

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.

Electrochemical fecal pellet sensor for simultaneous real-time ex vivo detection of colonic serotonin signalling and motility

NASA Astrophysics Data System (ADS)

Morris, Rachel; Fagan-Murphy, Aidan; MacEachern, Sarah J.; Covill, Derek; Patel, Bhavik Anil

2016-03-01

Various investigations have focused on understanding the relationship between mucosal serotonin (5-HT) and colonic motility, however contradictory studies have questioned the importance of this intestinal transmitter. Here we described the fabrication and use of a fecal pellet electrochemical sensor that can be used to simultaneously detect the release of luminal 5-HT and colonic motility. Fecal pellet sensor devices were fabricated using carbon nanotube composite electrodes that were housed in 3D printed components in order to generate a device that had shape and size that mimicked a natural fecal pellet. Devices were fabricated where varying regions of the pellet contained the electrode. Devices showed that they were stable and sensitive for ex vivo detection of 5-HT, and no differences in the fecal pellet velocity was observed when compared to natural fecal pellets. The onset of mucosal 5-HT was observed prior to the movement of the fecal pellet. The release of mucosal 5-HT occurred oral to the fecal pellet and was linked to the contraction of the bowel wall that drove pellet propulsion. Taken, together these findings provide new insights into the role of mucosal 5-HT and suggest that the transmitter acts as a key initiator of fecal pellet propulsion.

Effects of polyvinylpyrrolidone both as a binder and pore-former on the release of sparingly water-soluble topiramate from ethylcellulose coated pellets.

PubMed

Yang, Meiyan; Xie, Si; Li, Qiu; Wang, Yuli; Chang, Xinyi; Shan, Li; Sun, Lei; Huang, Xiaoli; Gao, Chunsheng

2014-04-25

Delivering sparingly water-soluble drugs from ethylcellulose (EC) coated pellets with a controlled-release pattern remains challenging. In the present study, hydrophilic polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former in EC coated pellets to deliver sparingly water-soluble topiramate, and the key factors that influenced drug release were identified. When the binder PVP content in drug layers below 20% w/w was decreased, the physical state of topiramate changed from amorphous to crystalline, making much difference to drug solubility and dissolution rates while modifying the drug release profile from first-order to zero-order. In addition, without PVP in drug layering solution, drug layered particles were less sticky during layering process, thus leading to a shorter process and higher loading efficiency. Furthermore, PVP level as a pore-former in EC coating layers mainly governed drug release from the coated pellets with the sensitivity ranging from 23% to 29%. PVP leaching rate and water permeability from EC/PVP film increased with the PVP level, which was perfectly correlated with drug release rate. Additionally, drug release from this formulation was independent of pH of release media or of the paddle mixing speed, but inversely proportional to the osmolality of release media above the physiological range. Copyright © 2014. Published by Elsevier B.V.

Delivering enhanced testosterone replacement therapy through nanochannels.

PubMed

Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

2015-02-18

Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the condition of UO2 nuclear fuel irradiated in a PWR to a burn-up in excess of 110 MWd/kgHM

NASA Astrophysics Data System (ADS)

Restani, R.; Horvath, M.; Goll, W.; Bertsch, J.; Gavillet, D.; Hermann, A.; Martin, M.; Walker, C. T.

2016-12-01

Post-irradiation examination results are presented for UO2 fuel from a PWR fuel rod that had been irradiated to an average burn-up of 105 MWd/kgHM and showed high fission gas release of 42%. The radial distribution of xenon and the partitioning of fission gas between bubbles and the fuel matrix was investigated using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and electron probe microanalysis. It is concluded that release from the fuel at intermediate radial positions was mainly responsible for the high fission gas release. In this region thermal release had occurred from the high burn-up structure (HBS) at some point after the sixth irradiation cycle. The LA-ICP-MS results indicate that gas release had also occurred from the HBS in the vicinity of the pellet periphery. It is shown that the gas pressure in the HBS pores is well below the pressure that the fuel can sustain.

Towards more physiological manipulations of hormones in field studies: comparing the release dynamics of three kinds of testosterone implants, silastic tubing, time-release pellets and beeswax.

PubMed

Quispe, Rene; Trappschuh, Monika; Gahr, Manfred; Goymann, Wolfgang

2015-02-01

Hormone manipulations are of increasing interest in the areas of physiological ecology and evolution, because hormones are mediators of complex phenotypic changes. Often, however, hormone manipulations in field settings follow the approaches that have been used in classical endocrinology, potentially using supra-physiological doses. To answer ecological and evolutionary questions, it may be important to manipulate hormones within their physiological range. We compare the release dynamics of three kinds of implants, silastic tubing, time-release pellets, and beeswax pellets, each containing 3mg of testosterone. These implants were placed into female Japanese quail, and plasma levels of testosterone measured over a period of 30 days. Testosterone in silastic tubing led to supraphysiological levels. Also, testosterone concentrations were highly variable between individuals. Time-release pellets led to levels of testosterone that were slightly supraphysiological during the first days. Over the period of 30 days, however, testosterone concentrations were more consistent. Beeswax implants led to a physiological increase in testosterone and a relatively constant release. The study demonstrated that hormone implants in 10mm silastic tubing led to a supraphysiological peak in female quail. Thus, the use of similar-sized or even larger silastic implants in males or in other smaller vertebrates needs careful assessment. Time-release pellets and beeswax implants provide a more controlled release and degrade within the body. Thus, it is not necessary to recapture the animal to remove the implant. We propose beeswax implants as an appropriate procedure to manipulate testosterone levels within the physiological range. Hence, such implants may be an effective alternative for field studies. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Influence of plasticizer type and level on the properties of Eudragit S100 matrix pellets prepared by hot-melt extrusion.

PubMed

Schilling, Sandra U; Lirola, Hélène L; Shah, Navnit H; Waseem Malick, A; McGinity, James W

2010-01-01

Matrix-type pellets with controlled-release properties may be prepared by hot-melt extrusion applying a single-step, continuous process. However, the manufacture of gastric-resistant pellets is challenging due to the high glass transition temperature of most enteric polymers and an unacceptably high, diffusion-controlled drug release from the matrix during the acidic phase. The objective was to investigate the influence of three plasticizers (triethyl citrate, methylparaben and polyethylene glycol 8000) at two levels (10% or 20%) on the properties of hot-melt extruded Eudragit S100 matrix pellets. Extrusion experiments showed that all plasticizers produced similar reductions in polymer melt viscosity. Differential scanning calorimetry and powder X-ray diffraction demonstrated that the solid state plasticizers were present in the amorphous state. The drug release in acidic medium was influenced by the aqueous solubility of the plasticizer. Less than 10% drug was released after 2 h at pH 1.2 when triethyl citrate or methylparaben was used, independent of the plasticizer level. Drug release at pH 7.4 resulted from polymer dissolution and was not influenced by low levels of plasticizer, but increased significantly at the 20% level. Mechanical testing by diametral compression demonstrated the high tensile strength of the hot-melt extruded pellets that decreased when plasticizers were present.

Interdiction of hypoglycemia in diabetic children by multiparticulate dosage form with controlled glucose release.

PubMed

Franc, Aleš; Sabadková, Dana; Neumann, David; Pavloková, Sylvie; Kopecká, Pavlína; Muselík, Jan

2016-11-01

Patients tend to evade the occurrence of hypoglycemic episodes by excessive carbohydrate intake. Glucose pellets with delayed release in the time of the maximum effect of insulin can not only prevent hypoglycemia but also eliminate the preventive carbohydrate intake. The pellets can be administered in a mixture with semisolid food. The cores containing glucose in combination with osmotically active agents (croscarmellose sodium, carmellose sodium, polyethylene glycol, or carboxymethyl starch) were prepared by extrusion-spheronization and coated with 15% water ethylcellulose dispersion (Surelease® B NF) in Wurster column (Medipo, Havlíčkův Brod, Czech Republic) into four coating levels (12.5, 25, 35, and 50%). Mean particle size is 0.63-0.73 for cores and 0.82-0.98 for coated pellets. Cores and coated pellets have excellent or good flow properties according to Hausner ratio and Carr index. Aspect ratio ranges from 1.78 to 2.17 for cores and from 1.73 to 2.31 for coated pellets. Dissolution was performed using pH-independent method and method with continual change of pH. The suitable pH-independent release was achieved in the samples containing carboxymethyl starch or polyethylene glycol. Glucose release is enabled by a membrane rupture caused by core swelling. It can be, therefore, assumed that the glucose release profile will not be affected by food or transit time.

Reciprocating pellet press

DOEpatents

Jones, Charles W.

1981-04-07

A machine for pressing loose powder into pellets using a series of reciprocating motions has an interchangeable punch and die as its only accurately machines parts. The machine reciprocates horizontally between powder receiving and pressing positions. It reciprocates vertically to press, strip and release a pellet.

Characterization of biodegradable poly-3-hydroxybutyrate films and pellets loaded with the fungicide tebuconazole.

PubMed

Volova, Tatiana; Zhila, Natalia; Vinogradova, Olga; Shumilova, Anna; Prudnikova, Svetlana; Shishatskaya, Ekaterina

2016-03-01

Biodegradable polymer poly(3-hydroxybutyrate) (P3HB) has been used as a matrix to construct slow-release formulations of the fungicide tebuconazole (TEB). P3HB/TEB systems constructed as films and pellets have been studied using differential scanning calorimetry, X-ray structure analysis, and Fourier transform infrared spectroscopy. TEB release from the experimental formulations has been studied in aqueous and soil laboratory systems. In the soil with known composition of microbial community, polymer was degraded, and TEB release after 35 days reached 60 and 36 % from films and pellets, respectively. That was 1.23 and 1.8 times more than the amount released to the water after 60 days in a sterile aqueous system. Incubation of P3HB/TEB films and pellets in the soil stimulated development of P3HB-degrading microorganisms of the genera Pseudomonas, Stenotrophomonas, Variovorax, and Streptomyces. Experiments with phytopathogenic fungi F. moniliforme and F. solani showed that the experimental P3HB/TEB formulations had antifungal activity comparable with that of free TEB.

Characteristics of pellet injuries to the orbit.

PubMed

Kükner, A Sahap; Yilmaz, Turgut; Celebi, Serdal; Karslioğlu, Safak; Alagöz, Gürsoy; Serin, Didem; Acar, M Akif; Ozveren, M Faik

2009-01-01

To investigate the features of orbital injuries by pellets fired from the front. Retrospective, 4 cases of pellet injuries. Five orbits of 4 patients who sustained pellet injuries received from the front were reviewed retrospectively. The course of injury and results were assessed. Radiological examinations were reviewed. The patients were evaluated between December 1996 and June 2004. Five orbits of 4 patients sustained injuries caused by pellets fired from an anterior direction. The globe in the injured orbit was intact in 2 cases. Severe loss of vision was also present in these 2 globes due to optic nerve involvement. Final visual acuity was down to no light perception in 4 eyes and limited to light perception in 1 eye. The prognosis of orbital pellet injuries is, unfortunately, poor. A pellet passing through the floor of the orbit often causes double perforation of the globe and, once in the orbital aperture, it travels towards the apex as a result of the conical shape of the orbit and lodges in the optic canal or its entrance, severely damaging the optic nerve. Surgery or other treatments are usually unsuccessful. Even if the globe is intact, vision is usually severely impaired. Copyright 2009 S. Karger AG, Basel.

The unaccountability case of plastic pellet pollution.

PubMed

Karlsson, Therese M; Arneborg, Lars; Broström, Göran; Almroth, Bethanie Carney; Gipperth, Lena; Hassellöv, Martin

2018-04-01

Plastic preproduction pellets are found in environmental samples all over the world and their presence is often linked to spills during production and transportation. To better understand how these pellets end up in the environment we assessed the release of plastic pellets from a polyethylene production site in a case study area on the Swedish west coast. The case study encompasses; field measurements to evaluate the level of pollution and pathways, models and drifters to investigate the potential spread and a revision of the legal framework and the company permits. This case study show that millions of pellets are released from the production site annually but also that there are national and international legal frameworks that if implemented could help prevent these spills. Bearing in mind the negative effects observed by plastic pollution there is an urgent need to increase the responsibility and accountability of these spills. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Escherichia coli Survival in, and Release from, White-Tailed Deer Feces

PubMed Central

Fry, Jessica; Ives, Rebecca L.; Rose, Joan B.

2014-01-01

White-tailed deer are an important reservoir for pathogens that can contribute a large portion of microbial pollution in fragmented agricultural and forest landscapes. The scarcity of experimental data on survival of microorganisms in and release from deer feces makes prediction of their fate and transport less reliable and development of efficient strategies for environment protection more difficult. The goal of this study was to estimate parameters for modeling Escherichia coli survival in and release from deer (Odocoileus virginianus) feces. Our objectives were as follows: (i) to measure survival of E. coli in deer pellets at different temperatures, (ii) to measure kinetics of E. coli release from deer pellets at different rainfall intensities, and (iii) to estimate parameters of models describing survival and release of microorganisms from deer feces. Laboratory experiments were conducted to study E. coli survival in deer pellets at three temperatures and to estimate parameters of Chick's exponential model with temperature correction based on the Arrhenius equation. Kinetics of E. coli release from deer pellets were measured at two rainfall intensities and used to derive the parameters of Bradford-Schijven model of bacterial release. The results showed that parameters of the survival and release models obtained for E. coli in this study substantially differed from those obtained by using other source materials, e.g., feces of domestic animals and manures. This emphasizes the necessity of comprehensive studies of survival of naturally occurring populations of microorganisms in and release from wildlife animal feces in order to achieve better predictions of microbial fate and transport in fragmented agricultural and forest landscapes. PMID:25480751

Effects of a sustained-release naloxone pellet on luteinizing hormone secretion in female rats.

PubMed

Gabriel, S M; Simpkins, J W

1983-11-01

Studies were undertaken to develop a naloxone implant capable of chronically blocking opioid receptors for several weeks in an effort to evaluate the effect of this prolonged narcotic antagonism on luteinizing hormone (LH) secretion in female rats. Antagonism of opiate receptors was achieved with a tablet formulation which contained 75 mg naloxone free base and a high content of the insoluble binding material, Mg stearate. Subcutaneous placement of this implant prevented morphine-induced analgesia for 2 weeks and antagonized the LH suppressory effects of morphine (15 or 30 mg/kg) administration. Thus, this naloxone delivery system is capable of chronically occupying the opioid receptors which mediate morphine's effects on analgesia and LH secretion. Despite this, the naloxone pellet only moderately enhanced the initial rate of increase in LH secretion following ovariectomy (day 1) and was ineffective in further augmenting LH secretion at 3 and 7 days after implantation. In rats which were ovariectomized and implanted immediately with estradiol-containing Silastic capsules, the naloxone pellet was ineffective in altering LH secretion 1, 3 or 7 days later. Thus, while chronic exposure to naloxone persistently antagonizes the pharmacologic actions of morphine, the naloxone pellet only transiently blocked the tonic inhibitory effect of endogenous opioid peptides. The mechanism by which the LH secretory effects of naloxone are lost following chronic exposure to the antagonist are at present unknown, but may involve the activation of compensatory mechanisms which are inhibitory to LH secretion.

Mucoadhesive Properties of Thiolated Pectin-Based Pellets Prepared by Extrusion-Spheronization Technique.

PubMed

Martins, André Luiz Lopes; de Oliveira, Aline Carlos; do Nascimento, Carolina Machado Ozório Lopes; Silva, Luís Antônio Dantas; Gaeti, Marilisa Pedroso Nogueira; Lima, Eliana Martins; Taveira, Stephânia Fleury; Fernandes, Kátia Flávia; Marreto, Ricardo Neves

2017-05-01

The aim of this study was to develop mucoadhesive pellets on a thiolated pectin base using the extrusion-spheronization technique. Thiolation of pectin was performed by esterification with thioglycolic acid. The molecular weight and thiol group content of the pectins were determined. Pellets containing pectin, microcrystalline cellulose, and ketoprofen were prepared and their mucoadhesive properties were evaluated through a wash-off test using porcine intestinal mucosa. The in vitro ketoprofen release was also evaluated. Thiolated pectin presented a thiol group content of 0.69 mmol/g. Thiolation caused a 13% increase in polymer molecular weight. Pellets containing thiolated pectin were still adhering to the intestinal mucosa after 480 min and showed a more gradual release of ketoprofen. Conversely, pellets prepared with nonthiolated pectin showed rapid disintegration and detached after only 15 min. It can be concluded that thiolated pectin-based pellets can be considered a potential platform for the development of mucoadhesive drug delivery systems for the oral route. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression.

PubMed

Avgerinos, Theodoros; Kantiranis, Nikolaos; Panagopoulou, Athanasia; Malamataris, Stavros; Kachrimanis, Kyriakos; Nikolakakis, Ioannis

2018-02-01

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit ® RSPO the matrix former and citric acid or Lutrol ® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (P e ) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters. Resistance to extrusion and tablet ejection force were reduced by Lutrol ® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P e correlated with T and resistance to deformation of the corresponding pellets (r 2  = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r 2  = 0.990) and for HME the diffusion coefficient (D e ) and retreat rate constant (k b ) decreased linearly with T (r 2  = 0.934 and 0.972). Lutrol ® F127 and citric acid are efficient plasticizers and Lutrol ® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

Escherichia coli survival in, and release from, white-tailed deer feces.

PubMed

Guber, Andrey K; Fry, Jessica; Ives, Rebecca L; Rose, Joan B

2015-02-01

White-tailed deer are an important reservoir for pathogens that can contribute a large portion of microbial pollution in fragmented agricultural and forest landscapes. The scarcity of experimental data on survival of microorganisms in and release from deer feces makes prediction of their fate and transport less reliable and development of efficient strategies for environment protection more difficult. The goal of this study was to estimate parameters for modeling Escherichia coli survival in and release from deer (Odocoileus virginianus) feces. Our objectives were as follows: (i) to measure survival of E. coli in deer pellets at different temperatures, (ii) to measure kinetics of E. coli release from deer pellets at different rainfall intensities, and (iii) to estimate parameters of models describing survival and release of microorganisms from deer feces. Laboratory experiments were conducted to study E. coli survival in deer pellets at three temperatures and to estimate parameters of Chick's exponential model with temperature correction based on the Arrhenius equation. Kinetics of E. coli release from deer pellets were measured at two rainfall intensities and used to derive the parameters of Bradford-Schijven model of bacterial release. The results showed that parameters of the survival and release models obtained for E. coli in this study substantially differed from those obtained by using other source materials, e.g., feces of domestic animals and manures. This emphasizes the necessity of comprehensive studies of survival of naturally occurring populations of microorganisms in and release from wildlife animal feces in order to achieve better predictions of microbial fate and transport in fragmented agricultural and forest landscapes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Irradiation behaviour of the large grained UO{sub 2} fuel pellet in the transient conditions

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

Kosaka, Yuji; Watanabe, Seiichi; Arakawa, Yasushi

2007-07-01

In order to achieve a high duty fuel rod design, it is the key issue to suppress the fission gas release from the view point of the fuel rod inner pressure design. The large grain UO{sub 2} pellet is one of the candidates to meet such a requirement by reducing the fission gas release especially at high power and/or high burnup. We have demonstrated the fuel performance of the large grain pellet in the PWR irradiation conditions, which was fabricated with no additive but with active UO{sub 2} powder through the conventional pelletizing process for the normal grain size pellet.more » According to the mechanism of the fission gas retention, there may be a concern about the larger gas bubble swelling of the large grain pellet at the power transient conditions which may increase the potential of the PCMI failure. In this paper, we focus on the differences of the dimensional change in comparison among the pellets with the different grain sizes at the power transient conditions. The power ramp tests were carried out on the high burnup fuel rods of normal and large grain pellet with no additive, which had been irradiated in the PWR conditions up to around 60 GWd/t at peak position. The detailed PIE results revealed that the volume increment due to the power ramp clearly showed the dependence on the grain size as well as the fission gas release and suggested that the larger grain with no additive may suppress the gas bubble swelling at the power transient conditions. According to the experimental results, it is concluded that the large grain pellet with no additive does not deteriorate the irradiation performance during the power transient conditions from the view point of the gas bubble swelling. (authors)« less

Influence of the inlet air temperature in a fluid bed coating process on drug release from shellac-coated pellets.

PubMed

Farag, Yassin; Leopold, Claudia Sabine

2011-03-01

Since the introduction of aqueous ammoniacal solutions, shellac regained importance for pharmaceutical applications. However, as shellac is a material obtained from natural resources, its quality and thus its physicochemical properties may vary depending on its origin and the type of refining. In this study theophylline pellets were coated with aqueous solutions of three different commercially available shellac types. The inlet air temperature of the coating process was varied, and its influence on drug release from the coated pellet formulations was investigated. Film formation was correlated to the physicochemical and mechanical properties of the investigated shellac types. Pellets coated at lower temperatures showed distinct cracks in the coating film resulting in a loss of the barrier function during dissolution testing. These cracks were nonreversible by additional curing. The physicochemical and mechanical properties of the investigated shellac types varied significantly and could hardly be related to the drug release performance of the investigated formulations. Obviously, with shellac a minimum inlet air temperature must be exceeded to achieve a coherent coating film. This temperature was dependent on the investigated shellac type.

Ethylcellulose film coating of guaifenesin-loaded pellets: A comprehensive evaluation of the manufacturing process to prevent drug migration.

PubMed

Melegari, Cecilia; Bertoni, Serena; Genovesi, Alberto; Hughes, Kevin; Rajabi-Siahboomi, Ali R; Passerini, Nadia; Albertini, Beatrice

2016-03-01

The aim of the research was to investigate the complete process of pellet production in a Wurster fluidized bed coater in order to determine the main factors affecting the migration phenomenon of a soluble API through the ethycellulose film coating (Surelease®) and hence the long-term stability of the controlled release pellets. Guaifenesin (GFN), as BCS class I model drug, was layered on sugar spheres using a binder-polymer solution containing the dissolved GFN. The drug loaded pellets were then coated with Surelease®. The influence of drug loading (4.5-20.0% w/w), curing conditions (40-60°C and dynamic-static equipment), coating level (12-20% theoretical weight gain) and composition of the binder-layering solution (hypromellose versus Na alginate) on process efficiency (RSDW%), GFN content uniformity (RSDC%), GFN solid state (DSC and XRD) and pellet release profiles was evaluated. The effectiveness of the Surelease film was strongly affected by the ability of GFN to cross the coating layer and to recrystallize on the pellet surface. Results indicated that this behaviour was dependent on the polymer used in the binder-layering solution. Using hypromellose as polymer, GFN recrystallized on the coated pellet surface at both drug loadings. The curing step was necessary to stabilize the film effectiveness at the higher drug loading. Increasing the coating level delayed but did not prevent the GFN diffusion. Replacing hypromellose with Na alginate, reduced the migration of GFN through the film to a negligible amount even after six months of storage and the curing step was not necessary to achieve stable controlled release profiles over storage. Copyright © 2015 Elsevier B.V. All rights reserved.

Microtomographic studies of subdivision of modified-release tablets.

PubMed

Wilczyński, Sławomir; Koprowski, Robert; Duda, Piotr; Banyś, Anna; Błońska-Fajfrowska, Barbara

2016-09-25

The uniformity of dosage units within a certain batch is ensured when each unit contains the active pharmaceutical ingredient (API) within a narrow range around the label claim. For tablets containing a score-line authorised for dose reductions, the European Pharmacopoeia (Ph. Eur.) considers that the uniformity of the tablet parts may be based on weight measurements regardless of the tablet type (immediate or modified release). This is because it is up to the regulatory authorities first to assess whether the tablet may contain a score-line for such use. X-ray microtomography was applied to assess the symmetry of 36 modified release tablets, containing 300mg of theophylline. The sum of the volume and surface area of the pellets in the subdivided tablets were compared. Simulations were carried out to identify the optimal amount of pellets in the tablet mass. The maximum difference in the API content between two subdivided halves was 165.18mg vs 133.83mg. If the amount of pellets in the tablet mass would drop below 13% on the basis of the pellet surface area, then the Ph. Eur. requirements would be exceeded. The amount of pellets in the tablet halves resulting in the greatest variability in API content was 38%. The results of this study indicate that the pellets were not distributed uniformly in the tablet mass. Thus, the uniformity of the dose in both halves of a tablet containing pellets cannot be based on the weight measurements i.e. it is necessary to develop further standards for tablet subdivision. Microtomographic methods are a very interesting alternative to expensive and time-consuming pharmacokinetic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-emulsifying excipient platform for improving technological properties of alginate-hydroxypropylcellulose pellets.

PubMed

Mannina, Paolo; Segale, Lorena; Giovannelli, Lorella; Bonda, Andrea Foglio; Pattarino, Franco

2016-02-29

In this work, alginate, alginate-pectin and alginate-hydroxypropylcellulose pellets were produced by ionotropic gelation and characterized. Ibuprofen was selected as model drug; it was suspended in the polymeric solution in crystalline form or dissolved in a self-emulsifying phase and then dispersed into the polymeric solution. The self-emulsifying excipient platform composed of Labrasol (PEG-8 caprylic/capric glycerides) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), able to solubilize the drug was used to improve the technological and biopharmaceutical properties of the alginate pellets. The pellets had diameters between 1317 and 2026 μm and a high drug content (>51%). DSC analysis showed the amorphous state of drug in the pellets containing the self-emulsifying phase. All the systems restricted drug release in conditions simulating the gastric environment and made the drug completely available at a pH value typical for the intestine. Only alginate-HPC systems containing the drug solubilized into the self-emulsifying phase showed the ability to partially control the release of ibuprofen at neutral pH. The self-emulsifying excipient platform is a useful tool to improve technological and biopharmaceutical properties of alginate-HPC pellets. Copyright © 2015 Elsevier B.V. All rights reserved.

Localized Release of Serotonin (5-Hydroxytryptamine) by a Fecal Pellet Regulates Migrating Motor Complexes in Murine Colon

PubMed Central

HEREDIA, DANTE J.; DICKSON, EAMONN J.; BAYGUINOV, PETER O.; HENNIG, GRANT W.; SMITH, TERENCE K.

2009-01-01

Background & Aims The colonic migrating motor complex (CMMC) is a motor pattern that regulates the movement of fecal matter, through a rhythmic sequence of electrical activity and/or contractions, along the large bowel. CMMCs have largely been studied in empty preparations; we investigated whether local reflexes generated by a fecal pellet modify the CMMC to initiate propulsive activity. Methods Recordings of CMMCs were made from the isolated murine large bowel, with or without a fecal pellet. Transducers were placed along the colon to record muscle tension and propulsive force on the pellet and microelectrodes were used to record electrical activity from circular muscle cells anal and oral of a pellet and in colons without the mucosa. Results Spontaneous CMMCs propagated in both an oral or anal direction. When a pellet was inserted, CMMCs increased in frequency and propagated anally, exerting propulsive force on the pellet. The amplitude of slow waves increased during the CMMC. Localized mucosal stimulation/circumferential stretch evoked a CMMC, regardless of stimulus strength. The serotonin (5-hydroxytryptamine-3) antagonist ondansetron reduced the amplitude of the CMMC, the propulsive force on the pellet, and the response to mucosal stroking, but increased the apparent conduction velocity of the CMMC. Removing the mucosa abolished spontaneous CMMCs, which still could be evoked by electrical stimulation. Conclusions The fecal pellet activates local mucosal reflexes, which release serotonin (5-hydroxytryptamine) from enterochromaffin cells, and stretch reflexes that determine the site of origin and propagation of the CMMC, facilitating propulsion. PMID:19138686

Pellet fuelling requirements to allow self-burning on a helical-type fusion reactor

NASA Astrophysics Data System (ADS)

Sakamoto, R.; Miyazawa, J.; Yamada, H.; Masuzaki, S.; Sagara, A.; the FFHR Design Group

2012-08-01

Pellet refuelling conditions to sustain a self-burning plasma have been investigated by extrapolating the confinement property of the LHD plasma, which appears to be governed by a gyro-Bohm-type confinement property. The power balance of the burning plasma is calculated taking into account the profile change with pellet deposition and subsequent density relaxation. A self-burning plasma is achieved within the scope of conventional pellet injection technology. However, a very small burn-up rate of 0.18% is predicted. Higher velocity pellet injection is effective in improving the burn-up rate by deepening particle deposition, whereas deep fuelling leads to undesirable fluctuation of the fusion output.

Use of Cement Kiln Dust, Blast Furnace Slag and Marble Sludge in the Manufacture of Sustainable Artificial Aggregates by Means of Cold Bonding Pelletization.

PubMed

Colangelo, Francesco; Cioffi, Raffaele

2013-07-25

In this work, three different samples of solid industrial wastes cement kiln dust (CKD), granulated blast furnace slag and marble sludge were employed in a cold bonding pelletization process for the sustainable production of artificial aggregates. The activating action of CKD components on the hydraulic behavior of the slag was explored by evaluating the neo-formed phases present in several hydrated pastes. Particularly, the influence of free CaO and sulfates amount in the two CKD samples on slag reactivity was evaluated. Cold bonded artificial aggregates were characterized by determining physical and mechanical properties of two selected size fractions of the granules for each studied mixture. Eighteen types of granules were employed in C28/35 concrete manufacture where coarser natural aggregate were substituted with the artificial ones. Finally, lightweight concretes were obtained, proving the suitability of the cold bonding pelletization process in artificial aggregate sustainable production.

Use of Cement Kiln Dust, Blast Furnace Slag and Marble Sludge in the Manufacture of Sustainable Artificial Aggregates by Means of Cold Bonding Pelletization

PubMed Central

Colangelo, Francesco; Cioffi, Raffaele

2013-01-01

In this work, three different samples of solid industrial wastes cement kiln dust (CKD), granulated blast furnace slag and marble sludge were employed in a cold bonding pelletization process for the sustainable production of artificial aggregates. The activating action of CKD components on the hydraulic behavior of the slag was explored by evaluating the neo-formed phases present in several hydrated pastes. Particularly, the influence of free CaO and sulfates amount in the two CKD samples on slag reactivity was evaluated. Cold bonded artificial aggregates were characterized by determining physical and mechanical properties of two selected size fractions of the granules for each studied mixture. Eighteen types of granules were employed in C28/35 concrete manufacture where coarser natural aggregate were substituted with the artificial ones. Finally, lightweight concretes were obtained, proving the suitability of the cold bonding pelletization process in artificial aggregate sustainable production. PMID:28811427

GLOBAL WOOD PELLET INDUSTRY AND MARKET – CURRENT DEVELOPMENTS AND OUTLOOK

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

Thrän, Daniela; Peetz, David; Schaubach, Kay

The wood pellet use in the heating and electricity sector has recorded a steady growth in the last years. IEA bioenergy task 40 carried out an update of the situation on the national pellet markets in the most relevant pellet producing countries and the global development as well. Various country specific data is collected and compiled for more than 30 countries, containing updated information about regulatory framework, production, consumption, price trends, quality standards and trade aspects. The analysis confirmed the positive development in terms of production and consumption of wood pellets in almost all countries. In 2015 more than 26more » Mt of wood pellets have been produced and consumed worldwide. Technologies and markets become more mature. Increased international pellet trade needs to be supported by adequate frame condition not only for commerce, but also with regard to sustainability issues.« less

Dissolved and fecal pellet carbon and nitrogen release by zooplankton in tropical waters

NASA Astrophysics Data System (ADS)

Small, Lawrence F.; Fowler, Scott W.; Moore, Stanley A.; LaRosa, Jacques

1983-12-01

Carbon (C) and nitrogen (N) release by tropical zooplankton (mostly copepods) and micronekton (euphausiids, pelagic red crabs, and salps) was investigated near VERTEX particle traps at 18°N, 108°W (in 1981) and 15°40'N, 107°30'W (in 1982). The objective was to assess the significance of fecal pellet release relative to respiratory and dissolved excretory release of C and N and relative to primary production in the same waters. For small (< 300 μm) and large (300 to 500 μm) zooplankton, 38 to 49% more ammonium-nitrogen was excreted than C was respired, relative to body concentrations of N and C, respectively. However, for the same zooplankton, 40 to 54% less fecal N was egested than fecal C, again relative to body C and N contents. This apparent compensation yielded a relatively constant body C:N ratio, and, because of the relatively low ratio of respiratory C to excretory N, implied a protein-based metabolism. The same compensatory relationships were found for euphausiids and red crabs, except the percentages of C and N losses were lower than for the zooplankton. No such compensatory relationship was found for the salps, using respiratory—excretory data from the literature and our own observations of fecal pellet production. Either the literature data were not applicable to our salps, or the salps had a more lipid-based metabolism. Reasonably balanced C and N loss budgets were computed for the small and large zooplankton. Daily fecal pellet C egestion represented only 2 to 3% of both large and small zooplankton body C content, and daily fecal pellet N egestion was <2% of zooplankton body N. Likewise, daily fecal pellet production by small and large zooplankton together accounted for <2% of the daily primary C and N production in the top 100 m of water; that is, 'new' primary production would have had to replace losses of <2% per day to balance fecal pellet losses from large and small zooplankton, presuming all fecal pellets sank below 100 m without being eaten or remineralized. However, the estimate of total C flux through 120 m (from particle trap data) was only 4.4% of primary production, so the fecal pellet flux from small and large zooplankton could have accounted for up to 41% of the total flux. From corollary data, it was estimated that the total vertical C flux could result almost entirely from combined fecal pellet production by the existing zooplankton and micronekton concentrations. The vast majority of the primary C production (95.6%) was supported by respired and dissolved excreted compounds plus any atmospheric inputs.

Absorption of p,p'-dichlorodiphenyldichloroethylene and dieldrin in largemouth bass from a 60-D slow-release pellet and detection using a novel enzyme-linked immunosorbent assay method for blood plasma

USGS Publications Warehouse

Muller, Jennifer K.; Sepulveda, Maria S.; Borgert, Christopher J.; Gross, Timothy S.

2005-01-01

This work describes the uptake of two organochlorine pesticides from slow-release pellets by largemouth bass and the utility of a blood plasma enzyme-linked immunosorbent assay (ELISA) method for exposure verification. We measured blood and tissue levels by gas chromatography/mass spectrometry and by a novel ELISA method, and present a critical comparison of the results.

Blood, sweat, tears and success of technology transfer long-term controlled-release of herbicides

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

Van Voris, P.; Cataldo, D.A.; Burton, F.G.

The problems encountered, the technical difficulties that had to be overcome, and the successful transfer of technology related to controlled-release of pesticides is reviewed. Research on control-release of pesticides to date has resulted in products designed to extend bioactivity for periods of several days, months, or at most, several years. However, research supported by the U.S. Department of Energy directed toward solving problems associated with plant-root penetration through caps and liners engineered to minimize leaching or movement of buried nuclear and chemical wastes has resulted in development of a long-term controlled-release herbicide delivery system designed to stop root growth formore » periods of up to 100 years. Through the unique combination of polymers with a herbicidally active dinitroaniline, a cylindrical pellet was developed that continuously releases a herbicide for a period of up to 100 years. Equilibrium concentration of the herbicide in soil adjacent to the pellet and the bioactive lifetime of the device can be adjusted by changing the size of the pellet; the type of polymer; the type, quality, and quantity of carrier; and/or the concentration and type of dinitroaniline was used.« less

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms.

PubMed

Zhu, Yucun; Mehta, Ketan A; McGinity, James W

2006-01-01

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.

Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

PubMed

Jedinger, N; Schrank, S; Mohr, S; Feichtinger, A; Khinast, J; Roblegg, E

2015-05-01

The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's. Copyright © 2015 Elsevier B.V. All rights reserved.

Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

PubMed

Patel, Hetal; Patel, Kishan; Tiwari, Sanjay; Pandey, Sonia; Shah, Shailesh; Gohel, Mukesh

2016-01-01

Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of methods to improve induction of spermiation in wild-caught carp (Cyprinus carpio carpio), a threatened species from the Caspian Sea basin.

PubMed

Vazirzadeh, Arya; Farhadi, Ahmad; Naseri, Mahmood; Jeffs, Andrew

2016-07-01

Wild carp (Cyprinus carpio carpio) forms the basis of an important fishery in the Southern Caspian Sea Basin which is increasingly underpinned by the release of cultured juveniles. A significant bottleneck to hatchery-rearing of juveniles is the spermiation of male broodstock. Therefore, four approaches to improving spermiation were investigated. The effectiveness of two delivery methods for the sustained release of salmon gonadotropin releasing hormone analogue (sGnRHa; i.e., via intramuscular cholesterol pellet vs emulsion injection) on the spermiation success and duration, sperm quality and quantity over 14days in wild-caught carp were compared to single injection of sGnRHa with Pimozide(®) (Linpe method) or carp pituitary extract (CPE). The consequence of the spermiation treatments on resulting embryonic quality was evaluated for subsequent fertilization and hatching success from wild male carp (mean weight±S.D. 1021±112g). All hormonal treatments, except for Linpe method, led to 100% spermiation of treated fish compared to only 25% in the control with no hormone intervention. The duration of spermiation, as well as the various quantitative variables of the sperm and the mean total sperm production were all generally improved with the sustained hormone delivery compared with the acute treatments. The GnRHa-FIA was the most effective method for improving spermiation. Copyright © 2016. Published by Elsevier B.V.

Energy Input and Quality of Pellets Made from Steam-Exploded Douglas Fir (Pseudotsuga menziesii)

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

Sokhansanj, Shahabaddine; Bi, X.T.; Lim, C. Jim

Ground softwood Douglas fir (Pseudotsuga menziesii) was treated with pressurized saturated steam at 200-220 C (1.6-2.4 MPa) for 5-10 min in a sealed container. The contents of the container were released to the atmosphere for a sudden decompression. The steam-exploded wood particles were dried to 10% moisture content and pelletized in a single-piston-cylinder system. The pellets were characterized for their mechanical strength, chemical composition, and moisture sorption. The steamtreated wood required 12-81% more energy to compact into pellets than the untreated wood. Pellets made from steam-treated wood had a breaking strength 1.4-3.3 times the strength of pellets made from untreatedmore » wood. Steam-treated pellets had a reduced equilibrium moisture content of 2-4% and a reduced expansion after pelletization. There was a slight increase in the high heating value from 18.94 to 20.09 MJ/kg for the treated samples. Steam-treated pellets exhibited a higher lengthwise rigidity compared to untreated pellets.« less

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.

Use of implantable pellets to administer low levels of methyl mercury to fish

USGS Publications Warehouse

Arnold, B.S.; Jagoe, C.H.; Gross, T.S.

1999-01-01

Implantable pellets of methyl mercury chloride were tested in Nile Tilapia (Oreochromis niloticus) to appraise the effectiveness of the method for chronic studies of mercury. Two dosing regimes of 15 and 1.5 grams/CH3HgCl pellet (test 1) and 1 and 0.1 grams/pellet (test 2-3) of methyl mercury chloride were used in three tests. Additional pellets containing only matrix were used as controls. The pellets were inserted into the peritoneal cavity along with a microchip for identification. Three methods of incision closure: sutures and two types of surgical glue, were tested. Pellets used in test one released the dose too fast, resulting in premature death of the fish. Results from test 2 and 3 show blood mercury concentrations over time and tissue levels at necropsy consistent with dose suggesting that this is a viable method of dosing fish.

Coatings from blends of Eudragit® RL and L55: a novel approach in pH-controlled drug release.

PubMed

Wulff, R; Leopold, C S

2014-12-10

The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid-ethyl acrylate copolymers. Pellets were coated with blends of Eudragit(®) RL PO (RL) and Eudragit(®) L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

Feeding-associated alterations in striatal neurotransmitter release

NASA Technical Reports Server (NTRS)

Acworth, I. N.; Ressler, K.; Wurtman, R. J.

1989-01-01

Published evidence suggests a role for dopaminergic (DA) brain pathways in feeding-associated behaviors. Using the novel technique of brain microdialysis of striatal extracellular fluid (ECF) as an index of DA release, Church et al. described increases in levels of DA when animals had limited access to pellets, but not with free access. Dopamine release from the nucleus accumbens did increase with free access to pellets post starvation or after food reward. We used permanently implanted microdialysis probes to measure ECF levels of DA, DOPAC, HVA, and large neutral amino acids (LNAA) for up to 72 hours after implantation among rats experiencing different dietary regimens.

Cryogenic pellet production developments for long-pulse plasma operation

NASA Astrophysics Data System (ADS)

Meitner, S. J.; Baylor, L. R.; Combs, S. K.; Fehling, D. T.; McGill, J. M.; Duckworth, R. C.; McGinnis, W. D.; Rasmussen, D. A.

2014-01-01

Long pulse plasma operation on large magnetic fusion devices require multiple forms of cryogenically formed pellets for plasma fueling, on-demand edge localized mode (ELM) triggering, radiative cooling of the divertor, and impurity transport studies. The solid deuterium fueling and ELM triggering pellets can be formed by extrusions created by helium cooled, twin-screw extruder based injection system that freezes deuterium in the screw section. A solenoid actuated cutter mechanism is activated to cut the pellets from the extrusion, inserting them into the barrel, and then fired by the pneumatic valve pulse of high pressure gas. Fuel pellets are injected at a rate up to 10 Hz, and ELM triggering pellets are injected at rates up to 20 Hz. The radiative cooling and impurity transport study pellets are produced by introducing impurity gas into a helium cooled section of a pipe gun where it deposits in-situ. A pneumatic valve is opened and propellant gas is released downstream where it encounters a passive punch which initially accelerates the pellet before the gas flow around the finishes the pellet acceleration. This paper discusses the various cryogenic pellet production techniques based on the twin-screw extruder, pipe gun, and pellet punch designs.

Cryogenic pellet production developments for long-pulse plasma operation

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

Meitner, S. J.; Baylor, L. R.; Combs, S. K.

Long pulse plasma operation on large magnetic fusion devices require multiple forms of cryogenically formed pellets for plasma fueling, on-demand edge localized mode (ELM) triggering, radiative cooling of the divertor, and impurity transport studies. The solid deuterium fueling and ELM triggering pellets can be formed by extrusions created by helium cooled, twin-screw extruder based injection system that freezes deuterium in the screw section. A solenoid actuated cutter mechanism is activated to cut the pellets from the extrusion, inserting them into the barrel, and then fired by the pneumatic valve pulse of high pressure gas. Fuel pellets are injected at amore » rate up to 10 Hz, and ELM triggering pellets are injected at rates up to 20 Hz. The radiative cooling and impurity transport study pellets are produced by introducing impurity gas into a helium cooled section of a pipe gun where it deposits in-situ. A pneumatic valve is opened and propellant gas is released downstream where it encounters a passive punch which initially accelerates the pellet before the gas flow around the finishes the pellet acceleration. This paper discusses the various cryogenic pellet production techniques based on the twin-screw extruder, pipe gun, and pellet punch designs.« less

Design and optimization of disintegrating pellets of MCC by non-aqueous extrusion process using statistical tools.

PubMed

Gurram, Rajesh Kumar; Gandra, Suchithra; Shastri, Nalini R

2016-03-10

The objective of the study was to design and optimize a disintegrating pellet formulation of microcrystalline cellulose by non-aqueous extrusion process for a water sensitive drug using various statistical tools. Aspirin was used as a model drug. Disintegrating matrix pellets of aspirin using propylene glycol as a non-aqueous granulation liquid and croscarmellose as a disintegrant was developed. Plackett-Burman design was initially conducted to screen and identify the significant factors. Final optimization of formula was performed by response surface methodology using a central composite design. The critical attributes of the pellet dosage forms (dependent variables); disintegration time, sphericity and yield were predicted with adequate accuracy based on the regression model. Pareto charts and contour charts were studied to understand the influence of factors and predict the responses. A design space was constructed to meet the desirable targets of the responses in terms of disintegration time <5min, maximum yield, sphericity >0.95 and friability <1.7%. The optimized matrix pellets were enteric coated using Eudragit L 100. The drug release from the enteric coated pellets after 30min in the basic media was ~93% when compared to ~77% from the marketed pellets. The delayed release pellets stored at 25°C/60% RH were stable for a period of 10mo. In conclusion, it can be stated that the developed process for disintegrating pellets using non-aqueous granulating agents can be used as an alternative technique for various water sensitive drugs, circumventing the application of volatile organic solvents in conventional drug layering on inert cores. The scope of this study can be further extended to hydrophobic drugs, which may benefit from the rapid disintegration property and the use of various hydrophilic excipients used in the optimized pellet formulation to enhance dissolution and in turn improve bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

The mouse cornea micropocket angiogenesis assay.

PubMed

Rogers, Michael S; Birsner, Amy E; D'Amato, Robert J

2007-01-01

The mouse corneal micropocket angiogenesis assay uses the avascular cornea as a canvas to study angiogenesis in vivo. Through the use of standardized slow-release pellets, a predictable angiogenic response is generated over the course of 5 d and then quantified. Uniform slow-release pellets are prepared by mixing purified angiogenic growth factors such as basic fibroblast growth factor or vascular endothelial growth factor with sucralfate (a stabilizer) and Hydron (poly-HEMA (poly(2-hydroxyethyl methacrylate)) to allow slow release). This mixture is applied to a mesh that controls unit size and then allowed to harden. A micropocket is surgically created in the mouse cornea and a pellet implanted. Five days later, the area of the cornea overgrown by the angiogenic response is measured using a slit lamp. A skilled investigator can implant and grade 40 eyes in about 2.5 h. The results of the assay are used to assess the ability of potential therapeutic molecules or genetic differences to modulate angiogenesis in vivo.

Tritium release from neutron-irradiated Li 2O sintered pellets: porosity dependence

NASA Astrophysics Data System (ADS)

Tanifuji, Takaaki; Yamaki, Daiju; Takahashi, Tadashi; Iwamoto, Akira

2000-12-01

The tritium release behaviour from sintered Li 2O pellets of various densities (71-98.5% theoretical density, T.D.) has been investigated by heating tests at a constant rate. It is shown that the tritium release rate depends on porosity at densities above 87% T.D., while no dependence was observed at densities below 86% T.D. The tritium release process is thought to consist of three stages described as follows: (1) the liberation of tritium trapped at point defects due to their recovery (peak at around 570 K); (2) the advection through interconnected pores via adsorption and desorption on their inner walls and diffusion in the gas phase of interconnected pores (peak at around 620 K); (3) the dissolution and release of tritium trapped in closed pores (peaks at around 700, 830 and 1000 K).

Development of a Feedstock-to-Product Chain Model for Densified Biomass Pellets

NASA Astrophysics Data System (ADS)

McPherrin, Daniel

The Q’Pellet is a spherical, torrefied biomass pellet currently under development. It aims to improve on the shortcomings of commercially available cylindrical white and torrefied pellets. A spreadsheet-based model was developed to allow for techno-economic analysis and simplified life cycle analysis of Q’Pellets, torrefied pellets and white pellets. A case study was developed to compare the production of white, torrefied and Q’Pellet production based on their internal rates of return and life cycle greenhouse gas emissions. The case study was based on a commercial scale plant built in Williams Lake BC with product delivery in Rotterdam, Netherlands. Q’Pellets had the highest modelled internal rate of return, at 12.7%, with white pellets at 11.1% and torrefied pellets at 8.0%. The simplified life cycle analysis showed that Q’Pellets had the lowest life cycle greenhouse gas emissions of the three products, 6.96 kgCO2eq/GJ, compared to 21.50 kgCO2eq/GJ for white pellets and 10.08 kgCO2eq/GJ for torrefied pellets. At these levels of life cycle greenhouse gas emissions, white pellets are above the maximum life cycle emissions to be considered sustainable under EU regulations. Sensitivity analysis was performed on the model by modifying input variables, and showed that white pellets are more sensitive to uncontrollable market variables, especially pellet sale prices, raw biomass prices and transportation costs. Monte Carlo analysis was also performed, which showed that white pellet production is less predictable and more likely to lead to a negative internal rate of return compared to Q’Pellet production.

Twenty barrel in situ pipe gun type solid hydrogen pellet injector for the Large Helical Device.

PubMed

Sakamoto, Ryuichi; Motojima, Gen; Hayashi, Hiromi; Inoue, Tomoyuki; Ito, Yasuhiko; Ogawa, Hideki; Takami, Shigeyuki; Yokota, Mitsuhiro; Yamada, Hiroshi

2013-08-01

A 20 barrel solid hydrogen pellet injector, which is able to inject 20 cylindrical pellets with a diameter and length of between 3.0 and 3.8 mm at the velocity of 1200 m/s, has been developed for the purpose of direct core fueling in LHD (Large Helical Device). The in situ pipe gun concept with the use of compact cryo-coolers enables stable operation as a fundamental facility in plasma experiments. The combination of the two types of pellet injection timing control modes, i.e., pre-programing mode and real-time control mode, allows the build-up and sustainment of high density plasma around the density limit. The pellet injector has demonstrated stable operation characteristics during the past three years of LHD experiments.

Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery.

PubMed

Avachat, Amelia M; Shinde, Amol S

2016-01-01

Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES™ for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion-spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES™ system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12 h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5 h) as compared to the CODES™ and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES™] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment.

PubMed

Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M; Mustari, Michael J; McLoon, Linda K

2015-06-01

Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment

PubMed Central

Willoughby, Christy L.; Fleuriet, Jérome; Walton, Mark M.; Mustari, Michael J.; McLoon, Linda K.

2015-01-01

Purpose. Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Methods. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Results. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Conclusions. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus. PMID:26030103

Improved Screw-Thread Lock

NASA Technical Reports Server (NTRS)

Macmartin, Malcolm

1995-01-01

Improved screw-thread lock engaged after screw tightened in nut or other mating threaded part. Device does not release contaminating material during tightening of screw. Includes pellet of soft material encased in screw and retained by pin. Hammer blow on pin extrudes pellet into slot, engaging threads in threaded hole or in nut.

Development of Process Analytical Technology (PAT) methods for controlled release pellet coating.

PubMed

Avalle, P; Pollitt, M J; Bradley, K; Cooper, B; Pearce, G; Djemai, A; Fitzpatrick, S

2014-07-01

This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements. Copyright © 2014 Elsevier B.V. All rights reserved.

A long-acting buprenorphine delivery system.

PubMed

Pontani, R B; Misra, A L

1983-03-01

A subcutaneously implantable buprenorphine delivery system utilizing cholesterol-glyceryltristearate matrix for prolonged release of drug is described. Implantable cylindrical pellets of buprenorphine (cholesterol 36 mg, glyceryltristearate 4 mg, buprenorphine hydrochloride 10 mg), diameter 3 mm, length 6 mm blocked the antinociceptive action (hot plate, 55 degrees C) of 10 mg kg-1 SC challenge dose of morphine in rats for 12 weeks or more (longer periods not evaluated). The cumulative percent release of buprenorphine from the test devices 2, 4, 6, 10 and 12 weeks after implantation was 27.4, 35.9, 37.6, 39.9 and 43.1, respectively. The release of buprenorphine from 10 mg pellets approximated first-order kinetics with half-lives of 0.85 and 50.24 weeks, for alpha and beta phases, respectively. The test devices possess the desirable characteristics of simplicity, biocompatibility, nontoxicity, ease of sterilization with ethylene oxide, small size for ease of insertion and removal, minimal encapsulation by surrounding tissue and an extended period of drug release unaffected by body metabolism. No side effects were seen in implanted rats which fed well and gained weight during entire treatment. Neither deterioration of implant nor any gross anatomic changes at implant site were apparent 12 weeks after pellet implantation.

Airborne particles released by crushing CNT composites

NASA Astrophysics Data System (ADS)

Ogura, I.; Okayama, C.; Kotake, M.; Ata, S.; Matsui, Y.; Gotoh, K.

2017-06-01

We investigated airborne particles released as a result of crushing carbon nanotube (CNT) composites using a laboratory scale crusher with rotor blades. For each crushing test, five pellets (approximately 0.1 g) of a polymer (polystyrene, polyamide, or polycarbonate) containing multiwall CNTs (Nanocyl NC7000 or CNano Flotube9000) or no CNTs were placed in the container of the crusher. The airborne particles released by the crushing of the samples were measured. The real-time aerosol measurements showed increases in the concentration of nanometer- and micrometer-sized particles, regardless of the sample type, even when CNT-free polymers were crushed. The masses of the airborne particles collected on filters were below the detection limit, which indicated that the mass ratios of the airborne particles to the crushed pellets were lower than 0.02%. In the electron microscopic analysis, particles with protruding CNTs were observed. However, free-standing CNTs were not found, except for a poorly dispersed CNT-polystyrene composite. This study demonstrated that the crushing test using a laboratory scale crusher is capable of evaluating the potential release of CNTs as a result of crushing CNT composites. The advantage of this method is that only a small amount of sample (several pieces of pellets) is required.

Controlled Release Oral Delivery of Apigenin Containing Pellets with Antioxidant Activity.

PubMed

Pápay, Zsófia Edit; Kállai-Szabó, Nikolett; Balogh, Emese; Ludányi, Krisztina; Klebovich, Imre; Antal, István

2017-01-01

Drug delivery of phytochemicals has gained interest recently due to their remarkable health effects. Apigenin, a plant flavonoid, has antioxidant, anti-inflammatory and anticancer activities but its delivery is challenging. It could be absorbed through the whole intestine, however, it has poor bioavailability due to its low aqueous solubility. In Europe, the daily intake was estimated to be as low as 3 ± 1 mg. Pellets offer several advantages such as improved bioavailability and various resultant drug release profiles can be obtained by simply mixing pellets with different coatings. The objective of our study was to develop a carrier system containing 20 mg apigenin thus enhancing intake and to offer reduction of oxidative stress which can cause inflammation in the intestine. The apigenin powder was dispersed in aqueous solution of binding material and layered onto the inert cores in a fluidized bed apparatus. The layered cores were further coated with enteric polymers and the process parameters were optimized. The prepared pellets met with the requirements and have good physical characteristic. 10% (w/w) Eudragit® L was suitable for enteric coating with a complete release at pH 6.8 within 1 hour. 15% (w/w) Eudragit® FS coating ensured acid resistance ability and colonic delivery. The therapeutic efficiency was confirmed with antioxidant activity measurement by using DPPH* assay. Enteric coated spheres allow targeted delivery into the intestine and colon thus reaching the main absorption site. Pellets were proved to be an optimal delivery system for apigenin thus providing enhanced apigenin intake. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A reliable protocol for the isolation of viable, chondrogenically differentiated human mesenchymal stem cells from high-density pellet cultures.

PubMed

Ullah, Mujib; Hamouda, Houda; Stich, Stefan; Sittinger, Michael; Ringe, Jochen

2012-12-01

Administration of chondrogenically differentiated mesenchymal stem cells (MSC) is discussed as a promising approach for the regenerative treatment of injured or diseased cartilage. The high-density pellet culture is the standard culture for chondrogenic differentiation, but cells in pellets secrete extracellular matrix (ECM) that they become entrapped in. Protocols for cell isolation from pellets often result in cell damage and dedifferentiation towards less differentiated MSC. Therefore, our aim was to develop a reliable protocol for the isolation of viable, chondrogenically differentiated MSC from high-density pellet cultures. Human bone marrow MSC were chondrogenically stimulated with transforming growth factor-β3, and the cartilaginous structure of the pellets was verified by alcian blue staining of cartilage proteoglycans, antibody staining of cartilage collagen type II, and quantitative real-time reverse-transcription polymerase chain reaction of the marker genes COL2A1 and SOX9. Trypsin and collagenases II and P were tested alone or in combination, and for different concentrations and times, to find a protocol for optimized pellet digestion. Whereas trypsin was not able to release viable cells, 90-min digestion with 300 U of collagenase II, 20 U of collagenase P, and 2 mM CaCl2 worked quite well and resulted in about 2.5×10(5) cells/pellet. The protocol was further optimized for the separation of released cells and ECM from each other. Cells were alcian blue and collagen type II positive and expressed COL2A1 and SOX9, verifying a chondrogenic character. However, they had different morphological shapes. The ECM was also uniformly alcian blue and collagen type II positive but showed different organizational and structural forms. To conclude, our protocol allows the reliable isolation of a defined number of viable, chondrogenically differentiated MSC from high-density pellet cultures. Such cells, as well as the ECM components, are of interest as research tools and for cartilage tissue engineering.

Preparation and optimization of glyceryl behenate-based highly porous pellets containing cilostazol.

PubMed

Hwang, Kyu-Mok; Byun, Woojin; Cho, Cheol-Hee; Park, Eun-Seok

2018-06-01

The aim of this study was to prepare a highly porous multiparticulate dosage form containing cilostazol for gastroretentive drug delivery. The floating pellets were prepared with glyceryl behenate as a matrix former and camphor as a sublimating agent by extrusion/spheronization and sublimation under vacuum. Granules prepared with sublimation at 60 °C displayed a slower dissolution rate and smoother surface morphology than those prepared at lower temperatures. This was unexpected as the reported melting point of glyceryl behenate is higher than 69 °C. The DSC study revealed that melting began at a lower temperature owing to the multicomponent property of glyceryl behenate, which led to a sintering effect. The prepared pellets were spherical with unimodal size distribution. They also had porous structures with increased porosity, which led to immediate buoyancy. As cilostazol is a hydrophobic drug that has an erosion-based release mechanism, drug release profile was highly correlated with the percentage of disintegrated pellets. Various excipients were added to the glyceryl behenate-based formulation to increase the floating duration. When hydroxyethyl cellulose was added to the glyceryl behenate-based pellets, acceptable dissolution rate and buoyancy were acquired. This system could potentially be used for gastroretentive delivery of various hydrophobic drugs, which was generally considered difficult.

Preparation and physicochemical characterization of matrix pellets containing APIs with different solubility via extrusion process.

PubMed

Hegyesi, Diána; Thommes, Markus; Kleinebudde, Peter; Sovány, Tamás; Kása, Péter; Kelemen, András; Pintye-Hódi, Klára; Regdon, Géza

2017-03-01

In this study, a multiparticulate matrix system was produced, containing two different active pharmaceutical ingredients (APIs): enalapril-maleate and hydrochlorothiazide. The critical control points of the process were investigated by means of factorial design. Beside the generally used microcrystalline cellulose, ethylcellulose was used as matrix former to achieve modified drug release ensured by diffusion. The matrix pellets were made by extrusion-spheronization using a twin-screw extruder. Some pellet properties (aspect ratio, 10% interval fraction, hardness, deformation process) were determined. The aim of our study was to investigate how the two different APIs with different solubility and particle size influence the process. The amount of the granulation liquid plays a key role in the pellet shaping. A higher liquid feed rate is preferred in the pelletization process.

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

NASA Astrophysics Data System (ADS)

Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylène

2011-10-01

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.

PubMed

Wells, Kevin A; Losin, William G

2008-07-01

Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1 N HCl, < or = 1% of duloxetine was released from the comparator and pellets exposed to applesauce and apple juice. However, the mean dissolution profile of the sample exposed to pudding reported near-total release (90%) after 2 hours in 0.1 N HCl during the gastric challenge portion of the dissolution test. Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. The pellets were stable at room temperature for < or = 2 hours and should quantitatively allow delivery of the full capsule dose, provided that the pellet integrity is maintained (ie, not crushed, chewed, or otherwise broken). Therefore, mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating, suggesting that pudding may be an unacceptable vehicle for administration.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

PubMed

Shah, Neha; Mehta, Tejal; Gohel, Mukesh

2017-08-01

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1 , polyvinylpyrrolidone K-90 (PVP K-90)-X 2 , croscarmellose sodium (CCS)-X 3 , and polacrilin potassium (PP)-X 4 . Dependent variables considered were disintegration time (DT)-Y 1 , sphericity-Y 2 , and percent drug release-Y 3 . The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Analytical Method Development and Validation for the Quantification of Acetone and Isopropyl Alcohol in the Tartaric Acid Base Pellets of Dipyridamole Modified Release Capsules by Using Headspace Gas Chromatographic Technique

PubMed Central

2018-01-01

A simple, sensitive, accurate, robust headspace gas chromatographic method was developed for the quantitative determination of acetone and isopropyl alcohol in tartaric acid-based pellets of dipyridamole modified release capsules. The residual solvents acetone and isopropyl alcohol were used in the manufacturing process of the tartaric acid-based pellets of dipyridamole modified release capsules by considering the solubility of the dipyridamole and excipients in the different manufacturing stages. The method was developed and optimized by using fused silica DB-624 (30 m × 0.32 mm × 1.8 µm) column with the flame ionization detector. The method validation was carried out with regard to the guidelines for validation of analytical procedures Q2 demanded by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). All the validation characteristics were meeting the acceptance criteria. Hence, the developed and validated method can be applied for the intended routine analysis. PMID:29686931

Analytical Method Development and Validation for the Quantification of Acetone and Isopropyl Alcohol in the Tartaric Acid Base Pellets of Dipyridamole Modified Release Capsules by Using Headspace Gas Chromatographic Technique.

PubMed

Valavala, Sriram; Seelam, Nareshvarma; Tondepu, Subbaiah; Jagarlapudi, V Shanmukha Kumar; Sundarmurthy, Vivekanandan

2018-01-01

A simple, sensitive, accurate, robust headspace gas chromatographic method was developed for the quantitative determination of acetone and isopropyl alcohol in tartaric acid-based pellets of dipyridamole modified release capsules. The residual solvents acetone and isopropyl alcohol were used in the manufacturing process of the tartaric acid-based pellets of dipyridamole modified release capsules by considering the solubility of the dipyridamole and excipients in the different manufacturing stages. The method was developed and optimized by using fused silica DB-624 (30 m × 0.32 mm × 1.8  µ m) column with the flame ionization detector. The method validation was carried out with regard to the guidelines for validation of analytical procedures Q2 demanded by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). All the validation characteristics were meeting the acceptance criteria. Hence, the developed and validated method can be applied for the intended routine analysis.

Pharmaceutical approaches to preparing pelletized dosage forms using the extrusion-spheronization process.

PubMed

Trivedi, Namrata R; Rajan, Maria Gerald; Johnson, James R; Shukla, Atul J

2007-01-01

Pelletized dosage forms date back to the 1950s, when the first product was introduced to the market. Since then, these dosage forms have gained considerable popularity because of their distinct advantages, such as ease of capsule filling because of better flow properties of the spherical pellets; enhancement of drug dissolution; ease of coating; sustained, controlled, or site-specific delivery of the drug from coated pellets; uniform packing; even distribution in the GI tract; and less GI irritation. Pelletized dosage forms can be prepared by a number of techniques, including drug layering on nonpareil sugar or microcrystalline cellulose beads, spray drying, spray congealing, rotogranulation, hot-melt extrusion, and spheronization of low melting materials or extrusion-spheronization of a wet mass. This review discusses recent developments in the pharmaceutical approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process over the last decade. The review is divided into three parts: the first part discusses the extrusion-spheronization process, the second part discusses the effect of varying formulation and process parameters on the properties of the pellets, and the last part discusses the different approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process.

In-line monitoring of pellet coating thickness growth by means of visual imaging.

PubMed

Oman Kadunc, Nika; Sibanc, Rok; Dreu, Rok; Likar, Boštjan; Tomaževič, Dejan

2014-08-15

Coating thickness is the most important attribute of coated pharmaceutical pellets as it directly affects release profiles and stability of the drug. Quality control of the coating process of pharmaceutical pellets is thus of utmost importance for assuring the desired end product characteristics. A visual imaging technique is presented and examined as a process analytic technology (PAT) tool for noninvasive continuous in-line and real time monitoring of coating thickness of pharmaceutical pellets during the coating process. Images of pellets were acquired during the coating process through an observation window of a Wurster coating apparatus. Image analysis methods were developed for fast and accurate determination of pellets' coating thickness during a coating process. The accuracy of the results for pellet coating thickness growth obtained in real time was evaluated through comparison with an off-line reference method and a good agreement was found. Information about the inter-pellet coating uniformity was gained from further statistical analysis of the measured pellet size distributions. Accuracy and performance analysis of the proposed method showed that visual imaging is feasible as a PAT tool for in-line and real time monitoring of the coating process of pharmaceutical pellets. Copyright © 2014 Elsevier B.V. All rights reserved.

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.

PubMed

Patadia, Jalashri; Tripathi, Rahul; Joshi, Amita

2016-08-01

Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3(3) FFD. MCC (X1, %), mannitol (X2, %) and Indion 414: Pharmaburst 500 ratio (X3, ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.

Influence of the components of Kollicoat SR film on mechanical properties of floating pellets from the point of view of tableting.

PubMed

Lunio, R; Sawicki, W

2008-10-01

The influence of pellet core ingredients on pellet behaviour, e.g. during compression, is well known. In this study the influence of components of a Kollicoat SR polymer film on mechanical properties was investigated. The aim of this study was to evaluate the influence of polymer film components on the mechanical properties of the pellet as a whole, from the point of view of tableting. Tablets should disintegrate into undeformed pellets floating in this environment for 5-6 h, releasing the model drug--verapamil hydrochloride--if possible in a controlled way. The usefulness of texture analysis and work of compression measurement was also evaluated. Kollicoat SR in the form of a 30D aqueous dispersion was chosen as the main component of the polymer film. Polyvinyl pyrrolidone K-30 as a pore former, and propylene glycol, triethyl citrate and dibutyl sebacate plasticisers were selected as typical additives. The influence of different thickness of polymer film on behaviour during stress was also evaluated. After coating the cores with a 20 microm Kollicoat SR dispersion film, an increase in mechanical strength, in comparison to the pellet core, was observed (2.74 to 3.34 mJ). Addition of porophor increased the work of compression by 50% to 5.1 mJ. The investigation of the influence of plasticiser on film properties proved that the kind of plasticiser used in the polymer film had no effect on the mechanical properties of the film or pellets. Only in the case of the film with triethyl citrate was no distinct of the pellet core found. Pellets coated both with films with triethyl citrate and with dibutyl sebacate, in contrast to pellets with a film coating with propylene glycol, showed a significant decrease of the dissolution rate of verapamil hydrochloride (20, 10 and 40% at 6 hours, respectively). It is possible to compress pellets with a 50 microm polymer film without affecting the dissolution rate, as was confirmed during release studies. When using Kollicoat SR the most appropriate plasticizer seems to be triethyl citrate, and in this case a change of behavior during compression analysis by texture analyzer was observed. But so relationship was found between the type of plasticizer and the work needed to obtain a given deformation.

A novel challenge test incorporating irradiation (60Co) of compost sub-samples to validate thermal lethality towards pathogenic bacteria.

PubMed

Moore, John E; Watabe, Miyuki; Stewart, Andrew; Cherie Millar, B; Rao, Juluri R

2009-01-01

Maturing compost heaps normally attaining temperatures ranging from 55 to 65 degrees C is generally regarded to conform to recommended biological risks and sanitation standards for composts stipulated by either EU or US-EPA. Composted products derived from animal sources are further required by EU biohazard safety regulatory legislation that such composts either attain 70 degrees C for over 3h during maturation or via treatment at 70 degrees C for 1h before being considered for dispensation on land. The setting of the upper limit of thermal lethality at 70 degrees C/1h for achieving biosecurity of the animal waste composted products (e.g. pelleted fertilizer formulations) is not properly substantiated by specific validation tests, comprising a 'wipe-out' step (usually via autoclaving) followed by inoculation of a prescribed bacterium, exposure to 70 degrees C/1h and the lethality determined. Pelleted formulations of composts are not amenable for wet methods (autoclaving) for wipe-out sterilization step as this is detrimental to the pellet and compromises sample integrity. This study describes a laboratory method involving the employment of ((60)Co) irradiation 'wipe-out' step to: (a) compost sub-samples drawn from compost formulation heaps and (b) pelleted products derived from composted animal products while determining the thermal lethality of a given time/temperature (70 degrees C/1h) treatment process and by challenging the irradiated sample (not just with one bacterium but), out with 10 potential food-poisoning organisms from the bacterial genera (Campylobacter, Escherichia, Listeria, Salmonella, Yersinia) frequently detected in pig and poultry farm wastes. This challenge test on compost sub-samples can be a useful intervention ploy for 'inspection and validation' technique for composters during the compost maturity process, whose attainment of temperatures of 55-65 degrees C is presumed sufficient for attainment of sanitation. Stringent measures are further required by law for composted products arising from rural industrialists producing pelleted fertilizers from re-composted animal agriculture wastes comprising pig slurry solids, poultry litter and spent mushroom compost, which carry residual food-borne pathogens with implications to the food chain including humans. Environmentally, sustainable means of recycling farm wastes require that final composted products are free of pathogens in compliance with environmental safety legislation before their release to the market. This test developed provides a science-based risk characterization tool for sustainably managing environmental safety by 'validating' thermal lethality of a given composting process or their derivatives achieved without compromising the sample integrity or ambiguity attached to microbiological validation involving steam sterilization or autoclaving procedures and helps audit the resurgent bacterial populations from surviving non-pathogenic organisms in the end-products of animal waste compost formulations.

Adenosine 5′-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans

PubMed Central

2012-01-01

Background Nutritional supplements designed to increase adenosine 5′-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation. Methods Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000 mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5 h (naso-duodenal tube) or 7 h (pellets) post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests. Results ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by ~50% after administration via proximal-release pellets (P = 0.003) and naso-duodenal tube (P = 0.001), but not after administration via distal-release pellets. Conclusions A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability. PMID:22510240

Preparation and characterization compatible pellets for immobilization of colloidal sulphur nanoparticles

NASA Astrophysics Data System (ADS)

Adlim, M.; Zarlaida, F.; Khaldun, I.; Dewi, R.; Jamilah, M.

2018-03-01

Mercury pollution in atmosphere is dominated by mercury vapour release from coal burning and gold-amalgam separation in gold mining. The initial steps in formulating a compatible mercury absorbent for mercury stabilization was fabrication of pellet supported colloidal sulphur. Sulphur is used to stabilize mercury vapour by formation of metacinnabar that has much lower toxicity. The sulphur reactivity toward mercury vapour can be enhanced by using colloidal sulphur nanoparticles immobilized on compatible pellets. Clay pellets would have heat resistance but in fact, they were less stable in aqueous solution although their stability increased with inclusion of rice husk ash and sawdust or pineapple leaf fibre in the composite. Pellets made of rice husk ash and polyvinyl acetate were stable in water at least for 24 hours. Sulphur from thiosulfate precursor that immobilized onto surface of pellet using chitosan as the stabilizer and the binding agent gave lower sulphur content compared to sulphur from other precursors (sulphur powder and sulphur-CS2). Sulphur from thiosulfate precursor was in form of colloid, has nanosize, and disperse particles on the surface of rice husk ash pellets. Sulphur immobilization methods affect on sulphur particles exposure on the pellet surface.

Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations.

PubMed

Alfarsi, Anas; Dillon, Amy; McSweeney, Seán; Krüse, Jacob; Griffin, Brendan; Devine, Ken; Sherry, Patricia; Henken, Stephan; Fitzpatrick, Stephen; Fitzpatrick, Dara

2018-06-10

There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC. Copyright © 2018 Elsevier B.V. All rights reserved.

Reduction Behavior of Dolomite-Fluxed Magnetite: Coke Composite Pellets at 1573 K (1300 °C)

NASA Astrophysics Data System (ADS)

Park, Hyunsik; Sohn, Il; Tsalapatis, John; Sahajwalla, Veena

2018-06-01

High-temperature behavior of magnetite—coke composite pellet fluxed with dolomite was investigated by customized thermogravimetric analyzer (TGA) at 1573 K (1300 °C). The overall reaction was influenced by C/O ratio and dolomite content. The reduction was accelerated by increased amount of dolomite, while the samples with higher C/O ratio showed the improved reduction degree. X-ray diffraction (XRD) pattern of reduced pellet showed the phase changes of the iron oxides. Noticeable iron peaks were observed when the sample reached the final stage of reduction. CO and CO2 gases released from the reaction were measured by Infrared (IR) gas analyzer. Relation between enhanced reducibility of pellets and larger CO gas evolution from the Boudouard reaction was confirmed from the analysis. Compressive strengths were studied for the practical assessment of reduced pellets. Samples with low-reduction degree showed better physical property. Excessive amount of dolomite also deteriorated the integrity of pellets.

Is Matching Innate?

PubMed Central

Gallistel, C.R; King, Adam Philip; Gottlieb, Daniel; Balci, Fuat; Papachristos, Efstathios B; Szalecki, Matthew; Carbone, Kimberly S

2007-01-01

Experimentally naive mice matched the proportions of their temporal investments (visit durations) in two feeding hoppers to the proportions of the food income (pellets per unit session time) derived from them in three experiments that varied the coupling between the behavioral investment and food income, from no coupling to strict coupling. Matching was observed from the outset; it did not improve with training. When the numbers of pellets received were proportional to time invested, investment was unstable, swinging abruptly from sustained, almost complete investment in one hopper, to sustained, almost complete investment in the other—in the absence of appropriate local fluctuations in returns (pellets obtained per time invested). The abruptness of the swings strongly constrains possible models. We suggest that matching reflects an innate (unconditioned) program that matches the ratio of expected visit durations to the ratio between the current estimates of expected incomes. A model that processes the income stream looking for changes in the income and generates discontinuous income estimates when a change is detected is shown to account for salient features of the data. PMID:17465311

Is matching innate?

PubMed

Gallistel, C R; King, Adam Philip; Gottlieb, Daniel; Balci, Fuat; Papachristos, Efstathios B; Szalecki, Matthew; Carbone, Kimberly S

2007-03-01

Experimentally naive mice matched the proportions of their temporal investments (visit durations) in two feeding hoppers to the proportions of the food income (pellets per unit session time) derived from them in three experiments that varied the coupling between the behavioral investment and food income, from no coupling to strict coupling. Matching was observed from the outset; it did not improve with training. When the numbers of pellets received were proportional to time invested, investment was unstable, swinging abruptly from sustained, almost complete investment in one hopper, to sustained, almost complete investment in the other-in the absence of appropriate local fluctuations in returns (pellets obtained per time invested). The abruptness of the swings strongly constrains possible models. We suggest that matching reflects an innate (unconditioned) program that matches the ratio of expected visit durations to the ratio between the current estimates of expected incomes. A model that processes the income stream looking for changes in the income and generates discontinuous income estimates when a change is detected is shown to account for salient features of the data.

Disruption of the HPA-axis through corticosterone-release pellets induces robust depressive-like behavior and reduced BDNF levels in mice.

PubMed

Demuyser, Thomas; Bentea, Eduard; Deneyer, Lauren; Albertini, Giulia; Massie, Ann; Smolders, Ilse

2016-07-28

The corticosterone mouse model is widely used in preclinical research towards a better understanding of mechanisms of major depression. One particular administration procedure is the subcutaneous implantation of corticosterone slow-release pellets. In this report we want to provide basic evidence, regarding behavioral changes, neurotransmitter and -modulator levels and some other relevant biomolecules after hypothalamic-pituitary-adrenal-axis distortion. We show that three weeks of corticosterone pellet exposure robustly induces depressive-like but not anxiety-like behavior in mice, accompanied by a significant decrease in hippocampal brain-derived neurotrophic factor levels, at five weeks after the start of treatment. Furthermore there is an overall decrease in plasma corticosterone levels after three weeks of treatment that lasts up until the five weeks' time point. On the other hand, no differences are observed in total monoamine, glutamate or d-serine levels, nor in glucocorticoid receptor expression, in various depression-related brain areas. Altogether this characterization delivers vital information, supplementary to existing literature, regarding the phenotyping of pellet-induced hypothalamic-pituitary-adrenal-axis disruption in mice following three weeks of continuous corticosterone exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An oral colon-targeting controlled release system based on resistant starch acetate: synthetization, characterization, and preparation of film-coating pellets.

PubMed

Pu, Huayin; Chen, Ling; Li, Xiaoxi; Xie, Fengwei; Yu, Long; Li, Lin

2011-05-25

An oral colon-targeting controlled release system based on resistant starch acetate (RSA) as a film-coating material was developed. The RSA was successfully synthesized, and its digestion resistibility could be improved by increasing the degree of substitution (DS), which was favorable for the colon-targeting purpose. As a delivery carrier material, the characteristics of RSA were investigated by polarized light microscopy, FTIR spectroscopy, and X-ray diffraction. The results revealed a decrease of the crystallinity of RSA and a change of its crystalline structure from B + V hydrid type to V type. To evaluate the colon-targeting release performance, the RSA film-coated pellets loaded with different bioactive components were prepared by extrusion-spheronization and then by fluid bed coating. The effects of the DS, plasticizer content, and coating thickness of the RSA film and those of the content and molecular weight of the loaded bioactive component on the colon-targeting release performance of the resulting delivery system were investigated. By adjusting the DS, the coating thickness, and the plasticizer content of the RSA film, either the pellets loaded with a small molecular bioactive component such as 5-aminosalicylic acid or those with a macromolecular bioactive peptide or protein such as bovine serum albumin, hepatocyte growth-promoting factor, or insulin showed a desirable colon-targeting release performance. The release percentage was less than 12% in simulated upper gastrointestinal tract and went up to 70% over a period of 40 h in simulated colonic fluid. This suggests that the delivery system based on RSA film has an excellent colon-targeting release performance and the universality for a wide range of bioactive components.

Co-culture of Adult Mesenchymal Stem Cells and Nucleus Pulposus Cells in Bilaminar Pellets for Intervertebral Disc Regeneration.

PubMed

Allon, Aliza A; Schneider, Richard A; Lotz, Jeffrey C

2009-01-01

Our goal is to optimize stem cell-based tissue engineering strategies in the context of the intervertebral disc environment. We explored the benefits of co-culturing nucleus pulposus cells (NPC) and adult mesenchymal stem cells (MSC) using a novel spherical bilaminar pellet culture system where one cell type is enclosed in a sphere of the other cell type. Our 3D system provides a structure that exploits embryonic processes such as tissue induction and condensation. We observed a unique phenomenon: the budding of co-culture pellets and the formation of satellite pellets that separate from the main pellet. MSC and NPC co-culture pellets were formed with three different structural organizations. The first had random organization. The other two had bilaminar organization with either MSC inside and NPC outside or NPC inside and MSC outside. By 14 days, all co-culture pellets exhibited budding and spontaneously generated satellite pellets. The satellite pellets were composed of both cell types and, surprisingly, all had the same bilaminar organization with MSC on the inside and NPC on the outside. This organization was independent of the structure of the main pellet that the satellites stemmed from. The main pellets generated satellite pellets that spontaneously organized into a bilaminar structure. This implies that structural organization occurs naturally in this cell culture system and may be inherently favorable for cell-based tissue engineering strategies. The occurrence of budding and the organization of satellite pellets may have important implications for the use of co-culture pellets in cell-based therapies for disc regeneration. From a therapeutic point of view, the generation of satellite pellets may be a beneficial feature that would serve to spread donor cells throughout the host matrix and restore normal matrix composition in a sustainable way, ultimately renewing tissue function.

Tritium proof-of-principle pellet injector: Phase 2

NASA Astrophysics Data System (ADS)

Fisher, P. W.; Gouge, M. J.

1995-03-01

As part of the International Thermonuclear Engineering Reactor (ITER) plasma fueling development program, Oak Ridge National Laboratory (ORNL) has fabricated a pellet injection system to test the mechanical and thermal properties of extruded tritium. This repeating, single-stage, pneumatic injector, called the Tritium-Proof-of-Principle Phase-2 (TPOP-2) Pellet Injector, has a piston-driven mechanical extruder and is designed to extrude hydrogenic pellets sized for the ITER device. The TPOP-II program has the following development goals: evaluate the feasibility of extruding tritium and DT mixtures for use in future pellet injection systems; determine the mechanical and thermal properties of tritium and DT extrusions; integrate, test and evaluate the extruder in a repeating, single-stage light gas gun sized for the ITER application (pellet diameter approximately 7-8 mm); evaluate options for recycling propellant and extruder exhaust gas; evaluate operability and reliability of ITER prototypical fueling systems in an environment of significant tritium inventory requiring secondary and room containment systems. In initial tests with deuterium feed at ORNL, up to thirteen pellets have been extruded at rates up to 1 Hz and accelerated to speeds of order 1.0-1.1 km/s using hydrogen propellant gas at a supply pressure of 65 bar. The pellets are typically 7.4 mm in diameter and up to 11 mm in length and are the largest cryogenic pellets produced by the fusion program to date. These pellets represent about a 11% density perturbation to ITER. Hydrogenic pellets will be used in ITER to sustain the fusion power in the plasma core and may be crucial in reducing first wall tritium inventories by a process called isotopic fueling where tritium-rich pellets fuel the burning plasma core and deuterium gas fuels the edge.

Important properties of bamboo pellets to be used as commercial solid fuel in China

Treesearch

Zhijia Liu; Benhua Fei; Zehui Jiang; Zhiyong Cai; Xing' e Liu

2014-01-01

Bamboo is a type of biomass material and has great potential as a bioenergy resource of the future in China. Some properties of bamboo pellets, length, diameter, moisture content (MC), particle density, bulk density, durability, fine content, ash, gross calorific value, combustion rate and heat release rate, were determined and the effects of MC and particle size (PS)...

Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata.

PubMed

Sermkaew, Namfa; Ketjinda, Wichan; Boonme, Prapaporn; Phadoongsombut, Narubodee; Wiwattanapatapee, Ruedeekorn

2013-11-20

The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract. Copyright © 2013 Elsevier B.V. All rights reserved.

Physicochemical properties of film-coated melt-extruded pellets.

PubMed

Young, Chistopher R; Crowley, Michael; Dietzsch, Caroline; McGinity, James W

2007-02-01

The purpose of this study was to investigate the physicochemical properties of poly(ethylene oxide) (PEO) and guaifenesin containing beads prepared by a melt-extrusion process and film-coated with a methacrylic acid copolymer. Solubility parameter calculations, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), X-ray powder diffraction (XRPD) and high performance liquid chromatography (HPLC) were used to determine drug/polymer miscibility and/or the thermal processibility of the systems. Powder blends of guaifenesin, PEO and functional excipients were processed using a melt-extrusion and spheronization technique and then film-coated in a fluidized bed apparatus. Solubility parameter calculations were used to predict miscibility between PEO and guaifenesin, and miscibility was confirmed by SEM and observation of a single melting point for extruded drug/polymer blends during MDSC investigations. The drug was stable following melt-extrusion as determined by TGA and HPLC; however, drug release rate from pellets decreased upon storage in sealed HDPE containers with silica desiccants at 40 degrees C/75% RH. The weight loss on drying, porosity and tortuosity determinations were not influenced by storage. Recrystallization of guaifenesin and PEO was confirmed by SEM and XRPD. Additionally, the pellets exhibited a change in adhesion behaviour during dissolution testing. The addition of ethylcellulose to the extruded powder blend decreased and stabilized the drug release rate from the thermally processed pellets. The current study also demonstrated film-coating to be an efficient process for providing melt-extruded beads with pH-dependent drug release properties that were stable upon storage at accelerated conditions.

Orodispersible tablets containing taste-masked solid lipid pellets with metformin hydrochloride: Influence of process parameters on tablet properties.

PubMed

Petrovick, Gustavo Freire; Kleinebudde, Peter; Breitkreutz, Jörg

2018-01-01

Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash ® and Parteck ® ODT) on properties of the tablets (friability, tensile strength, and disintegration time). ODTs (15 mm, flat-faced) with solid lipid pellets (250-1000 µm in diameter) containing 500 mg of metformin HCl, presenting immediate drug release profile and taste-masked properties, were targeted. During compression, a strong lamination of the tablets containing Parteck ® ODT was observed. This phenomenon was prominently observed when high compression forces (≥5 kN) and high excipient amounts (≥40%; w/w) were used. On the other hand, the DoE focused on tablets with Ludiflash ® showed better results regarding the production of ODTs. A positive influence of the compression force on the tensile strength and disintegration time of the tablets, regarding specifications of the Ph. Eur., was observed. The increase in the amount of this excipient resulted in fast disintegrating tablets, however, a negative influence on the tensile strength was noticed. After optimization of the parameters and formulation, based on the DoE results and considering the Ph. Eur. specifications for tablets, ODTs based on lipid pellets containing metformin HCl presenting immediate release profile (85% drug release in less than 30 min) and taste-masked properties (determined by an electronic tongue) were successfully obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

Transatlantic wood pellet trade demonstrates telecoupled benefits

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

Parish, Esther S.; Herzberger, Anna J.; Phifer, Colin C.

European demand for renewable energy resources has led to rapidly increasing transatlantic exports of wood pellets from the southeastern United States (SE US) since 2009. Disagreements have arisen over the global greenhouse gas reductions associated with replacing coal with wood, and groups on both sides of the Atlantic Ocean have raised concerns that increasing biomass exports might negatively affect SE US forests and the ecosystem services they provide. We use the telecoupling framework to test assertions that the intended benefits of the wood pellet trade for Europe might be offset by negative consequences in the SE US. Through a reviewmore » of current literature and available data sets, we characterize the observed and potential changes in the environmental, social, and economic components of the sending and receiving regions to assess the overall sustainability of this renewable energy system. We conclude that the observed transatlantic wood pellet trade is an example of a mutually beneficial telecoupled system with the potential to provide environmental and socioeconomic benefits in both the SE US and Europe despite some negative effects on the coal industry. We recommend continued monitoring of this telecoupled system to quantify the environmental, social, and economic interactions and effects in the sending, receiving, and spillover systems over time so that evidence-based policy decisions can be made with regard to the sustainability of this renewable energy pathway.« less

Transatlantic wood pellet trade demonstrates telecoupled benefits

DOE PAGES

Parish, Esther S.; Herzberger, Anna J.; Phifer, Colin C.; ...

2018-01-01

European demand for renewable energy resources has led to rapidly increasing transatlantic exports of wood pellets from the southeastern United States (SE US) since 2009. Disagreements have arisen over the global greenhouse gas reductions associated with replacing coal with wood, and groups on both sides of the Atlantic Ocean have raised concerns that increasing biomass exports might negatively affect SE US forests and the ecosystem services they provide. We use the telecoupling framework to test assertions that the intended benefits of the wood pellet trade for Europe might be offset by negative consequences in the SE US. Through a reviewmore » of current literature and available data sets, we characterize the observed and potential changes in the environmental, social, and economic components of the sending and receiving regions to assess the overall sustainability of this renewable energy system. We conclude that the observed transatlantic wood pellet trade is an example of a mutually beneficial telecoupled system with the potential to provide environmental and socioeconomic benefits in both the SE US and Europe despite some negative effects on the coal industry. We recommend continued monitoring of this telecoupled system to quantify the environmental, social, and economic interactions and effects in the sending, receiving, and spillover systems over time so that evidence-based policy decisions can be made with regard to the sustainability of this renewable energy pathway.« less

Experimental Study of Thermophysical Properties of Peat Fuel

NASA Astrophysics Data System (ADS)

Mikhailov, A. S.; Piralishvili, Sh. A.; Stepanov, E. G.; Spesivtseva, N. S.

2017-03-01

A study has been made of thermophysical properties of peat pellets of higher-than-average reactivity due to the pretreatment of the raw material. A synchronous differential analysis of the produced pellets was performed to determine the gaseous products of their decomposition by the mass-spectroscopy method. The parameters of the mass loss rate, the heat-release function, the activation energy, the rate constant of the combustion reaction, and the volatile yield were compared to the properties of pellets compressed by the traditional method on a matrix pelletizer. It has been determined that as a result of the peat pretreatment, the yield of volatile components increases and the activation energy of the combustion reaction decreases by 17 and 30% respectively compared with the raw fuel. This determines its prospects for burning in an atomized state at coal-fired thermal electric power plants.

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

PubMed

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

2012-01-01

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

Bacterial Colonization of Pellet Softening Reactors Used during Drinking Water Treatment▿

PubMed Central

Hammes, Frederik; Boon, Nico; Vital, Marius; Ross, Petra; Magic-Knezev, Aleksandra; Dignum, Marco

2011-01-01

Pellet softening reactors are used in centralized and decentralized drinking water treatment plants for the removal of calcium (hardness) through chemically induced precipitation of calcite. This is accomplished in fluidized pellet reactors, where a strong base is added to the influent to increase the pH and facilitate the process of precipitation on an added seeding material. Here we describe for the first time the opportunistic bacterial colonization of the calcite pellets in a full-scale pellet softening reactor and the functional contribution of these colonizing bacteria to the overall drinking water treatment process. ATP analysis, advanced microscopy, and community fingerprinting with denaturing gradient gel electrophoretic (DGGE) analysis were used to characterize the biomass on the pellets, while assimilable organic carbon (AOC), dissolved organic carbon, and flow cytometric analysis were used to characterize the impact of the biological processes on drinking water quality. The data revealed pellet colonization at concentrations in excess of 500 ng of ATP/g of pellet and reactor biomass concentrations as high as 220 mg of ATP/m3 of reactor, comprising a wide variety of different microorganisms. These organisms removed as much as 60% of AOC from the water during treatment, thus contributing toward the biological stabilization of the drinking water. Notably, only a small fraction (about 60,000 cells/ml) of the bacteria in the reactors was released into the effluent under normal conditions, while the majority of the bacteria colonizing the pellets were captured in the calcite structures of the pellets and were removed as a reusable product. PMID:21148700

Bacterial colonization of pellet softening reactors used during drinking water treatment.

PubMed

Hammes, Frederik; Boon, Nico; Vital, Marius; Ross, Petra; Magic-Knezev, Aleksandra; Dignum, Marco

2011-02-01

Pellet softening reactors are used in centralized and decentralized drinking water treatment plants for the removal of calcium (hardness) through chemically induced precipitation of calcite. This is accomplished in fluidized pellet reactors, where a strong base is added to the influent to increase the pH and facilitate the process of precipitation on an added seeding material. Here we describe for the first time the opportunistic bacterial colonization of the calcite pellets in a full-scale pellet softening reactor and the functional contribution of these colonizing bacteria to the overall drinking water treatment process. ATP analysis, advanced microscopy, and community fingerprinting with denaturing gradient gel electrophoretic (DGGE) analysis were used to characterize the biomass on the pellets, while assimilable organic carbon (AOC), dissolved organic carbon, and flow cytometric analysis were used to characterize the impact of the biological processes on drinking water quality. The data revealed pellet colonization at concentrations in excess of 500 ng of ATP/g of pellet and reactor biomass concentrations as high as 220 mg of ATP/m(3) of reactor, comprising a wide variety of different microorganisms. These organisms removed as much as 60% of AOC from the water during treatment, thus contributing toward the biological stabilization of the drinking water. Notably, only a small fraction (about 60,000 cells/ml) of the bacteria in the reactors was released into the effluent under normal conditions, while the majority of the bacteria colonizing the pellets were captured in the calcite structures of the pellets and were removed as a reusable product.

Design of pellet surface grooves for fission gas plenum

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

Carter, T.J.; Jones, L.R.; Macici, N.

1986-01-01

In the Canada deuterium uranium pressurized heavy water reactor, short (50-cm) Zircaloy-4 clad bundles are fueled on-power. Although internal void volume within the fuel rods is adequate for the present once-through natural uranium cycle, the authors have investigated methods for increasing the internal gas storage volume needed in high-power, high-burnup, experimental ceramic fuels. This present work sought to prove the methodology for design of gas storage volume within the fuel pellets - specifically the use of grooves pressed or machined into the relatively cool pellet/cladding interface. Preanalysis and design of pellet groove shape and volume was accomplished using the TRUMPmore » heat transfer code. Postirradiation examination (PIE) was used to check the initial design and heat transfer assumptions. Fission gas release was found to be higher for the grooved pellet rods than for the comparison rods with hollow or unmodified pellets. This had been expected from the initial TRUMP thermal analyses. The ELESIM fuel modeling code was used to check in-reactor performance, but some modifications were necessary to accommodate the loss of heat transfer surface to the grooves. It was concluded that for plenum design purposes, circumferential pellet grooves could be adequately modeled by the codes TRUMP and ELESIM.« less

Continuous corticosterone delivery via the drinking water or pellet implantation: A comparative study in mice.

PubMed

Gasparini, Sylvia J; Weber, Marie-Christin; Henneicke, Holger; Kim, Sarah; Zhou, Hong; Seibel, Markus J

2016-12-01

In order to investigate the effects of glucocorticoid excess in rodent models, reliable methods of continuous glucocorticoid delivery are essential. The current study compares two methods of corticosterone (CS) delivery in regards to their ability to induce typical adverse outcomes such as fat accrual, insulin resistance, sarcopenia and bone loss. Eight-week-old mice received CS for 4weeks either via the drinking water (25-100μgCS/mL) or through weekly surgical implantation of slow release pellets containing 1.5mg CS. Both methods induced abnormal fat mass accrual, inhibited lean mass accretion and bone expansion, suppressed serum osteocalcin levels and induced severe insulin resistance. There was a clear dose dependant relationship between the CS concentrations in the drinking water and the severity of the phenotype, with a concentration of 50μg CS/mL drinking water most closely matching the metabolic changes induced by weekly pellet implantations. In contrast to pellets, however, delivery of CS via the drinking water resulted in a consistent diurnal exposure pattern, closely mimicking the kinetics of clinical glucocorticoid therapy. In addition, the method is safe, inexpensive, easily adjustable, non-invasive and avoids operative stress to the animals. Our data demonstrate that delivery of CS via the drinking water has advantages over weekly implantations of slow-release pellets. A dose of 50μg CS/mL drinking water is appropriate for the investigation of chronic glucocorticoid excess in mice. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Struvite-based fertilizer and its physical and chemical properties.

PubMed

Latifian, Maryam; Liu, Jing; Mattiasson, Bo

2012-12-01

This study describes a method to formulate struvite fine powder into pellets that are easy to spread on agricultural land. To evaluate the quality of produced pellets, some chemical and physical properties commonly measured for fertilizers were tested. The findings indicated that the salt index and heavy metal content ofstruvite pellets were significantly lower than those of commercial NPK fertilizers. In addition, the percentage of nutrient released from struvite pellets after 105 days was in the range of 9.6-23.2, 8.4-26.7 and 11.3-32.6% for nitrogen, phosphorous and magnesium, respectively, which is considerably lower than that of commercial NPK fertilizer. Among different formulations between struvite crystals and binders, starch and bentonite were the most efficient in agglomerating struvite powder, leading to an increase in the crush strength to over the recommended limit of >2.5 kgf for fertilizer hardness.

Gas Control and Thermal Modeling Methods for Pressed Pellet and Fast Rise Thin-Film Thermal Batteries

DTIC Science & Technology

2015-09-01

Thin-Film Thermal Batteries by Frank C Krieger and Michael S Ding Approved for public release; distribution unlimited...Laboratory Gas Control and Thermal Modeling Methods for Pressed Pellet and Fast Rise Thin-Film Thermal Batteries by Frank C Krieger and Michael S...Batteries 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Frank C Krieger and Michael S Ding 5d. PROJECT NUMBER

Shock Reactivity of Non-Porous Mixtures of Manganese and Sulfur

NASA Astrophysics Data System (ADS)

Jetté, F. X.; Goroshin, S.; Higgins, A. J.

2007-12-01

Equimolar mixtures of manganese powder and sulfur were melt-cast into solid pellets in order to study the mechanism of shock-enhanced reactivity in non-porous heterogeneous mixtures. This mixture was selected due to the large exothermic heat release of the manganese-sulfur reaction (214 kJ/mol), which causes the reaction to be self-sustaining once initiated. The test samples were placed in planar recovery ampoules and a strong shock was delivered via the detonation of a charge of amine-sensitized nitromethane. Various shock strengths were achieved by placing different thicknesses of PMMA attenuator discs between the explosive charge and the ampoule. The results confirmed that shock-induced reactions can be produced in highly non-porous mixtures. Indeed, the critical shock pressure that caused ignition of the mixture in the ampoule was found to be in the range 2.2-3.0 GPa (pressures were estimated using LS-DYNA simulations of samples with 100% TMD).

Wood pellets, what else? Greenhouse gas parity times of European electricity from wood pellets produced in the south-eastern United States using different softwood feedstocks

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

Hanssen, Steef V.; Duden, Anna S.; Junginger, Martin

Several EU countries import wood pellets from the south-eastern United States. The imported wood pellets are (co-)fired in power plants with the aim of reducing overall greenhouse gas (GHG) emissions from electricity and meeting EU renewable energy targets. To assess whether GHG emissions are reduced and on what timescale, we construct the GHG balance of wood-pellet electricity. This GHG balance consists of supply chain and combustion GHG emissions, carbon sequestration during biomass growth, and avoided GHG emissions through replacing fossil electricity. We investigate wood pellets from four softwood feedstock types: small roundwood, commercial thinnings, harvest residues, and mill residues. Permore » feedstock, the GHG balance of wood-pellet electricity is compared against those of alternative scenarios. Alternative scenarios are combinations of alternative fates of the feedstock material, such as in-forest decomposition, or the production of paper or wood panels like oriented strand board (OSB). Alternative scenario composition depends on feedstock type and local demand for this feedstock. Results indicate that the GHG balance of wood-pellet electricity equals that of alternative scenarios within 0 to 21 years (the GHG parity time), after which wood-pellet electricity has sustained climate benefits. Parity times increase by a maximum of twelve years when varying key variables (emissions associated with paper and panels, soil carbon increase via feedstock decomposition, wood-pellet electricity supply chain emissions) within maximum plausible ranges. Using commercial thinnings, harvest residues or mill residues as feedstock leads to the shortest GHG parity times (0-6 years) and fastest GHG benefits from wood-pellet electricity. Here, we find shorter GHG parity times than previous studies, for we use a novel approach that differentiates feedstocks and considers alternative scenarios based on (combinations of) alternative feedstock fates, rather than on alternative land-uses. This novel approach is relevant for bioenergy derived from low-value feedstocks.« less

Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity

PubMed Central

Liu, Xiu

2014-01-01

Rationale Overeating beyond individuals’ homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. Objective The present study examined whether a pharmacological stressor, yohimbine enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor receptor (CRF1) blockade by a CFR1 selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Methods Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive-ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. Results The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Conclusions Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity. PMID:25510859

Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity.

PubMed

Liu, Xiu

2015-06-01

Overeating beyond individuals' homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. The present study examined whether a pharmacological stressor, yohimbine, enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor (CRF) receptor blockade by a CRF1-selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity.

Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.

PubMed

Salvioni, Lucia; Fiandra, Luisa; Del Curto, Maria Dorly; Mazzucchelli, Serena; Allevi, Raffaele; Truffi, Marta; Sorrentino, Luca; Santini, Benedetta; Cerea, Matteo; Palugan, Luca; Corsi, Fabio; Colombo, Miriam

2016-08-01

In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibiotic-loaded plaster of Paris implants coated with poly lactide-co-glycolide as a controlled release delivery system for the treatment of bone infections.

PubMed

Benoit, M A; Mousset, B; Delloye, C; Bouillet, R; Gillard, J

1997-01-01

Plaster of Paris implants containing vancomycin (60 mg/g of carrier) were prepared in order to be used as local delivery system for the treatment of bone infections. The regulation of the release rate was performed by coating the carrier with a polylactide-co-glycolide polymer composed by 10% (w/w) polyglycolic acid and 90% (w/w) racemic poly (D,L-lactic acid). The release of the antibiotic from the biodegradable matrix was evaluated in vitro. From this investigation, it is clear that the drug elution depends on the coating depth. After a burst effect occurring on the first day of the experiment, therapeutic concentrations were measured during one week when uncoated implants were used. The coating allowed decrease of the burst effect and extended efficient release to more than five weeks when the implants were embedded with six layers (162 microns) of PLA45GA10. This delivery system was implanted into the femoral condyle of rabbits. It was shown that the in vivo release was also closely regulated by the coating depth. In all bone tissues (bone marrow and cortical bone) surrounding the pellets, the drug concentration exceeded the Minimum Inhibitory Concentration for the common causative organisms of bone infections (Staphylococcus aureus) for at least four weeks without inducing serum toxic levels. Due to its cheapness, facility of use and sterilization, biocompatibility and biodegradability, plaster of Paris coated with PLA45GA10 polymer giving a controlled release of vancomycin appears to be a promising sustained release delivery system of antibiotics for the treatment of bone and joint infections.

Slow-Release Fertilizers For Plants

NASA Technical Reports Server (NTRS)

Ming, Douglas W.; Golden, D. C.

1995-01-01

Synthetic mineral provides growing plants with nutrients, including micronutrients. Dissolves slowly in moist soil or in hydroponic solution, releasing constituents. Mineral synthetic apatite into which nutrients calcium, phosphorous, iron, manganese, copper, zinc, molybdenum, chlorine, boron, and sulfur incorporated in form of various salts. Each pellet has homogeneous inorganic composition. Composition readily adjusted to meet precise needs of plant.

Pellet injection technology

NASA Astrophysics Data System (ADS)

Combs, S. K.

1993-07-01

During the last 10 to 15 years, significant progress has been made worldwide in the area of pellet injection technology. This specialized field of research originated as a possible solution to the problem of depositing atoms of fuel deep within magnetically confined, hot plasmas for refueling of fusion power reactors. Using pellet injection systems, frozen macroscopic (millimeter-size) pellets composed of the isotopes of hydrogen are formed, accelerated, and transported to the plasma for fueling. The process and benefits of plasma fueling by this approach have been demonstrated conclusively on a number of toroidal magnetic confinement configurations; consequently, pellet injection is the leading technology for deep fueling of magnetically confined plasmas for controlled thermonuclear fusion research. Hydrogen pellet injection devices operate at very low temperatures (≂10 K) at which solid hydrogen ice can be formed and sustained. Most injectors use conventional pneumatic (light gas gun) or centrifuge (mechanical) acceleration concepts to inject hydrogen or deuterium pellets at speeds of ≂1-2 km/s. Pellet injectors that can operate at quasi-steady state (pellet delivery rates of 1-40 Hz) have been developed for long-pulse fueling. The design and operation of injectors with the heaviest hydrogen isotope, tritium, offer some special problems because of tritium's radioactivity. To address these problems, a proof-of-principle experiment was carried out in which tritium pellets were formed and accelerated to speeds of 1.4 km/s. Tritium pellet injection is scheduled on major fusion research devices within the next few years. Several advanced accelerator concepts are under development to increase the pellet velocity. One of these is the two-stage light gas gun, for which speeds of slightly over 4 km/s have already been reported in laboratory experiments with deuterium ice. A few two-stage pneumatic systems (single-shot) have recently been installed on tokamak experiments. This article reviews the equipment and instruments that have been developed for pellet injection with emphasis on recent advances. Prospects for future development are addressed, as are possible applications of this technology to other areas of research.

Centrifugal air-assisted melt agglomeration for fast-release "granulet" design.

PubMed

Wong, Tin Wui; Musa, Nafisah

2012-07-01

Conventional melt pelletization and granulation processes produce round and dense, and irregularly shaped but porous agglomerates respectively. This study aimed to design centrifugal air-assisted melt agglomeration technology for manufacture of spherical and yet porous "granulets" for ease of downstream manufacturing and enhancing drug release. A bladeless agglomerator, which utilized shear-free air stream to mass the powder mixture of lactose filler, polyethylene glycol binder and poorly water-soluble tolbutamide drug into "granulets", was developed. The inclination angle and number of vane, air-impermeable surface area of air guide, processing temperature, binder content and molecular weight were investigated with reference to "granulet" size, shape, texture and drug release properties. Unlike fluid-bed melt agglomeration with vertical processing air flow, the air stream in the present technology moved centrifugally to roll the processing mass into spherical but porous "granulets" with a drug release propensity higher than physical powder mixture, unprocessed drug and dense pellets prepared using high shear mixer. The fast-release attribute of "granulets" was ascribed to porous matrix formed with a high level of polyethylene glycol as solubilizer. The agglomeration and drug release outcomes of centrifugal air-assisted technology are unmet by the existing high shear and fluid-bed melt agglomeration techniques. Copyright © 2012 Elsevier B.V. All rights reserved.

Monte Carlo simulation of energy absorbed in phenolic ESR dosimeters added with gadolinium exposed to thermal, epithermal and fast neutrons

NASA Astrophysics Data System (ADS)

Longo, A.; Collura, G.; Gallo, S.; Bartolotta, A.; Marrale, M.

2017-11-01

In this work analyses of the energy released per unit mass in phenolic compound exposed to neutron beams were performed with the aim of predicting the increase in dose achievable by addition of gadolinium (Gd) inside the pellets. In particular, Monte Carlo (MC) simulations were carried out for IRGANOX® 1076 phenolic compound irradiated with neutron beams with different energy spectra at various depths inside a water phantom. The addition of gadolinium increases sensitivity of phenolic ESR (electron spin resonance) dosimeters to neutrons thanks to the high gadolinium cross section for neutron capture and to the large number of secondary particles (mainly Auger and internal conversion electrons) which are able to release energy inside the sensitive material layers. For small depths in water phantom and low energy neutron spectra the increase in dose due to gadolinium is large (more than a factor 50). The enhancement is smaller in case of epithermal neutron beam, whereas the increase in dose for fast neutrons is less than 50%. In order to have a comparison with other ESR dosimeters the energy released per unit mass in phenolic compound was compared with that calculated in alanine pellets. For thermal neutron beams the energy released in phenolic compound with gadolinium is comparable to that released in alanine for small depths in phantom, whereas it is larger than in alanine for large depths. In case of epithermal and fast neutron beams the energy released in phenolic compound is larger than in alanine samples because the elastic scattering with hydrogen nuclei is more probable for high neutron energies and this phenolic compound is characterized by an higher number of 1H nuclei than alanine. All results here found suggest that these phenolic pellets could be fruitfully used for dosimetric applications in Neutron Capture Therapy.

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

PubMed

Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

2012-12-01

The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

PubMed

Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

2010-06-01

Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study discharge and were monitored for adverse events (AEs) throughout the study. Of the 24 subjects enrolled in the study, 23 completed it. Most subjects were white (79%) and male (63%); the mean (SD) age was 39.3 (11.2) years and the mean weight was 77.6 (13.5) kg (range, 55.0102.5 kg). Plasma C(max) and AUC(0-t) of naltrexone after the administration of crushed pellets of MS-sNT (579 pg/mL and 1811 h . pg/mL, respectively) and naltrexone solution (584 pg/mL and 1954 h . pg/mL) were not significantly different; 90% CIs were 83.8% to 116% and 83.3% to 102%, meeting the regulatory requirements for assuming bioequivalence in this study population. Plasma naltrexone concentration was below the lower limit of quantitation (4.0 pg/mL) in 23 of 24 subjects (96%) after whole MS-sNT administration. Morphine AUC(0-t) was not significantly different whether MS-sNT was crushed (163 h . ng/mL) or administered whole (174 h . ng/mL), but C(max) was numerically higher (24.5 vs 7.7 ng/mL) and T(max) was numerically shorter (2.00 vs 7.03 hours) with MS-sNT crushed versus whole. The most commonly reported AEs were nausea (8/23 [35%], 10/24 [42%], and 3/23 [13%] subjects in the crushed, whole, and naltrexone groups, respectively) and emesis (6 [26%], 7 [29%], and 2 [9%]). In this single-dose study, when pellets from MS-sNT were crushed, naltrexone appeared to be completely released and available to mitigate morphine-induced effects. When MS-sNT was administered whole, morphine was released in an extended-release fashion while naltrexone remained sequestered.

Effects of Beryllium and Compaction Pressure on the Thermal Diffusivity of Uranium Dioxide Fuel Pellets

NASA Astrophysics Data System (ADS)

Camarano, D. M.; Mansur, F. A.; Santos, A. M. M.; Ferraz, W. B.; Ferreira, R. A. N.

2017-09-01

In nuclear reactors, the performance of uranium dioxide (UO2) fuel is strongly dependent on the thermal conductivity, which directly affects the fuel pellet temperature, the fission gas release and the fuel rod mechanical behavior during reactor operation. The use of additives to improve UO2 fuel performance has been investigated, and beryllium oxide (BeO) appears as a suitable additive because of its high thermal conductivity and excellent chemical compatibility with UO2. In this paper, UO2-BeO pellets were manufactured by mechanical mixing, pressing and sintering processes varying the BeO contents and compaction pressures. Pellets with BeO contents of 2 wt%, 3 wt%, 5 wt% and 7 wt% BeO were pressed at 400 MPa, 500 MPa and 600 MPa. The laser flash method was applied to determine the thermal diffusivity, and the results showed that the thermal diffusivity tends to increase with BeO content. Comparing thermal diffusivity results of UO2 with UO2-BeO pellets, it was observed that there was an increase in thermal diffusivity of at least 18 % for the UO2-2 wt% BeO pellet pressed at 400 MPa. The maximum relative expanded uncertainty (coverage factor k = 2) of the thermal diffusivity measurements was estimated to be 9 %.

VOCs Emissions from Multiple Wood Pellet Types and Concentrations in Indoor Air

PubMed Central

Soto-Garcia, Lydia; Ashley, William J.; Bregg, Sandar; Walier, Drew; LeBouf, Ryan; Hopke, Philip K.; Rossner, Alan

2016-01-01

Wood pellet storage safety is an important aspect for implementing woody biomass as a renewable energy source. When wood pellets are stored indoors in large quantities (tons) in poorly ventilated spaces in buildings, such as in basements, off-gassing of volatile organic compounds (VOCs) can significantly affect indoor air quality. To determine the emission rates and potential impact of VOC emissions, a series of laboratory and field measurements were conducted using softwood, hardwood, and blended wood pellets manufactured in New York. Evacuated canisters were used to collect air samples from the headspace of drums containing pellets and then in basements and pellet storage areas of homes and small businesses. Multiple peaks were identified during GC/MS and GC/FID analysis, and four primary VOCs were characterized and quantified: methanol, pentane, pentanal, and hexanal. Laboratory results show that total VOCs (TVOCs) concentrations for softwood (SW) were statistically (p < 0.02) higher than blended or hardwood (HW) (SW: 412 ± 25; blended: 203 ± 4; HW: 99 ± 8, ppb). The emission rate from HW was the fastest, followed by blended and SW, respectively. Emissions rates were found to range from 10−1 to 10−5 units, depending upon environmental factors. Field measurements resulted in airborne concentrations ranging from 67 ± 8 to 5000 ± 3000 ppb of TVOCs and 12 to 1500 ppb of aldehydes, with higher concentrations found in a basement with a large fabric bag storage unit after fresh pellet delivery and lower concentrations for aged pellets. These results suggest that large fabric bag storage units resulted in a substantial release of VOCs into the building air. Occupants of the buildings tested discussed concerns about odor and sensory irritation when new pellets were delivered. The sensory response was likely due to the aldehydes. PMID:27022205

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

PubMed

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

Phosphorus recovery using pelletized adsorptive materials ...

EPA Pesticide Factsheets

Phosphorous (P) is one of the essential nutrients for growth and is generally the most limiting nutrient since, it cannot be fixed from the atmosphere. Methods for recovering phosphorous from water systems already exist, but advances are being made to find a more economic, efficient, effective and easy to use method that can allow for reuse of the recovered P. One area of study is in adsorption, which involves finding the best material for adsorption of phosphorous from water and for releasing it back into the environment through desorption or leaching. The goal of this research was to first optimize the capacity for a pelletized adsorptive material that was synthesized with varying amounts of a binder material from 0-20 % and then to study recovering the phosphate for reuse. The pelletized materials were studied through kinetics experiments as well as isotherm experiments to gain insight into the adsorption capacity and mechanism. Following successful adsorption, a simple leaching study was conducted to see how much phosphate would be released back into water without any added desorption aid. Desorption was then studied by changing the pH of solution. Presenting my thesis work with a poster at ACS.

Blood, sweat, tears and success of technology transfer long-term controlled-release of herbicides: Root-growth-inhibiting biobarrier technology

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

Van Voris, P.; Cataldo, D.A.; Burton, F.G.

Through the unique combination of polymers with a herbicidally active dinitroaniline, a cylinderical pellet (9mm long and 9mm in diameter) was developed that continuously releases a herbicide for a period of up to 100 years. Equilibrium concentration of the herbicide in soil adjacent to the pellet and the bioactive lifetime of the device cam be adjusted by changing the size of the pellet; the type of polymer; the type, quality, and quantity of carrier; and/or the concentration and type of dinitroaniline used. Commercial products that have been developed under a Federal Technology Transfer Program that utilize this technology include: (1)more » ROOT-SHIELD, a root repelling sewer gasket for concrete, clay, and PVC sewer lines, (2) BIOBARRIER, a spun-bonded polypropylene geotextile fabric developed to prevent root growth from invading septic tanks; penetrating under roadways, and along the edge of sidewalks, airport runways, and tennis courts, and for landscaped areas; and (3) ROOT-GUARD, a plastic drip irrigation emitter designed to protect buried drip irrigation systems from being plugged by roots. 17 refs., 4 figs., 6 tabs.« less

Development and demonstration of a lignite-pelletizing process. Phase II report

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

Not Available

1980-01-01

The current work began with scale-up of laboratory equipment to commercial size equipment. For this purpose, BCI used an existing pilot plant that had been assembled to pelletize and indurate taconite ore. BCI determined therewith that lignite pellets can be produced continuously on a pilot scale using the basic process developed in the laboratory. The resulting pellets were found to be similar to the laboratory pellets at equivalent binder compositions. Tests of product made during a 5-ton test run are reported. A 50-ton demonstration test run was made with the pilot plant. Pellet production was sustained for a two-week period.more » The lignite pelletizing process has, therefore, been developed to the point of demonstration in a 50-ton test. BCI has completed and cost estimated a conceptually designed 4000 TPD facility. BCI believes it has demonstrated a technically feasible process to agglomerate lignite by using an asphalt emulsion binder. Product quality is promising. Capital and operating costs appear acceptable to justify continuing support and development. The next step should focus on three areas: production development, process refinement, and cost reduction. For further development, BCI recommends consideration of a 5 to 10 ton/h pilot plant or a 20 to 40 ton/h module of a full sized plant, the lower first cost of the former being offset by the ability to incorporate the latter into a future production unit. Other specific recommendations are made for future study that could lead to process and cost improvements: Binder Formulation, disc Sizing, Drier Bed Depth, and Mixing Approach. Pellet use other than power plant fuel is considered.« less

Time-Series Similarity Analysis of Satellite Derived Data to Understand Changes in Forest Biomass.

NASA Astrophysics Data System (ADS)

Singh, N.; Fritz, B.

2017-12-01

One of the goals of promoting bioenergy is reducing green-house gas emissions by replacing fossil fuels. However, there are concerns that carbon emissions due to changes in land use resulting from crop production for ethanol will negate the impact of biofuels on the environment. So, the current focus is to use lignocellulose feedstocks also referred to as second generation biofuels as the new source of bioenergy. Wood based pellets derived from the forests of southeastern United States are one such source which is being exported to Europe as a carbon-neutral fuel. These wood-pellets meet the EU standard for carbon emissions and are being used to replace coal for energy generation and heating. As a result US exports of wood-based pellets have increased from nearly zero to over 6 million metric tons over the past 8 years. Wood-based pellets are traditionally produced from softwood trees which have a relatively shorter life-cycle and propagate easily, and thus are expected to provide a sustainable source of wood chips used for pellet production. However, there are concerns that as the demand and price of wood pellets increases, lumber mills will seek wood chips from other sources as well, particularly from hardwood trees resulting in higher carbon emissions as well as loss of biodiversity. In this study we use annual stacks of normalized difference vegetation index (NDVI) data at a 16-day temporal resolution to monitor biomass around pellet mills in southeastern United States. We use a combination of time series similarity technique and supervised learning to understand if there have been significant changes in biomass around pellet mills in the southeastern US. We also demonstrate how our method can be used to monitor biomass over large geographic regions using phenological properties of growing vegetation.

Glass-bonded iodosodalite waste form for immobilization of 129 I

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

Chong, Saehwa; Peterson, Jacob A.; Riley, Brian J.

Immobilization of radioiodine (e.g., 129I, 131I) is an important need for current and future nuclear fuel cycles. For the current work, iodosodalite [Na8(AlSiO4)6I2] was synthesized hydrothermally from metakaolin, NaI, and NaOH. Following hydrothermal treatment, dried unwashed powders were used to make glass-bonded iodosodalite waste forms by heating pressed pellets at 650, 750, or 850 °C with two different types of sodium borosilicate glass binders, i.e., NBS-4 and SA-800. These heat-treated specimens were characterized with X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, thermal analysis, porosity and density measurements, neutron activation analysis, and inductively-coupled plasma mass spectrometry. Themore » pellets mixed with 10 mass% of NBS-4 or SA-800 and heat-treated at 750 °C contained relatively high percentage iodine retention (~44-47 % of the maximum iodine loading) with relatively low porosities, while other pellets with higher percentages iodine retention either contained higher porosity or were not completely sintered. ASTM C1308 chemical durability tests of monolithic specimens showed a large initial release of Na, Al, Si, and I on the first day, possibly from water-soluble salt crystals or non-durable amorphous phases. Release rates of Na and Si were higher than for Al and I, probably due to a poorly durable Na-Si-O phase from the glass bonding matrix. The cumulative normalized release of iodine was 12.5 g m-2 for the first 10 1-d exchanges, suggestive of coherent dissolution. The average release rate from 10-24 days during the 7-d exchange intervals was 0.2336 g m-2 d-1.« less

Process and system for producing high-density pellets from a gaseous medium

DOEpatents

Foster, Christopher A.

1999-01-01

A process and system for producing pellets of high density carbon dioxide or other gases utilize a chamber containing a plurality of cell-like freezing compartments within which ice is to be formed. A gas desired to be frozen into ice is introduced into the chamber while the internal pressure of the chamber is maintained at a level which is below the equilibrium triple pressure of the gas. The temperature of the freezing compartments is lowered to a temperature which is below the equilibrium vapor pressure temperature of the gas at the chamber pressure so that the gas condenses into ice within the compartments. The temperature of the freezing compartments is thereafter raised so that the ice is thereby released from and falls out of the compartments as pellets for collection.

Energy-dependent expansion of .177 caliber hollow-point air gun projectiles.

PubMed

Werner, Ronald; Schultz, Benno; Bockholdt, Britta; Ekkernkamp, Axel; Frank, Matthias

2017-05-01

Amongst hundreds of different projectiles for air guns available on the market, hollow-point air gun pellets are of special interest. These pellets are characterized by a tip or a hollowed-out shape in their tip which, when fired, makes the projectiles expand to an increased diameter upon entering the target medium. This results in an increase in release of energy which, in turn, has the potential to cause more serious injuries than non-hollow-point projectiles. To the best of the authors' knowledge, reliable data on the terminal ballistic features of hollow-point air gun projectiles compared to standard diabolo pellets have not yet been published in the forensic literature. The terminal ballistic performance (energy-dependent expansion and penetration) of four different types of .177 caliber hollow-point pellets discharged at kinetic energy levels from approximately 3 J up to 30 J into water, ordnance gelatin, and ordnance gelatin covered with natural chamois as a skin simulant was the subject of this investigation. Energy-dependent expansion of the tested hollow-point pellets was observed after being shot into all investigated target media. While some hollow-point pellets require a minimum kinetic energy of approximately 10 J for sufficient expansion, there are also hollow-point pellets which expand at kinetic energy levels of less than 5 J. The ratio of expansion (RE, calculated by the cross-sectional area (A) after impact divided by the cross-sectional area (A 0 ) of the undeformed pellet) of hollow-point air gun pellets reached values up of to 2.2. The extent of expansion relates to the kinetic energy of the projectile with a peak for pellet expansion at the 15 to 20 J range. To conclude, this work demonstrates that the hollow-point principle, i.e., the design-related enlargement of the projectiles' frontal area upon impact into a medium, does work in air guns as claimed by the manufacturers.

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.

PubMed

Kendig, Derek M; Hurst, Norman R; Bradley, Zachary L; Mahavadi, Sunila; Kuemmerle, John F; Lyall, Vijay; DeSimone, John; Murthy, Karnam S; Grider, John R

2014-12-01

Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. Copyright © 2014 the American Physiological Society.

Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

PubMed Central

Kendig, Derek M.; Hurst, Norman R.; Bradley, Zachary L.; Mahavadi, Sunila; Kuemmerle, John F.; Lyall, Vijay; DeSimone, John; Murthy, Karnam S.

2014-01-01

Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5′-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1−/− mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. PMID:25324508

Chronomodulated drug delivery system of urapidil for the treatment of hypertension

PubMed Central

Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

2015-01-01

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. PMID:25838996

Sudden death in the presence of overt beta-adrenergic receptor activation in guinea pigs immediately following isoflurane anesthesia.

PubMed

Overholser, Brian R; Zheng, Xiaomei; Pell, Carrie; Blickman, Andrew

2010-05-01

A case series of sudden death is reported in five consecutive guinea pigs following anesthesia with inhalational isoflurane during beta-adrenergic receptor stimulation with isoproterenol. Sustained-release isoproterenol pellets or mini-osmotic pumps were implanted subcutaneously in male Dunkin-Hartley guinea pigs as part of a research study to assess the interplay of adrenergic receptor activation and the development of atrial arrhythmias. The continuous exposure to isoproterenol resulted in a similar presentation and eventual sudden death in all guinea pigs exposed to inhalational isoflurane between 15 to 40 minutes after discontinuation of anesthesia. Death occurred in guinea pigs in this case series despite the fact that doses of isoproterenol used were more than 10-fold lower than previously reported in guinea pigs in the absence of isoflurane anesthesia. The cause of death was suspected to be due to an interaction of isoproterenol with isoflurane anesthesia, as placebo implantation or anesthesia alone did not result in cardiac arrest. Of four subsequent guinea pigs anesthetized with the combination of xylazine and ketamine (X/K), three survived isoproterenol implantation for the full 21-day study period while one died perioperatively. There was an increased rate of post-anesthetic mortality associated with isoproterenol pellet implantation in guinea pigs anesthetized with isoflurane compared to X/K. This may be due to the detrimental effects of the combination of isoflurane during overt beta-adrenergic receptor activation or cardioprotective effects of X/K anesthesia during beta-adrenergic receptor hyperactivity.

Adsorption characteristics of water vapor on gear-pellet and honeycomb-pellet types of adsorbents containing A-type zeolite

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

Nakamura, A.; Munakata, K.; Hara, K.

2015-03-15

It is necessary to recover or process tritiated species that are extensively coexistent in nuclear fusion installations. A conventional way to recover tritium release to atmosphere is catalytic oxidation of tritiated species and adsorption of tritiated water vapor on adsorbents with high surface areas. Therefore, new adsorbents with low pressure loss and high surface areas need to be developed and utilized for such large-scale adsorption systems. In this study, attention was focused on new adsorbents, which are gear-type pellet MS5A adsorbent, gear-type pellet MS4A adsorbent and honeycomb-type pellet MS5A adsorbent. The adsorption characteristics of the new adsorbent were comparatively studiedmore » with conventional type of adsorbents (pellet-type MS5A adsorbent and pebble-type MS5A adsorbent), in terms of adsorption capacity, pressure loss and adsorption rate. It was found that the adsorption capacity of water vapor on the gear-type adsorbents is higher than that on a honeycomb-type adsorbent. The experimental breakthrough curves indicate that the adsorption rates of water vapor on gear-type and honeycomb-type adsorbents are smaller than that on conventional type adsorbents. Various adsorption models were also tested to correlate the experimental isotherms. It was found that the Langmuir-Freundlich model could properly correlate the experimental adsorption isotherms.« less

[Left ventricular projectile migration after an accidental close-range gunshot wound].

PubMed

Driessen, A; Tjardes, T; Eikermann, C; Trojan, S; Fröhlich, M; Grimaldi, G; Kosse, N

2016-07-01

We report the case of a 24-year-old female after sustaining a shotgun wound in the left upper extremity and chest. Initial emergency diagnostics revealed numerous shotgun pellets scattered throughout the left-side soft tissue, chest and upper lung lobe with one pellet having migrated into the left ventricle of the heart.Due to the devastating injury pattern, gunshot wounds are interdisciplinarily challenging and should include extended initial diagnostics, such as contrast agent CT. The potential toxicity of elevated lead blood levels have to be taken into further account.

Medical consequences of terrorist bombs containing spherical metal pellets: analysis of a suicide terrorism event.

PubMed

Kluger, Yoram; Mayo, Ami; Hiss, Jehuda; Ashkenazi, Eitamar; Bendahan, Jose; Blumenfeld, Amir; Michaelson, Moshe; Stein, Michael; Simon, Daniel; Schwartz, Ivan; Alfici, Ricardo

2005-02-01

Various metal objects added to explosives increase and diversify the wounding from bombing; especially favoured are spherical missiles for their special injuring characteristics. Our objective was to study the medical consequences and ballistic effects on human tissue of spherical metal pellets used in terrorist bombings. The clinical and forensic data of all bodily injured casualties of a suicide terrorist bombing in a crowded hotel dining room were analysed retrospectively. Of the 250 people at the scene, 164 were injured, with 91 (55.5%) suffering bodily injuries; 30 of them died. The immediately deceased had disseminated tissue damage and their bodies were saturated with steel spheres. Thirty-two immediate survivors sustained severe injuries (Injury Severity Score > or =16), and all suffered tissue penetration by the pellets. Twenty-three (32%) underwent surgery and 15 (21%) required intensive care. Metal pellets propelled by the explosion enhanced the secondary pattern of injury and injured even patients remote from the origin. Tissue destruction and specific organ injuries among survivors were limited. To evaluate and manage victims of terrorist bombings properly, medical teams should become familiar with these severe injuries.

Sustainable thermoelectric materials fabricated by using Cu2Sn1-xZnxS3 nanoparticles as building blocks

NASA Astrophysics Data System (ADS)

Zhou, Wei; Shijimaya, Chiko; Takahashi, Mari; Miyata, Masanobu; Mott, Derrick; Koyano, Mikio; Ohta, Michihiro; Akatsuka, Takeo; Ono, Hironobu; Maenosono, Shinya

2017-12-01

Uniform Cu2Sn1-xZnxS3 (x = 0-0.2) nanoparticles (NPs) with a characteristic size of about 40 nm were chemically synthesized. The primary crystal phase of the NPs was wurtzite (WZ) with a mean crystalline size of about 20 nm. The NPs were sintered to form nanostructured pellets with different compositions preserving the composition and grain size of the original NPs by the pulse electric current sintering technique. The pellets had a zinc blende (ZB) structure with a residual WZ phase, and the mean crystalline size was found to remain virtually unchanged for all pellets. Among all samples, the pellets of Cu2Sn0.95Zn0.05S3 and Cu2Sn0.85Zn0.15S3 exhibited the highest ZT value (0.37 at 670 K) which is 10 times higher than that of a non-nanostructured Cu2SnS3 bulk crystal thanks to effective phonon scattering by nanograins, the phase-pure ZB crystal structure, and the increase in hole carrier density by Zn doping.

Development of a Tritium Extruder for ITER Pellet Injection

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

M.J. Gouge; P.W. Fisher

As part of the International Thermonuclear Experimental Reactor (ITER) plasma fueling development program, Oak Ridge National Laboratory (ORNL) has fabricated a pellet injection system to test the mechanical and thermal properties of extruded tritium. Hydrogenic pellets will be used in ITER to sustain the fusion power in the plasma core and may be crucial in reducing first-wall tritium inventories by a process of "isotopic fueling" in which tritium-rich pellets fuel the burning plasma core and deuterium gas fuels the edge. This repeating single-stage pneumatic pellet injector, called the Tritium-Proof-of-Principle Phase II (TPOP-II) Pellet Injector, has a piston-driven mechanical extruder andmore » is designed to extrude and accelerate hydrogenic pellets sized for the ITER device. The TPOP-II program has the following development goals: evaluate the feasibility of extruding tritium and deuterium-tritium (D-T) mixtures for use in future pellet injection systems; determine the mechanical and thermal properties of tritium and D-T extrusions; integrate, test, and evaluate the extruder in a repeating, single-stage light gas gun that is sized for the ITER application (pellet diameter -7 to 8 mm); evaluate options for recycling propellant and extruder exhaust gas; and evaluate operability and reliability of ITER prototypical fueling systems in an environment of significant tritium inventory that requires secondary and room containment systems. In tests with deuterium feed at ORNL, up to 13 pellets per extrusion have been extruded at rates up to 1 Hz and accelerated to speeds of 1.0 to 1.1 km/s, using hydrogen propellant gas at a supply pressure of 65 bar. Initially, deuterium pellets 7.5 mm in diameter and 11 mm in length were produced-the largest cryogenic pellets produced by the fusion program to date. These pellets represent about a 10% density perturbation to ITER. Subsequently, the extruder nozzle was modified to produce pellets that are almost 7.5-mm right circular cylinders. Tritium and D-T pellets have been produced in experiments at the Los Alamos National Laboratory Tritium Systems Test Assembly. About 38 g of tritium have been utilized in the experiment. The tritium was received in eight batches, six from product containers and two from the Isotope Separation System. Two types of runs were made: those in which the material was only extruded and those in which pellets were produced and fired with deuterium propellant. A total of 36 TZ runs and 28 D-T runs have been made. A total of 36 pure tritium runs and 28 D-T mixture runs were made. Extrusion experiments indicate that both T2 and D-T will require higher extrusion forces than D2 by about a factor of two.« less

[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.

Influence of target thickness on the release of radioactive atoms

NASA Astrophysics Data System (ADS)

Guillot, Julien; Roussière, Brigitte; Tusseau-Nenez, Sandrine; Barré-Boscher, Nicole; Borg, Elie; Martin, Julien

2017-03-01

Nowadays, intense exotic beams are needed in order to study nuclei with very short half-life. To increase the release efficiency of the fission products, all the target characteristics involved must be improved (e.g. chemical composition, dimensions, physicochemical properties such as grain size, porosity, density…). In this article, we study the impact of the target thickness. Released fractions measured from graphite and uranium carbide pellets are presented as well as Monte-Carlo simulations of the Brownian motion.

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

PubMed

Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

2015-12-01

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Red Light-enhanced Phytochrome Pelletability

PubMed Central

Pratt, Lee H.; Marmé, Dieter

1976-01-01

Red light-enhanced pelletability of phytochrome was observed in extracts of all 11 plants tested: Avena sativa L., Secale cereale L., Zea mays L., Cucurbita pepo L., Sinapis alba L., Pisum sativum L., Helianthus anuus L., Raphanus sativus L., Glycine max (L.) Merr., Phaseolus vulgaris L., and Lupinus albus L. This enhanced pelletability was observed in all 11 plants following in situ irradiation (in vivo binding) but only in Sinapis and Cucurbita after irradiation of crude extracts (in vitro binding). In vivo binding was not strongly dependent upon pH and, with few exceptions, was not markedly sensitive to high salt concentration, whereas in vitro binding was completely reversed by both high pH and high salt concentration. However, both binding phenomena were observed only with a divalent cation in the extract buffer. In vivo binding was further characterized using Avena which showed an increase in pelletability from less than 10% in dark control extracts to more than 60% in extracts of red light-irradiated shoots. The half-life for binding was 40 seconds at 0.5 C and was strongly temperature-dependent, binding being complete within 5 to 10 sec at 22 C. If pelletable phytochrome in the far red-absorbing form was photoconverted back to the red-absorbing form in situ, phytochrome was released from the pelletable condition with a half-life of 25 minutes at 25 C and 100 minutes at both 13 C and 3 C. No cooperativity in red light-enhanced pelletability with respect to phytochrome-far red-absorbing form was observed. PMID:16659745

Modeling the effects of pelleting on the logistics of distillers grains shipping.

PubMed

Rosentrater, Kurt A; Kongar, Elif

2009-12-01

The energy security needs of energy importing nations continue to escalate. It is clear that biofuels can help meet some of the increasing need for energy. Theoretically, these can be produced from a variety of biological materials, including agricultural residues (such as corn stover and wheat straw), perennial grasses, legumes, algae, and other biological materials. Currently, however, the most heavily utilized material is corn starch. Industrial fuel ethanol production in the US primarily uses corn, because it is readily converted into fuel at a relatively low cost compared to other biomass sources. The production of corn-based ethanol in the US is dramatically increasing. As the industry continues to grow, the amount of byproducts and coproducts also increases. At the moment, the nonfermentable residues (which are dried and sold as distillers dried grains with solubles--DDGS) are utilized only as livestock feed. The sale of coproducts provides ethanol processors with a substantial revenue source and significantly increases the profitability of the production process. Even though these materials are used to feed animals in local markets, as the size and scope of the industry continues to grow, the need to ship large quantities of coproducts grows as well. This includes both domestic as well as international transportation. Value-added processing options offer the potential to increase the sustainability of each ethanol plant, and thus the industry overall. However, implementation of new technologies will be dependent upon how their costs interact with current processing costs and the logistics of coproduct deliveries. The objective of this study was to examine some of these issues by developing a computer model to determine potential cost ramifications of using various alternative technologies during ethanol processing. This paper focuses specifically on adding a densification unit operation (i.e., pelleting) to produce value-added DDGS at a fuel ethanol manufacturing plant. We have examined the economic implications of pelleting DDGS for varying DDGS production rates (100-1000 tons/d) and pelleting rates (0-100%), for a series of DDGS sales prices ($50-$200/ton). As the proportion of pelleting increases, the cost of transporting DDGS to distant markets drastically declines, because the rail cars can be filled to capacity. For example, at a DDGS sales price of $50/ton, 100% pelleting will reduce shipping costs (both direct and indirect) by 89% compared to shipping the DDGS in bulk form (i.e., no pelleting), whereas at a DDGS sales price of $200/ton, it will reduce costs by over 96%. It is clear that the sustainability of the ethanol industry can be improved by implementing pelleting technology for the coproducts, especially at those plants that ship their DDGS via rail.

Fabrication of (U,Am)O2 pellet with controlled porosity from oxide microspheres

NASA Astrophysics Data System (ADS)

Ramond, Laure; Coste, Philippe; Picart, Sébastien; Gauthé, Aurélie; Bataillea, Marc

2017-08-01

U1-xAmxO2±δ mixed-oxides are considered as promising compounds for americium heterogeneous transmutation in Sodium Fast Neutron Reactor. Porous microstructure is envisaged in order to facilitate helium and fission gas release and to reduce pellet swelling during irradiation and under self-irradiation. In this study, the porosity is created by reducing (U,Am)3O8 microspheres into (U,Am)O2 during the sintering. This reduction is accompanied by a decrease of the lattice volume that leads to the creation of open porosity. Finally, an (U0.90Am0.10)O2 porous ceramic pellet (D∼89% of the theoretical density TD) with controlled porosity (≥8% open porosity) was obtained from mixed-oxide microspheres obtained by the Weak Acid Resin (WAR) process.

Influence of firebed temperature on inorganic particle emissions in a residential wood pellet boiler

NASA Astrophysics Data System (ADS)

Gehrig, Matthias; Jaeger, Dirk; Pelz, Stefan K.; Weissinger, Alexander; Groll, Andreas; Thorwarth, Harald; Haslinger, Walter

2016-07-01

The temperature-dependent release of inorganic elements is the first step of the main formation pathway of particle emissions in automatically fired biomass burners. To investigate this step, a residential pellet boiler with an underfeed-burner was equipped with a direct firebed cooling. This test setup enabled decreased firebed temperatures without affecting further parameters like air flow rates or oxygen content in the firebed. A reduction of particle emissions in PM1-fraction at activated firebed cooling was found by impactor measurement and by optical particle counter. The affected particles were found in the size range <0.3 μm and have been composed mainly of potassium chloride (KCl). The chemical analysis of PM1 and boiler ash showed no statistically significant differences due to the firebed cooling. Therefore, our results indicate that the direct firebed cooling influenced the release of potassium (K) without affecting other chemical reactions.

ESR studies on the influence of physiological dissolution and digestion media on the lipid phase characteristics of SEDDS and SEDDS pellets.

PubMed

Abdalla, Ahmed; Mäder, Karsten

2009-02-09

The aim of the current study is the evaluation of a recently optimized SEDDS, composed of Solutol HS15 and medium chain glycerides, and self-emulsifying pellets by means of ESR. Tempol-benzoate (TB)-loaded SEDDS were produced and electron spin resonance (ESR) spectroscopy was used to evaluate the diluted self-emulsifying mixtures. Moreover, ESR in vitro digestion experiments were carried out to have an insight on the characteristics of the different phases formed during the digestion process and to evaluate the distribution and the localization of TB in these phases. In addition, self-emulsifying pellets were produced using nitroxide-loaded SEDDS and the microenvironment within the pellets during release process was monitored in an online process using ESR spectroscopy. After dilution of nitroxide-loaded SEDDS, the percent of TB localized in the lipophilic compartment was decreasing with increasing the surfactant fraction in the mixture. Moreover, it was found that different phases with variable viscosity and polarity were produced as a result of the enzymatic digestion of SEDDS in physiologically relevant media. This change in lipid composition has largely affected the distribution and the localization of the spin probe during the digestion process. A rapid increase in the mobility of the spin probe inside the pellets was noticed after exposure to the release media. Additionally, TB was localized within the self-emulsifying mixture environment for the time of the experiment. ESR is considered a powerful non-invasive tool to assess the microenvironment of the diluted SEDDS and to monitor in vitro digestion process. Digestion induces a change in lipid composition which can affect the solubilization capacity of the administered drug. Therefore, monitoring in vitro digestion process using ESR spectroscopy will help in providing greater understanding of the interaction between the administered drug and the digested lipid vehicles.

Administration of CREON® pancrelipase pellets via gastrostomy tube is feasible with no loss of gastric resistance or lipase activity: an in vitro study.

PubMed

Shlieout, George; Koerner, Andreas; Maffert, Mario; Forssmann, Kristin; Caras, Steven

2011-01-01

In clinical practice, the need sometimes arises to administer pancreatic enzyme replacement therapy via gastrostomy tube (G-tube) by mixing the pellets contained in the capsules with soft food. The objective of this study was to identify G-tubes that allow administration of pancrelipase gastro-resistant pellets without clogging, sticking, pellet damage or loss of enteric coating integrity. In this in vitro study, CREON® (pancrelipase) Delayed-Release Capsules were opened and the pellets sprinkled onto a small amount of baby food of pH <4.5 (applesauce and bananas manufactured by both Gerber and Beech-Nut). The mixture was stirred gently and after 15 minutes poured into a 35 mL syringe and pushed slowly (~15 mL in 10-15 seconds) through a G-tube. Pellets were collected and the tube flushed with water. G-tubes were inspected visually for clogging/sticking and damage to pellets was assessed. If there was none with all four foods, pellet integrity (gastric resistance and lipase activity) was assessed by an in vitro dissolution method with a 2-hour gastric simulation step. The activity required to confirm integrity was ≥80% of actual US Pharmacopeia lipase activity per capsule. G-tubes initially tested were Kimberly-Clark MIC Bolus® size 14 French (Fr) and upwards and Kimberly-Clark MIC-KEY® 14 Fr and upwards. Following successful testing, assessment of Bard® Tri-Funnel 18 Fr and Bard® Button 18 Fr G-tubes was carried out. Based on the absence of clogging, sticking and visible damage to pellets, and the maintenance of pellet integrity, administration of CREON® pancrelipase pellets was feasible through the following G-tubes: Kimberly-Clark MIC Bolus® size 18 Fr, Kimberly-Clark MIC-KEY® 16 Fr, Bard® Tri-Funnel 18 Fr and Bard® Button 18 Fr. Lipase activity met the predetermined specification and was ≥90% for all four tubes and all four foods, with no differences versus untreated pellets (i.e. pellets not mixed with baby food or pushed through a G-tube). These data apply to all CREON® pancrelipase capsule formulations, regardless of their strength in lipase units, as pellet composition, size and quality are identical. CREON® pancrelipase pellets can be mixed with baby food of pH <4.5 and administered via the following G-tubes without clogging, sticking or visible pellet damage, and with no loss of gastric resistance or lipase activity: Kimberly-Clark MIC Bolus® size 18 Fr and larger, Kimberly-Clark MIC-KEY® 16 Fr and larger, Bard® Tri-Funnel 18 Fr and larger and Bard® Button 18 Fr and larger.

Core Fueling of DEMO by Direct Line Injection of High-Speed Pellets From the HFS

DOE PAGES

Frattolillo, Antonio; Baylor, Larry R.; Bombarda, Francesca; ...

2018-04-17

Pellet injection represents to date the most realistic candidate technology for core fueling of a demonstration fusion power reactor tokamak fusion reactor. Modeling of both pellet penetration and fuel deposition profiles, for different injection locations, indicates that effective core fuelling can be achieved launching pellets from the inboard high field side at speeds not less than ~ 1 km/s. Inboard pellet fueling is commonly achieved in present tokamaks, using curved guide tubes; however, this technology might be hampered at velocities ≥ 1 km/s. An innovative approach, aimed at identifying suitable inboard "direct line'' paths, to inject high-speed pellets (in themore » 3 to 4 km/s range), has recently been proposed as a potential complementary solution. The fuel deposition profiles achievable by this approach have been explored using the HPI2 simulation code. The results presented here show that there are possible geometrical schemes providing good fueling performance. The problem of neutron flux in a direct line-of-sight injection path is being investigated, though preliminary analyses indicate that, perhaps, this is not a serious problem. The identification and integration of straight injection paths suitably tilted may be a rather difficult task due to the many constraints and to interference with existing structures. The suitability of straight guide tubes to reduce the scatter cone of high-speed pellets is, therefore, of main interest. A preliminary investigation, aimed at addressing these technological issues, has recently been started. As a result, a possible implementation plan, using an existing Italian National Agency for New Technologies, Energy and Sustainable Economic Development-Oak Ridge National Laboratory facility is shortly outlined.« less

Core Fueling of DEMO by Direct Line Injection of High-Speed Pellets From the HFS

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

Frattolillo, Antonio; Baylor, Larry R.; Bombarda, Francesca

Pellet injection represents to date the most realistic candidate technology for core fueling of a demonstration fusion power reactor tokamak fusion reactor. Modeling of both pellet penetration and fuel deposition profiles, for different injection locations, indicates that effective core fuelling can be achieved launching pellets from the inboard high field side at speeds not less than ~ 1 km/s. Inboard pellet fueling is commonly achieved in present tokamaks, using curved guide tubes; however, this technology might be hampered at velocities ≥ 1 km/s. An innovative approach, aimed at identifying suitable inboard "direct line'' paths, to inject high-speed pellets (in themore » 3 to 4 km/s range), has recently been proposed as a potential complementary solution. The fuel deposition profiles achievable by this approach have been explored using the HPI2 simulation code. The results presented here show that there are possible geometrical schemes providing good fueling performance. The problem of neutron flux in a direct line-of-sight injection path is being investigated, though preliminary analyses indicate that, perhaps, this is not a serious problem. The identification and integration of straight injection paths suitably tilted may be a rather difficult task due to the many constraints and to interference with existing structures. The suitability of straight guide tubes to reduce the scatter cone of high-speed pellets is, therefore, of main interest. A preliminary investigation, aimed at addressing these technological issues, has recently been started. As a result, a possible implementation plan, using an existing Italian National Agency for New Technologies, Energy and Sustainable Economic Development-Oak Ridge National Laboratory facility is shortly outlined.« less

Efficacy of methoprene for mosquito control in storm water catch basins

USGS Publications Warehouse

Butler, M.; LeBrun, R.A.; Ginsberg, H.S.; Gettman, A.D.

2006-01-01

This study evaluated the efficacy of methoprene, a widely used juvenile hormone mimic, formulated as 30-day slow release Altosid? pellets, at controlling mosquitoes in underground storm water drainage catch basins. Data from applications to ?-sized cement catch basins in the laboratory, field observations from treated and untreated basins, and an experiment that confined mosquito larvae in floating emergence jars in catch basins showed that methoprene effectively controlled mosquitoes for a month under field conditions and substantially longer under laboratory conditions when applied at a dose of 3.5 g pellets per average-sized catch basin.

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

PubMed

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

2010-03-01

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

Sustained release of corticosterone in rats affects reactivity, but does not affect habituation to immobilization and acoustic stimuli.

PubMed

Tanke, Marit A C; Fokkema, Dirk S; Doornbos, Bennard; Postema, Folkert; Korf, Jakob

2008-07-18

Depression is often preceded by stressful life events and accompanied with elevated cortisol levels and glucocorticoid resistance. It has been suggested that a major depressive disorder may result from impaired coping with and adaptation to stress. The question is whether or not hypothalamus-pituitary-adrenal (HPA)-axis dysfunction influences the process of adaptation. We examined the effect of a dysregulated HPA-axis on the adaptation to acoustic stimuli in rats with or without preceding restraint stress. HPA-axis function was altered via slow release of corticosterone (CORT, 90 mg) from subcutaneously implanted pellets for 7 or 14 days. The rate of body temperature increases during restraint (10 min) and the response to acoustic stimuli (of 80+120 dB) were used to quantify daily stress reactivity. Rats habituated to either stress regardless of CORT treatment. CORT treatment combined with restraint decreased the initial reactivity and the variability in response, but the rate of habituation was not influenced. These results show that suppressing normal HPA-axis function by chronic exposure to CORT does affect the course of habituation, but not habituation per se. This implies that altered HPA-axis function in depressed patients may not be causally related to stress coping, but instead may influence the course of the disorder.

From sport hunting to breeding success: Patterns of lead ammunition ingestion and its effects on an endangered raptor.

PubMed

Gil-Sánchez, José M; Molleda, Saray; Sánchez-Zapata, José A; Bautista, Jesús; Navas, Isabel; Godinho, Raquel; García-Fernández, Antonio J; Moleón, Marcos

2018-02-01

Lead is highly toxic for wildlife, with pernicious consequences especially in long-lived predators. The causes of lead ammunition ingestion in Bonelli's eagle (Aquila fasciata) and its effects on breeding success were studied in one of the most important populations of this endangered species in Europe. Regurgitated pellets belonging to different pairs from 2004 to 2014 were analyzed, both in the breeding (1363 pellets from 12 territories) and non-breeding (172 pellets from 9 territories) seasons. From these territories, 57 molted feathers to study lead contamination were analyzed, and breeding success was monitored for 41 breeding attempts. The occurrence of lead shots in pellets was detected using X-ray photographs. Pellets were also used to describe eagle diet. Lead shots in pellets were present in 83.3% of the territories. The frequency of occurrence of lead shots in pellets (2.81% in spring and 1.31% in autumn) was primarily related to the consumption of red-legged partridge in the breeding season (when partridges are hunted from blinds using calling lures), and secondarily to rabbit consumption in the non-breeding season (coinciding with the main hunting season). Thus, our results indicate that injured small-game were the main source of lead contamination in the Bonelli's eagle. For the first time for a raptor species, a positive relationship between the frequency of occurrence of lead shots in pellets and lead concentration in eagles' feathers has been documented. Lead concentration in feathers (mean±SD: 816±426μgkg -1 , with no sex-related differences) was high for a species that rarely eats carrion or aquatic birds (the main prey-related lead source for raptors). This had negative effects on breeding success, which could jeopardize Bonelli's eagles in other European populations that are sustained by juvenile dispersal from the study population. Our work shows that some game modalities pose a potential threat to endangered raptors. Copyright © 2017 Elsevier B.V. All rights reserved.

Recycling of MSWI fly ash by means of cementitious double step cold bonding pelletization: Technological assessment for the production of lightweight artificial aggregates.

PubMed

Colangelo, Francesco; Messina, Francesco; Cioffi, Raffaele

2015-12-15

In this work, an extensive study on the recycling of municipal solid waste incinerator fly ash by means of cold bonding pelletization is presented. The ash comes from an incineration plant equipped with rotary and stoker furnaces, in which municipal, hospital and industrial wastes are treated. Fly ash from waste incineration is classified as hazardous and cannot be utilized or even landfilled without prior treatment. The pelletization process uses cement, lime and coal fly ash as components of the binding systems. This process has been applied to several mixes in which the ash content has been varied from 50% (wt.%) up to a maximum of 70%. An innovative additional pelletization step with only cementitious binder has been performed in order to achieve satisfactory immobilization levels. The obtained lightweight porous aggregates are mostly suitable for recovery in the field of building materials with enhanced sustainability properties. Density, water absorption and crushing strength ranged from 1000 to 1600 kg/m(3), 7 to 16% and 1.3 to 6.2 MPa, respectively, and the second pelletization step increased stabilization efficiency. The feasibility of the process has been analyzed by testing also concrete specimens containing the artificial aggregates, resulting in lightweight concrete of average performance. Copyright © 2015 Elsevier B.V. All rights reserved.

Moisture plasticization for enteric Eudragit® L30D-55-coated pellets prior to compression into tablets.

PubMed

Rujivipat, Soravoot; Bodmeier, Roland

2012-05-01

Enteric polymers such as cellulose esters (cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate) and methacrylic acid-acrylate copolymers (Eudragit® L100-55 and S100) are quite brittle in the dry state and thus not suitable as pellet coatings for compression into tablets. The objective of this study was to investigate the role of humidity treatment for moisture plasticization in order to successfully compress the enterically coated pellets. The mechanical properties of Eudragit® L100-55 improved dramatically, while the properties of the other enteric polymers showed only minor changes after storage at higher humidity. The significant increase in flexibility of the Eudragit® L film was caused by hydration/plasticization; its elongation value changed from approx. 3% in the dry state to approx. 140% at the higher storage humidity. Storage at 84% relative humidity resulted in comparable release profiles of compressed and uncompressed pellets. The glass transition temperature of Eudragit® L films decreased below the compression temperature (room temperature) at storage humidities between 75% and 84%. The glass transition relative humidity leading to a change from the glassy to the rubbery state was determined by dynamic vapor sorption (DVS) to be 76.8%. Moisture resulted in superior plasticization for Eudragit® L than the conventional plasticizer triethyl citrate. The improved compressibility of high humidity treated Eudragit® L-coated pellets was also shown with single pellet compression data as indicated by an increased crushing force and deformation. In conclusion, moisture plasticization was a highly effective tool to enable the successful compression of pellets coated with the brittle enteric polymer Eudragit® L. Copyright © 2012 Elsevier B.V. All rights reserved.

Characteristics of waste automotive glasses as silica resource in ferrosilicon synthesis.

PubMed

Farzana, Rifat; Rajarao, Ravindra; Sahajwalla, Veena

2016-02-01

This fundamental research on end-of-life automotive glasses, which are difficult to recycle, is aimed at understanding the chemical and physical characteristics of waste glasses as a resource of silica to produce ferrosilicon. Laboratory experiments at 1550°C were carried out using different automotive glasses and the results compared with those obtained with pure silica. In situ images of slag-metal separation showed similar behaviour for waste glasses and silica-bearing pellets. Though X-ray diffraction (XRD) showed different slag compositions for glass and silica-bearing pellets, formation of ferrosilicon was confirmed. Synthesized ferrosilicon alloy from waste glasses and silica were compared by Raman, X-ray photoelectron spectroscopy and scanning electron microscopy (SEM) analysis. Silicon concentration in the synthesized alloys showed almost 92% silicon recovery from the silica-bearing pellet and 74-92% silicon recoveries from various waste glass pellets. The polyvinyl butyral (PVB) plastic layer in the windshield glass decomposed at low temperature and did not show any detrimental effect on ferrosilicon synthesis. This innovative approach of using waste automotive glasses as a silica source for ferrosilicon production has the potential to create sustainable pathways, which will reduce specialty glass waste in landfill. © The Author(s) 2015.

Apparatus for unloading nuclear fuel pellets from a sintering boat

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

Bucher, G.D.; Raymond, T.E.

1987-02-10

An apparatus is described for unloading nuclear fuel pellets from a loaded sintering boat having an open top, comprising: (a) means for receiving the boat in an upright position with the pellets contained therein, the boat receiving means including a platform for supporting the loaded boat in the upright position, the boat supporting platform having first and second portions; (b) means for clamping the boat including a pair of plates disposed at lateral sides of the boat and being movable in a first direction relative to one another for applying clamping forces to the boat on the platform and inmore » a second direction relative to one another for releasing the clamping forces from the boat. The pair of plates have inner surfaces facing toward one another, the first and second platform portions of the boat supporting platform being mounted to the plates on the respective facing surfaces thereof and disposed in a common plane. One of the plates and one of the platform portions mounted thereto are disposed in a stationary position and the other of the plates and the other of the platform portions mounted thereto are movable relative thereto in the first and second directions for applying and releasing clamping forces to and from the boat while the boat is supported in the upright position by the platform portions; (c) means for transferring the clamped boat from the upright position to an inverted position and then back to the upright position; and (d) means of receiving the pellets from the clamped boat as the boat is being transferred from the upright position to the inverted position.« less

Inoculation of female American black bears (Ursus americanus) with partially purified porcine zona pellucidae limits cub production.

PubMed

Lane, V M; Liu, I K M; Casey, K; vanLeeuwen, E M G; Flanagan, D R; Murata, K; Munro, C

2007-01-01

The present 2-year study investigated the feasibility of using porcine zona pellucidae (pZP) as antigen for immunocontraception in American black bears. Sows, 3-6 years of age, were administered either two doses of 250 microg pZP with Freund's adjuvant (n = 10) or adjuvant alone (n = 5), one in April and one in May, and were kept away from the boars until June. Serum samples were collected before injections and before denning (November). The presence of sows with cubs at side was observed during premature emergence from denning. First-year results indicated that anti-pZP antibody titres in vaccinated sows were 2.5-9.0-fold (range) higher compared with non-vaccinated sows and that the vaccinated sows were threefold less likely to become pregnant (P = 0.167). Control and vaccinated bears produced 1.6 and 0.2 cubs per sow, respectively (P = 0.06). The second-year study investigated the feasibility of using pZP sequestered in a controlled-release pellet and a water-soluble adjuvant (QS-21) to avoid regulatory problems associated with Freund's adjuvant. Sows in the treatment group (n = 22) were administered a single dose of an emulsion of 250 microg pZP and 150 microg QS-21 plus a pellet containing 70-90 microg pZP for delayed release as booster dose. Control sows (n = 5) received the QS-21 adjuvant in pellet alone. Serum samples were collected before inoculations (April) and before denning (November). Seven cubs were born to the five control sows, but none was born to the 22 vaccinated sows (P < 0.001). Anti-pZP antibody mean absorbance ratios in control sows remained at background levels, whereas vaccinated sows had ratios fourfold higher than controls. Two-dimensional polyacrylamide gel electrophoresis and immunohistochemical localisation confirmed immunoreactivity of sera from inoculated bears. We conclude that cub production in the American black bear can be effectively limited with either two injections of 250 microg pZP or a single inoculation of partially purified pZP sequestered in controlled-release pellets.

3D Printed Antibiotic and Chemotherapeutic Eluting Catheters for Potential Use in Interventional Radiology: In Vitro Proof of Concept Study.

PubMed

Weisman, Jeffery A; Ballard, David H; Jammalamadaka, Udayabhanu; Tappa, Karthik; Sumerel, Jan; D'Agostino, Horacio B; Mills, David K; Woodard, Pamela K

2018-05-22

Additive manufacturing may be used as a form of personalized medicine in interventional radiology by allowing for the creation of customized bioactive constructs such as catheters that can act as a form of localized drug delivery. The purpose of the present in vitro study was to use three-dimensional (3D) printing to construct bioactive-laden bioabsorbable catheters impregnated with antibiotics and chemotherapeutics. Polylactic acid bioplastic pellets were coated with the powdered bioactive compounds gentamicin sulfate (GS) or methotrexate (MTX) to incorporate these drugs into the 3D printed constructs. The pellets were then extruded into drug-impregnated filament for fused deposition modeling 3D printing. Computer-aided design files were generated in the shapes of 14-F catheters. Scanning electron microscope imaging was used to visualize the presence of the additive powders on the surface of the printed constructs. Elution profiles were run on the antibiotic-laden catheter and MTX-laden catheters. Antibiotic-laden catheters were tested on bacterial broth and plate cultures. Both GS and MTX catheter constructs had sustained drug release up to the 5-day limit of testing. The 3D printed GS-enhanced catheters inhibited all bacterial growth in broth cultures and had an average zone of inhibition of 858 ± 118 mm 2 on bacterial plates, whereas control catheters had no effect. The 3D printing manufacturing method to create instruments in percutaneous procedures is feasible. Further in vivo studies will substantiate these findings. Copyright © 2018. Published by Elsevier Inc.

Protonic and Electronic Charge Carriers in Solvated Biomacromolecules

DTIC Science & Technology

1989-01-01

samples with sufficient mechanical strength. The pellets were approximately one millimeter thick and were placed between two platinium foil...attached to the vacuum line, Figure 2, by simply tilting them. The platinium electrodes were blocking for protons so all protonic carriers were released

Effects of Sustained Avoidance/Escape on Demand for Food

DTIC Science & Technology

1991-01-01

Escape Economics Feeding Circadian rhythms Rats SINCE sustained performance under aversive conditions is con- was demonstrated in a study in which...pigeons received food for sidered to be stressful for humans, and stress is a factor in the pecking at a key that alternated between white and red. each...manipulation was carried out both early (day 3 or day 5) or late animals (2). In these studies , a single 45 mg food pellet was (day 21 or day 23) after the

Dynamic leaching studies of 48 MWd/kgU UO2 commercial spent nuclear fuel under oxic conditions

NASA Astrophysics Data System (ADS)

Serrano-Purroy, D.; Casas, I.; González-Robles, E.; Glatz, J. P.; Wegen, D. H.; Clarens, F.; Giménez, J.; de Pablo, J.; Martínez-Esparza, A.

2013-03-01

The leaching of a high-burn-up spent nuclear fuel (48 MWd/KgU) has been studied in a carbonate-containing solution and under oxic conditions using a Continuously Stirred Tank Flow-Through Reactor (CSTR). Two samples of the fuel, one prepared from the centre of the pellet (labelled CORE) and another one from the fuel pellet periphery, enriched with the so-called High Burn-Up Structure (HBS, labelled OUT) have been used.For uranium and actinides, the results showed that U, Np, Am and Cm gave very similar normalized dissolution rates, while Pu showed slower dissolution rates for both samples. In addition, dissolution rates were consistently two to four times lower for OUT sample compared to CORE sample.Considering the fission products release the main results are that Y, Tc, La and Nd dissolved very similar to uranium; while Cs, Sr, Mo and Rb have up to 10 times higher dissolution rates. Rh, Ru and Zr seemed to have lower dissolution rates than uranium. The lowest dissolution rates were found for OUT sample.Three different contributions were detected on uranium release, modelled and attributed to oxidation layer, fines and matrix release.

[Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

PubMed

Ise, Yuya; Wako, Tetsuya; Miura, Yoshihiko; Katayama, Shirou; Shimizu, Hisanori

2009-12-01

The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

The effect of biomass densification on structural sugar release and yield in biofuel feedstock and feedstock blends

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

Wolfrum, Edward J.; Nagle, Nicholas J.; Ness, Ryan M.

In this work, we examined the behavior of feedstock blends and the effect of a specific feedstock densification strategy (pelleting) on the release and yield of structural carbohydrates in a laboratory-scale dilute acid pretreatment (PT) and enzymatic hydrolysis (EH) assay. We report overall carbohydrate release and yield from the two-stage PT-EH assay for five single feedstocks (two corn stovers, miscanthus, switchgrass, and hybrid poplar) and three feedstock blends (corn stover-switchgrass, corn stover-switchgrass-miscanthus, and corn stover-switchgrass-hybrid poplar). We first examined the experimental results over time to establish the robustness of the PT-EH assay, which limits the precision of the experimental results.more » The use of two different control samples in the assay enabled us to identify (and correct for) a small bias in the EH portion of the combined assay for some runs. We then examined the effect of variable pretreatment reaction conditions (residence time, acid loading, and reactor temperature) on the conversion of a single feedstock (single-pass corn stover, CS-SP) in order to establish the range of pretreatment reaction conditions likely to provide optimal conversion data. Finally, we applied the assay to the 16 materials (8 feedstocks in 2 formats, loose and pelleted) over a more limited range of pretreatment experimental conditions. The four herbaceous feedstocks behaved similarly, while the hybrid poplar feedstock required higher pretreatment temperatures for optimal results. As expected, the yield data for three blended feedstocks were the average of the yield data for the individual feedstocks. As a result, the pelleting process appears to provide a slightly positive effect on overall total sugar yield.« less

The effect of biomass densification on structural sugar release and yield in biofuel feedstock and feedstock blends

DOE PAGES

Wolfrum, Edward J.; Nagle, Nicholas J.; Ness, Ryan M.; ...

2017-01-13

In this work, we examined the behavior of feedstock blends and the effect of a specific feedstock densification strategy (pelleting) on the release and yield of structural carbohydrates in a laboratory-scale dilute acid pretreatment (PT) and enzymatic hydrolysis (EH) assay. We report overall carbohydrate release and yield from the two-stage PT-EH assay for five single feedstocks (two corn stovers, miscanthus, switchgrass, and hybrid poplar) and three feedstock blends (corn stover-switchgrass, corn stover-switchgrass-miscanthus, and corn stover-switchgrass-hybrid poplar). We first examined the experimental results over time to establish the robustness of the PT-EH assay, which limits the precision of the experimental results.more » The use of two different control samples in the assay enabled us to identify (and correct for) a small bias in the EH portion of the combined assay for some runs. We then examined the effect of variable pretreatment reaction conditions (residence time, acid loading, and reactor temperature) on the conversion of a single feedstock (single-pass corn stover, CS-SP) in order to establish the range of pretreatment reaction conditions likely to provide optimal conversion data. Finally, we applied the assay to the 16 materials (8 feedstocks in 2 formats, loose and pelleted) over a more limited range of pretreatment experimental conditions. The four herbaceous feedstocks behaved similarly, while the hybrid poplar feedstock required higher pretreatment temperatures for optimal results. As expected, the yield data for three blended feedstocks were the average of the yield data for the individual feedstocks. As a result, the pelleting process appears to provide a slightly positive effect on overall total sugar yield.« less

Extraction of Organochlorine Pesticides from Plastic Pellets and Plastic Type Analysis.

PubMed

Pflieger, Marilyne; Makorič, Petra; Kovač Viršek, Manca; Koren, Špela

2017-07-01

Plastic resin pellets, categorized as microplastics (≤5 mm in diameter), are small granules that can be unintentionally released to the environment during manufacturing and transport. Because of their environmental persistence, they are widely distributed in the oceans and on beaches all over the world. They can act as a vector of potentially toxic organic compounds (e.g., polychlorinated biphenyls) and might consequently negatively affect marine organisms. Their possible impacts along the food chain are not yet well understood. In order to assess the hazards associated with the occurrence of plastic pellets in the marine environment, it is necessary to develop methodologies that allow for rapid determination of associated organic contaminant levels. The present protocol describes the different steps required for sampling resin pellets, analyzing adsorbed organochlorine pesticides (OCPs) and identifying the plastic type. The focus is on the extraction of OCPs from plastic pellets by means of a pressurized fluid extractor (PFE) and on the polymer chemical analysis applying Fourier Transform-InfraRed (FT-IR) spectroscopy. The developed methodology focuses on 11 OCPs and related compounds, including dichlorodiphenyltrichloroethane (DDT) and its two main metabolites, lindane and two production isomers, as well as the two biologically active isomers of technical endosulfan. This protocol constitutes a simple and rapid alternative to existing methodology for evaluating the concentration of organic contaminants adsorbed on plastic pieces.

Fluidized bed combustion of pelletized biomass and waste-derived fuels

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

Chirone, R.; Scala, F.; Solimene, R.

2008-10-15

The fluidized bed combustion of three pelletized biogenic fuels (sewage sludge, wood, and straw) has been investigated with a combination of experimental techniques. The fuels have been characterized from the standpoints of patterns and rates of fuel devolatilization and char burnout, extent of attrition and fragmentation, and their relevance to the fuel particle size distribution and the amount and size distribution of primary ash particles. Results highlight differences and similarities among the three fuels tested. The fuels were all characterized by limited primary fragmentation and relatively long devolatilization times, as compared with the time scale of particle dispersion away frommore » the fuel feeding ports in practical FBC. Both features are favorable to effective lateral distribution of volatile matter across the combustor cross section. The three fuels exhibited distinctively different char conversion patterns. The high-ash pelletized sludge burned according to the shrinking core conversion pattern with negligible occurrence of secondary fragmentation. The low-ash pelletized wood burned according to the shrinking particle conversion pattern with extensive occurrence of secondary fragmentation. The medium-ash pelletized straw yielded char particles with a hollow structure, resembling big cenospheres, characterized by a coherent inorganic outer layer strong enough to prevent particle fragmentation. Inert bed particles were permanently attached to the hollow pellets as they were incorporated into ash melts. Carbon elutriation rates were very small for all the fuels tested. For pelletized sludge and straw, this was mostly due to the shielding effect of the coherent ash skeleton. For the wood pellet, carbon attrition was extensive, but was largely counterbalanced by effective afterburning due to the large intrinsic reactivity of attrited char fines. The impact of carbon attrition on combustion efficiency was negligible for all the fuels tested. The size distribution of primary ash particles liberated upon complete carbon burnoff largely reflected the combustion pattern of each fuel. Primary ash particles of size nearly equal to that of the parent fuel were generated upon complete burnoff of the pelletized sludge. Nonetheless, secondary attrition of primary ash from pelletized sludge is large, to the point where generation of fine ash would be extensive over the typical residence time of bed ash in fluidized bed combustors. Very few and relatively fine primary ash particles were released after complete burnoff of wood pellets. Primary ash particles remaining after complete burnoff of pelletized straw had sizes and shapes that were largely controlled by the occurrence of ash agglomeration phenomena. (author)« less

Development of a regenerable system employing silica-titania composites for the recovery of mercury from end-box exhaust at a chlor-alkali facility.

PubMed

Stokke, Jennifer M; Mazyck, David W

2008-04-01

The release of mercury to the environment is of particular concern because of its volatility, persistence, and tendency to bioaccumulate. The recovery of mercury from end-box exhaust at chlor-alkali facilities is important to prevent release into the environment and reduce emissions as required by NESHAP (National Emission Standards for Hazardous Air Pollutants). A pilot-scale photocatalytic reactor packed with silica-titania composite (STC) pellets was tested at a chloralkali facility over a 3-month period. This pilot reactor treated up to 10 ft3/min (ACFM) of end-box exhaust and achieved 95% removal. The pilot reactor was able to maintain excellent removal efficiency even with large fluctuations in influent mercury concentration (400-1600 microg/ft3). The STC pellets were regenerated ex situ by regeneration with hydrochloric acid and performed similarly to virgin STC pellets when returned to service. On the basis of these promising results, two full-scale reactors with in situ regeneration capabilities were installed and operated. After optimization, these reactors performed similarly to the pilot reactor. A cost analysis was performed comparing the treatment costs (i.e., cost per pound of mercury removed) for sulfur-impregnated activated carbon and the STC system. The STC proved to be both technologically and economically feasible for this installation.

21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethazine sustained-release tablets. 520....2260c Sulfamethazine sustained-release tablets. (a) Sponsor. See No. 053501 in § 510.600(c) of this chapter for use of an 8-gram sulfamethazine sustained-release tablet. (b) Conditions of use—(1) Amount. 8...

Comparison of low-shear and high-shear granulation processes: effect on implantable calcium phosphate granule properties.

PubMed

Chevalier, E; Viana, M; Cazalbou, S; Chulia, D

2009-10-01

Calcium phosphate porous ceramics present a great interest not only as complex bone defect fillers but also as drug delivery systems. Most of the methods described in the literature to fabricate pellets are based on compaction, casting into spherical molds, or on processes such as liquid immiscibility or foaming. Despite wet granulation is used in a wide range of applications in pharmaceuticals, food, detergents, fertilizers, and minerals, it is not applied in the biomaterial field to produce granules. In this study physicochemical and in vitro drug delivery properties of implantable calcium phosphate granules, produced by two wet agglomeration processes, were compared. Pellets obtained by high shear granulation (granulation in a Mi-Pro apparatus) were shown to be more spherical and less friable than granules elaborated by low shear process (granulation in a Kenwood apparatus). Although Mi-Pro pellets had a slightly lower porosity compared to Kenwood granules, ibuprofen loading efficiency and dissolution profiles were not statistically different and the release mechanism was mainly controlled by diffusion, in both cases. Mi-Pro pellets appeared to be better candidates as bone defect fillers and local drug delivery systems as far as they were more spherical and less friable than Kenwood agglomerates.

Fatal laryngeal oedema in an adult from an air rifle injury, and related ballistics.

PubMed

Radojevic, Nemanja; Cukic, Dragana; Curovic, Ivana; Golubovic, Mileta

2015-01-01

Air guns (air pistols and rifles) are already recognized as being potentially lethal. The diabolo pellet has a calibre of .177 (4.5 mm), a 1250 fps velocity, is high energetic, and is most commonly used in such weapons. In the presented case, the victim sustained an air rifle injury to the neck. The pellet passed through the thyroid cartilage, subsequently causing the extensive laryngeal swelling with haematoma around the pellet channel which fatally obstructed the airway. It is estimated microscopically that at least a number of hours must have passed from the injury to the time of death. For this case, a shooting distance was estimated by using experimental shooting values compared to physics formulas for accelerated motion. The case under question has confirmed an applicable legal approach that can be utilized by countries to classify air rifles as being as harmful as other firearms, especially those with high muzzle velocities. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Status and prospects for renewable energy using wood pellets from the southeastern United States

DOE PAGES

Dale, Virginia H.; Kline, Keith L.; Parish, Esther S.; ...

2017-04-20

The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, 'How is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?' To addressmore » this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Furthermore, long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management.« less

Status and prospects for renewable energy using wood pellets from the southeastern United States

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

Dale, Virginia H.; Kline, Keith L.; Parish, Esther S.

The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, 'How is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?' To addressmore » this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Furthermore, long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management.« less

Modeling the Local Ecological Response to Regional Landscape and Global Change Forcings: A Case Study of Bioenergy in North Carolina, USA

NASA Astrophysics Data System (ADS)

Terando, A. J.; Costanza, J. K.; Tarr, N. M.; Apt, R.; Rubino, M. J.

2015-12-01

Sustainable energy policies in Europe have led to a growing market for bioenergy, and especially wood pellets, as a means to reduce fossil fuel emissions and the attendant socio-environmental consequences from climate change. However the introduction of this market has the potential to create significant negative ecological impacts whose costs are borne far from Europe. Because of its existing forest products infrastructure and resources, the Southeast US is viewed as an attractive supplier of wood pellets to Europe. Consequently, a new global telecoupling has developed between these two regions linking the natural capital of one region to the energy needs and greenhouse gas abatement policy of the other. Additionally, habitat for many important wildlife species in the Southeast lie within a rapidly urbanizing region characterized by low-density auto-dependent growth. Combined, these two forcings have the potential to rapidly degrade species-rich ecosystems. Here the ecological effects of increased European demand for wood pellets are examined in North Carolina. Future land use and vegetation change were projected using the results from linked urbanization, vegetation dynamics, life cycle analysis, and forest timber economics models. Ecological impacts as measured for 16 amphibian and avian species were evaluated under five bioenergy production scenarios and one urbanization-only scenario. Results indicate that highly vagile or upland species are able to take advantage of the increase in vegetated land cover, even if the majority of new habitat is in intensively managed forests. Conversely, more sessile and range-limited species, particularly those found in coastal plain systems such as bottomland hardwood forest, show steeper declines under the wood pellet scenarios than under the urbanization-only scenario. These results highlight the challenge of evaluating the sustainability of developing markets that seek to mitigate certain aspects of global environmental change but risk exacerbating others.

An Investigation of the Sub-Microsecond Features of Dynamic Crack Propagation in PMMA and the Rdx-Based Explosive PBX 9205

NASA Astrophysics Data System (ADS)

Washabaugh, P. D.; Hill, L. G.

2007-12-01

A dynamic crack propagating in a brittle material releases enough thermal energy to produce visible light. The dynamic fracture of even macroscopically amorphous materials becomes unsteady as the crack propagation velocity approaches the material wave-speeds. The heat generated at a crack-tip, especially as it jumps, may be a mechanism to initiate a self-sustaining reaction in an energetic material. Experiments were conducted in specimens to simulate an infinite plate for ˜10 μs. The initial specimens were 152 mm square by 6 mm thick acrylic sheets, and were fabricated to study non-steady near-wave-speed crack propagation. A variant of this specimen embedded a 25 mm×3 mm PBX 9205 pellet to explore the influence of dynamic Mode-I cracks in these materials. The crack was initiated by up to 0.24 g of Detasheet placed along a precursor 50 mm long notch, with a shield to contain the reaction products and prevent propagation along the fractured surfaces. The crack was studied by means of a streak camera and a Fourier-filter of the light reflecting off the newly minted surfaces. The sub-microsecond behavior of holes initiating, preceding and coalescing with the main crack were observed in the PMMA samples. The embedding and mechanical loading of explosives by this technique did not initiate a self-sustaining reaction in preliminary testing.

An initial investigation of the sub-microsecond features of dynamic crack propagation in PMMA and the RDX-based explosive PBX 9205

NASA Astrophysics Data System (ADS)

Washabaugh, Peter; Hill, Larry

2007-06-01

A dynamic crack propagating in a brittle material releases enough thermal energy to produce visible light. The dynamic fracture of even macroscopically amorphous materials becomes unsteady as the crack propagation velocity approaches the material wave-speeds. The heat generated at a crack-tip, especially as it jumps, may be a mechanism to initiate a self-sustaining reaction in an energetic material. Experiments were conducted in specimens to simulate an infinite plate for 20 μs. The initial specimens were 152 mm square by 6 mm thick acrylic sheets, and were fabricated to study non-steady near-wave-speed crack propagation. A variant of this specimen embedded a 25 mm x 3 mm PBX 9205 pellet to explore the influence of dynamic Mode-I cracks in these materials. The crack was initiated by up to 0.2 g of Detasheet placed along a precursor 50 mm long notch, with a shield to contain the reaction products and prevent propagation along the fractured surfaces. The crack was studied by means of a streak camera and a Fourier-filter of the light reflecting off the newly minted surfaces. The sub-microsecond behavior of holes initiating, preceding and coalescing with the main crack were observed in the PMMA samples. The embedding and mechanical loading of explosives by this technique did not initiate a self-sustaining reaction in preliminary testing.

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan.

PubMed

El Maghraby, Gamal M; Elzayat, Ehab M; Alanazi, Fars K

2012-08-01

Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping. Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine. Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release. Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product. Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.

Supplementation of alfalfa (Medicago sativa) with condensed tannin-containing pellets of sericea lespedeza (Lespedeza cuneata): Effects on ruminant urinary urea excretion and digestibility

USDA-ARS?s Scientific Manuscript database

Some feedstuffs that contain condensed tannins can reduce urinary urea excretion without compromising nutrition for ruminant livestock. This results in reducing environmental impact, improving productivity and enhancing sustainability of ruminant farming operations. In some situations there are adva...

Harvesting of Chlorella sorokiniana by co-culture with the filamentous fungus Isaria fumosorosea: A potential sustainable feedstock for hydrothermal gasification.

PubMed

Mackay, Stephen; Gomes, Eduardo; Holliger, Christof; Bauer, Rolene; Schwitzguébel, Jean-Paul

2015-06-01

Despite recent advances in down-stream processing, production of microalgae remains substantially limited because of economical reasons. Harvesting and dewatering are the most energy-intensive processing steps in their production and contribute 20-30% of total operational cost. Bio-flocculation of microalgae by co-cultivation with filamentous fungi relies on the development of large structures that facilitate cost effective harvesting. A yet unknown filamentous fungus was isolated as a contaminant from a microalgal culture and identified as Isaria fumosorosea. Blastospores production was optimized in minimal medium and the development of pellets, possibly lichens, was followed when co-cultured with Chlorella sorokiniana under strict autotrophic conditions. Stable pellets (1-2mm) formed rapidly at pH 7-8, clearing the medium of free algal cells. Biomass was harvested with large inexpensive filters, generating wet slurry suitable for hydrothermal gasification. Nutrient rich brine from the aqueous phase of hydrothermal gasification supported growth of the fungus and may increase the process sustainability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of a fast, lean and agile direct pelletization process using experimental design techniques.

PubMed

Politis, Stavros N; Rekkas, Dimitrios M

2017-04-01

A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were spheronized using melted gelucire 50-13 as a binding material (BM). Experimentation was performed sequentially; a fractional factorial design was set up initially to screen the factors affecting the process, namely spray rate, quantity of BM, rotor speed, type of rotor disk, lubricant-glidant presence, additional spheronization time, powder feeding rate and quantity. From the eight factors assessed, three were further studied during process optimization (spray rate, quantity of BM and powder feeding rate), at different ratios of the solid mixture of CW and HPMC K100M. The study demonstrated that the novel hot melt process is fast, efficient, reproducible and predictable. Therefore, it can be adopted in a lean and agile manufacturing setting for the production of flexible pellet dosage forms with various release rates easily customized between immediate and modified delivery.

High-fat diet exacerbates bone loss in mice implanted with low-dose slow-release lipopolysaccharide pellets

USDA-ARS?s Scientific Manuscript database

Obesity is associated with chronic up-regulation of inflammatory cytokines which stimulate osteoclast activity and bone resorption. Osteopenia or low bone mass is observed in a variety of physiological conditions with chronic inflammation including aging and post-menopause with estrogen deficiency. ...

Line spectrum and ion temperature measurements from tungsten ions at low ionization stages in large helical device based on vacuum ultraviolet spectroscopy in wavelength range of 500-2200 Å.

PubMed

Oishi, T; Morita, S; Huang, X L; Zhang, H M; Goto, M

2014-11-01

Vacuum ultraviolet spectra of emissions released from tungsten ions at lower ionization stages were measured in the Large Helical Device (LHD) in the wavelength range of 500-2200 Å using a 3 m normal incidence spectrometer. Tungsten ions were distributed in the LHD plasma by injecting a pellet consisting of a small piece of tungsten metal and polyethylene tube. Many lines having different wavelengths from intrinsic impurity ions were observed just after the tungsten pellet injection. Doppler broadening of a tungsten candidate line was successfully measured and the ion temperature was obtained.

Line spectrum and ion temperature measurements from tungsten ions at low ionization stages in large helical device based on vacuum ultraviolet spectroscopy in wavelength range of 500–2200 Å

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

Oishi, T., E-mail: oishi@LHD.nifs.ac.jp; Morita, S.; Goto, M.

2014-11-15

Vacuum ultraviolet spectra of emissions released from tungsten ions at lower ionization stages were measured in the Large Helical Device (LHD) in the wavelength range of 500–2200 Å using a 3 m normal incidence spectrometer. Tungsten ions were distributed in the LHD plasma by injecting a pellet consisting of a small piece of tungsten metal and polyethylene tube. Many lines having different wavelengths from intrinsic impurity ions were observed just after the tungsten pellet injection. Doppler broadening of a tungsten candidate line was successfully measured and the ion temperature was obtained.

[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.

Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

PubMed

Barmpalexis, Panagiotis; Grypioti, Agni

2018-06-01

This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

Bilateral shotgun pellet pulmonary emboli

PubMed Central

Huebner, Stephen; Ali, Sayed

2012-01-01

Intravascular migration of bullets and other foreign bodies is a rare but known complication of penetrating trauma. Missile embolization can represent a diagnostic challenge because it may present in various and unexpected ways. We present the case of a 54-year-old female who sustained shotgun pellet emboli to the pulmonary arteries following a left upper extremity gunshot wound and related vascular surgery. The case illustrates bilateral embolization, and the embolic events occurred following surgery. Embolization should be considered in evaluating patients with gunshot wounds, particularly if there are anomalous symptoms or the projectile is not found in the original, or expected, location. Close attention to the location of the foreign bodies on serial radiographs may reveal the diagnosis of intravascular embolization. PMID:22690290

Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection.

PubMed

Liu, Xin; Xie, Zongping; Zhang, Changqing; Pan, Haobo; Rahaman, Mohamed N; Zhang, Xin; Fu, Qiang; Huang, Wenhai

2010-02-01

The objective of this work was to evaluate borate bioactive glass scaffolds (with a composition in the system Na(2)O-K(2)O-MgO-CaO-B(2)O(3)-P(2)O(5)) as devices for the release of the drug Vancomycin in the treatment of bone infection. A solution of ammonium phosphate, with or without dissolved Vancomycin, was used to bond borate glass particles into the shape of pellets. The in vitro degradation of the pellets and their conversion to a hydroxyapatite-type material in a simulated body fluid (SBF) were investigated using weight loss measurements, chemical analysis, X-ray diffraction, and scanning electron microscopy. The results showed that greater than 90% of the glass in the scaffolds degraded within 1 week, to form poorly crystallized hydroxyapatite (HA). Pellets loaded with Vancomycin provided controlled release of the drug over 4 days. Vancomycin-loaded scaffolds were implanted into the right tibiae of rabbits infected with osteomyelitis. The efficacy of the treatment was assessed using microbiological examination and histology. The HA formed in the scaffolds in vivo, resulting from the conversion of the glass, served as structure to support the growth of new bone and blood vessels. The results in this work indicate that bioactive borate glass could provide a promising biodegradable and bioactive material for use as both a drug delivery system and a scaffold for bone repair.

Shock Reactivity of Non-Porous Mixtures of Manganese and Sulfur

NASA Astrophysics Data System (ADS)

Jette, Francois-Xavier; Goroshin, Samuel; Higgins, Andrew

2007-06-01

Stoichiometric mixtures of manganese powder and sulfur were melt-cast into solid pellets in order to study the mechanism of shock-enhanced reactivity in non-porous heterogeneous mixtures. This mixture was selected due to the large exothermic heat release of the manganese-sulfur reaction (214 kJ/mol), which causes the reaction to be self-sustaining once initiated. The test samples were placed in planar recovery ampoules and a strong shock was delivered via the detonation of a charge of amine-sensitized nitromethane. Various shock strengths were achieved by placing different thicknesses of PMMA attenuator between the explosive charge and the ampoule. The results confirmed that shock-induced reactions can be produced in the absence of porosity. Indeed, the critical shock pressure that caused ignition of the mixture in the ampoule was found to be in the range 2.2 - 3.8 GPa (pressures were estimated using LS-DYNA simulations). In the cases where the shock was too weak to cause ignition in the ampoule, the sample was extracted and its ignition temperature was determined using a differential thermal analyzer.

Design and evaluation of self-nanoemulsifying pellets of repaglinide.

PubMed

Desai, N S; Nagarsenker, M S

2013-09-01

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

Bronchocarcinogenic properties of welding and thermal spraying fumes containing chromium in the rat.

PubMed

Berg, N O; Berlin, M; Bohgard, M; Rudell, B; Schütz, A; Warvinge, K

1987-01-01

The possible bronchocarcinogenic effects of fumes released during the shielded metal arc welding of stainless steel and the thermal spraying of chromium oxide (Cr2O3) have been studied on the rat. The fume particles were shown to contain tri- and hexavalent chromium in soluble and low soluble forms; they were collected and implanted as pellets in the bronchi of groups of 100 rats by the method of Laskin et al. A negative control group of 100 rats was included, as well as positive controls receiving pellets containing benz(a)pyrene. The experiment was continued for 34 months; no differences of biological significance were noted between the growth rates, survival times, and terminal organ weights of the test and negative control groups. At autopsy, the macroscopic and microscopic appearance of the organs in the three groups, including the local reaction to the implanted pellet, were similar. No precancerous changes were observed at the implantation sites; one rat, who received a pellet containing welding fumes, showed squamous cell carcinoma remote from the implantation site and not associated with the bronchus. It had the appearance of a metastasis. All three benz(a)pyrene control rats developed cancer at the implantation site. The occupational health implications of these findings are discussed.

Characterization of Residential Scale Biofuel Boilers and Fuels

NASA Astrophysics Data System (ADS)

Chandrasekaran, Sriraam R.

The objectives of this study were to: 1) characterize commercially available wood pellets and wood chips for basic properties such as calorific, ash, moisture contents; 2) analyze elements and ions and other possible contamination during the pellet manufacturing processes; 3) characterize the chemical and thermo-chemical property of grass pellets for their combustion potential; 4) characterize the emissions from 6 different residential scale boiler/furnace appliances burning grass and wood pellets; 5) characterize the emitted particulate matter for toxic and marker species with respect to combustion appliance and combustion conditions; and 6) determine the effects of the biomass fuel properties of 5 different grass pellets on particulate and gaseous emissions from a single type of boiler. The results from characterization of wood pellets and chips indicated that the wood pellet samples generally meet the quality standards. However, there are some samples that would fail the ash content requirements. Only the German standards have extensive trace element limits. Most of the samples would meet these standards, but some samples failed to meet these standards based on their lead, arsenic, cadmium, and copper concentrations. It is likely that inclusion of extraneous materials such as painted or pressure treated lumber led to the observed high concentrations. Given increasing use of pellets and chips as a renewable fuel, standards for the elemental composition of commercial wood pellets and chips are needed in United States to avoid the inclusion of extraneous materials. Such standards would reduce the environmental impact of toxic species that would be released when the wood is burned. Grass pellets were characterized for chemical and thermochemical properties. Switch grass pellets were studied for it thermal degradation process under inert and oxidizing atmosphere using TGA. The thermal degradation of grass pellet measured the activation energy and pre-exponential factors for switch grass decomposition. Two major losses occurred due to volatilization of cellulose, hemicelluloses, and lignin and burning or slow oxidation of residual char. The parameters were high for oxidative environment indicating high temperature sensitivity of the charcoal formation reaction. There was a substantial effect of heating rate on the mass loss and mass loss rate. The TG curve shifted to higher temperature ranges on increasing the heating rate. In both pyrolyzing and oxidizing conditions, average combustion and devolatlization rates increased. Emissions measurements and efficiency estimation were conducted on six commercially available residential scale appliances that utilize different technologies including direct combustion, gasification, lambda control, or fixed air flow rates that were designed to burn low ash wood (less than 1%). The grass has high ash and chlorine content producing more PM and chlorinated hydrocarbons including dioxins and furans. The results also indicated that the air supply and geometry of the furnace, and the type of furnace are also major influencing factors that affect the pollutant formation. To determine the effect of fuel properties on emissions formation, gaseous and particulate characterization was conducted of six fuels that include five different grass pellets types with ash content ranging from 3% to 13% and a premium wood pellet with ash content 0.6% on a boiler. Emissions from grass pellets were found to be higher than wood pellets and the PM; SO2 and NOx emissions were strongly related to the fuel properties such as ash content, sulfur and nitrogen content, respectively. CO emissions that indicate the completeness of reactions were higher for grass pellets and were strongly correlated to PAHs emissions. The PCDD/F emission was clearly a function of chlorine content of the fuel. A strong correlation existed between levoglucosan and PM2.5 concentrations indicated that levoglucosan is also a molecular marker for grass pellet combustion. All of the emissions were found to be higher for grass pellets when compared to the wood pellets and are higher at high loads than at low loads. These results show that the grass pellets cannot be used as a fuel in current generation wood pellet systems. It will be necessary to design systems that effectively deal with the higher ash and chlorine content if grass pellets are to be a significant fuel for home heating. (Abstract shortened by UMI.)

Pellet cladding mechanical interactions of ceramic claddings fuels under light water reactor conditions

NASA Astrophysics Data System (ADS)

Li, Bo-Shiuan

Ceramic materials such as silicon carbide (SiC) are promising candidate materials for nuclear fuel cladding and are of interest as part of a potential accident tolerant fuel design due to its high temperature strength, dimensional stability under irradiation, corrosion resistance, and lower neutron absorption cross-section. It also offers drastically lower hydrogen generation in loss of coolant accidents such as that experienced at Fukushima. With the implementation of SiC material properties to the fuel performance code, FRAPCON, performances of the SiC-clad fuel are compared with the conventional Zircaloy-clad fuel. Due to negligible creep and high stiffness, SiC-clad fuel allows gap closure at higher burnup and insignificant cladding dimensional change. However, severe degradation of SiC thermal conductivity with neutron irradiation will lead to higher fuel temperature with larger fission gas release. High stiffness of SiC has a drawback of accumulating large interfacial pressure upon pellet-cladding mechanical interactions (PCMI). This large stress will eventually reach the flexural strength of SiC, causing failure of SiC cladding instantly in a brittle manner instead of the graceful failure of ductile metallic cladding. The large interfacial pressure causes phenomena that were previously of only marginal significance and thus ignored (such as creep of the fuel) to now have an important role in PCMI. Consideration of the fuel pellet creep and elastic deformation in PCMI models in FRAPCON provide for an improved understanding of the magnitude of accumulated interfacial pressure. Outward swelling of the pellet is retarded by the inward irradiation-induced creep, which then reduces the rate of interfacial pressure buildup. Effect of PCMI can also be reduced and by increasing gap width and cladding thickness. However, increasing gap width and cladding thickness also increases the overall thermal resistance which leads to higher fuel temperature and larger fission gas release. An optimum design is sought considering both thermal and mechanical models of this ceramic cladding with UO2 and advanced high density fuels.

Relationship between gaseous N dynamics and the hydraulic state of hierarchically structured soils

NASA Astrophysics Data System (ADS)

Schlüter, Steffen; Dörsch, Peter; Vogel, Hans-Jörg

2017-04-01

The inherent spatial heterogeneity of soil generates spatially distributed micro-sites with different local N gas (NO, N2O, N2) production and release rates. Moreover, local micro-site conditions and the pathways between them depend on soil moisture which itself is highly dynamic close to the soil surface. These relationships need to be taken into account for a quantitative understanding of soil denitrification and associated N gas dynamics. Soil structure has been recognized as a key factor to understand the high spatial variability of N gas emissions. In particular gaseous N release from soils depends on: i) the total denitrification rate, which is related to the spatial extent and distribution of anaerobic sites and ii) the probability of N2O to escape from the soil without being further reduced to N2. This impact of soil structure is typically ignored in studies with soil slurries or repacked soil. In this project we run well-defined mesocosm experiments on N gas dynamics with hierarchically structured, artificial soils in which the spatial distribution of substrate and denitrifiers is known exactly. Sintered, porous glass pellets are inoculated with strains of Paracoccus denitrificans and/or Agrobacterium tumefaciens and amended with nutrient solution. These pellets are embedded in coarse-grained sand within gas-tight columns under O2/He atmosphere. The pellets are either places in layers or randomly to create different patterns of N gas production sites and diffusion pathways. Denitrification occurs in the anaerobic centers of the porous pellets, while the partially saturated sand matrix controls the diffusive transport of N gases towards the headspace, where all relevant gas concentrations are monitored with gas chromatography. Water saturations are adjusted such that the diffusive pathways are either fully continuous or partially discontinuous. Preliminary results indicate that the water content exert a major control on the magnitude of denitrification, whereas the onset and dynamics are mainly controlled by the position of the substrate and the denitrifiers.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PubMed

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

2016-01-01

The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Efficacy of tebuconazole embedded in biodegradable poly-3-hydroxybutyrate to inhibit the development of Fusarium moniliforme in soil microecosystems.

PubMed

Volova, Tatiana G; Prudnikova, Svetlana V; Zhila, Natalia O; Vinogradova, Olga N; Shumilova, Anna A; Nikolaeva, Elena D; Kiselev, Evgeniy G; Shishatskaya, Ekaterina I

2017-05-01

An important line of research is the development of a new generation of formulations with targeted and controlled release of the pesticide, using matrices made from biodegradable materials. In this study, slow-release formulations of the fungicide tebuconazole (TEB) have been prepared by embedding it into the matrix of poly-3-hydroxybutyrate (P3HB) in the form of films, microgranules and pellets. The average rates of P3HB degradation were determined by the geometry of the formulation, reaching, for 63 days, 0.095-0.116, 0.081-0.083 and 0.030-0.055 mg day -1 for films, microgranules and pellets respectively. The fungicidal activity of P3HB/TEB against the plant pathogen Fusarium moniliforme was compared with that of the commercial formulation Raxil Ultra. A pronounced fungicidal effect of the experimental P3HB/TEB formulations was observed in 2-4 weeks after application, and it was retained for 8 weeks, without affecting significantly the development of soil aboriginal microflora. TEB release can be regulated by the process employed to fabricate the formulation and the fungicide loading, and the TEB accumulates in the soil gradually, as the polymer is degraded. The experimental forms of TEB embedded in the slowly degraded P3HB can be used as a basis for developing slow-release fungicide formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Interfering with DNA Damage Signals: Radiosensitizing Prostate Cancer using Small Peptides

DTIC Science & Technology

2007-11-01

were pelleted, and a 25-l sample of the supernatant was analyzed for free phosphate in the malachite green assay by dilution with 100 l of a...developing solution ( malachite green). After incubation for 15 min, the release of phosphate was quantified by measuring the absorbance at 650 nm in a

Gamma-Ray Effects Testing in Lawrence Livermore National Laboratory’s Nova Upgrade Facility

DTIC Science & Technology

1992-03-01

However, the distribution of energy between neutrons and photons from the ICF pellet will be different then that from a thermonuclear bomb . In a...of the neutron energy to photons. Photons make up most of the energy released from a thermonuclear bomb (Glasstone, S., 1977:340-342). The neutrons

Multiple Irradiation Capsule Experiment (MICE)-3B Irradiation Test of Space Fuel Specimens in the Advanced Test Reactor (ATR) - Close Out Documentation for Naval Reactors (NR) Information

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

M. Chen; CM Regan; D. Noe

2006-01-09

Few data exist for UO{sub 2} or UN within the notional design space for the Prometheus-1 reactor (low fission rate, high temperature, long duration). As such, basic testing is required to validate predictions (and in some cases determine) performance aspects of these fuels. Therefore, the MICE-3B test of UO{sub 2} pellets was designed to provide data on gas release, unrestrained swelling, and restrained swelling at the upper range of fission rates expected for a space reactor. These data would be compared with model predictions and used to determine adequacy of a space reactor design basis relative to fission gas releasemore » and swelling of UO{sub 2} fuel and to assess potential pellet-clad interactions. A primary goal of an irradiation test for UN fuel was to assess performance issues currently associated with this fuel type such as gas release, swelling and transient performance. Information learned from this effort may have enabled use of UN fuel for future applications.« less

Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

NASA Astrophysics Data System (ADS)

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

2015-10-01

Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases.Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03029c

Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

PubMed

Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

2007-07-18

Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

PubMed Central

Gunjal, P. T.; Shinde, M. B.; Gharge, V. S.; Pimple, S. V.; Gurjar, M. K.; Shah, M. N.

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 32 full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:26798171

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology.

PubMed

Gunjal, P T; Shinde, M B; Gharge, V S; Pimple, S V; Gurjar, M K; Shah, M N

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3(2) full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

TECHNICAL SCOPE OF GAS-COOLED REACTOR FUEL ELEMENT IRRADIATION PROGRAM

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

None

A set of 55 experiments hss been outiined to provide a minimum irradiation program for selection of UO/sub 2/, pellet geometry and fabricntion techniques, and canning technology. These experiments fall into three catagories: prototype: untts in which radial dimension and heat fluxes sre close to proposed design values, but irradiation times are long; reduced-size prototype for accelerated tests in which most variables will be studied; and miniaurized pellet irradiation to obtain high burnup for fission gas release studies. Reactor space has been found generally available and several installations are now examining their capabilities to participate in the program. A tentativemore » schedule has been drawn to illustrate the feasibility of the program. (auth)« less

Material Science

NASA Image and Video Library

2004-07-12

This soldering iron has an evacuated copper capsule at the tip that contains a pellet of Bulk Metallic Glass (BMG) aboard the International Space Station (ISS). Prior to flight, researchers sealed a pellet of bulk metallic glass mixed with microscopic gas-generating particles into the copper ampoule under vacuum. Once heated in space, such as in this photograph, the particles generated gas and the BMG becomes a viscous liquid. The released gas made the sample foam within the capsule where each microscopic particle formed a gas-filled pore within the foam. The inset image shows the oxidation of the sample after several minutes of applying heat. Although hidden within the brass sleeve, the sample retained the foam shape when cooled, because the viscosity increased during cooling until it was solid.

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

Stone, J.P.; Holtsman, S.; Shellabarger, C.J.

Pellets containing 5 mg (/sup 3/H) diethylstilbestrol (DES) and 15 mg cholesterol were implanted S.C. in 84-day-old female Sprague-Dawley (S-D) and ACl rats. DES was released from the implanted pellets exponentially, and the release was not significantly different in S-D rats than in ACl rats. No mammary tumors developed in any treated or untreated S-D rats. In contrast, 90% of the DES-treated ACl rats developed mammary adenocarcinomas. A significant increase in the weight of the pituitary was noted in DES-treated ACl rats. The pituitarities of the treated ACl rats were 2 to 7 times as heavy as were controls, andmore » plasma prolactin levels were 10 to 40 times higher than in controls. In contrast, the pituitaries of treated S-D rats did not significantly increase in weight, and plasma prolactin levels were only 3 to 5 times higher than controls. The uteri of treated S-D rats were significantly heavier than those of control rats and contained large amounts of fluid. This effect was not seen in ACl rats. Although the release of DES from the implanted pellet was essentially the same in ACl and S-D rats, three distinctive strain differences in response to DES were noted: mammary adenocarcinomas were found only in treated ACl rats; pituitary prolactin-cell adenomas and associated elevated plasma prolactins levels were seen only in treated ACl rats; and pyometritis was induced only in treated S-D rats. Mammary adenocarcinomas and prolactin-cell adenoma responses in the treated ACl rats appear to be correlated with the increasing levels of plasma prolactin. This study demonstrates that the prolonged estrogen treatment of ACl and S-D female rats produces distinctly different mammary and pituitary neoplastic responses. This disparity in neoplastic responses appears to be reflected in the difference of degree to which the hypophysical prolactin cells are stimulated to grow and secrete hormone.« less

A Quality by Experimental Design Approach to Assess the Effect of Formulation and Process Variables on the Extrusion and Spheronization of Drug-Loaded Pellets Containing Polyplasdone® XL-10.

PubMed

Saripella, Kalyan K; Loka, Nikhil C; Mallipeddi, Rama; Rane, Anuja M; Neau, Steven H

2016-04-01

Successful pellet production has been reported in literature with cross-linked poly(vinylpyrrolidone), Polyplasdone® XL-10 and INF-10. In the present study, a quality by experimental design approach was used to assess several formulation and process parameter effects on the characteristics of Polyplasdone® XL-10 pellets, including pellet size, shape, yield, usable yield, friability, and number of fines. The hypothesis is that design of experiments and appropriate data analysis allow optimization of the Polyplasdone product. High drug loading was achieved using caffeine, a moderately soluble drug to allow in vitro release studies. A five-factor, two-level, half-fractional factorial design (Resolution V) with center point batches allowed mathematical modeling of the influence of the factors and their two-factor interactions on five of the responses. The five factors were Polyplasdone® level in the powder blend, volume of water in the wet massing step, wet mixing time, spheronizer speed, and spheronization time. Each factor and/or its two-factor interaction with another factor influenced pellet characteristics. The behavior of these materials under various processing conditions and component levels during extrusion-spheronization have been assessed, discussed, and explained based on the results. Numerical optimization with a desirability of 0.974 was possible because curvature and lack of fit were not significant with any of the model equations. The values predicted by the optimization described well the observed responses. The hypothesis was thus supported.

Skeletal response to corticosteroid deficiency and excess in growing male rats

NASA Technical Reports Server (NTRS)

Li, M.; Shen, Y.; Halloran, B. P.; Baumann, B. D.; Miller, K.; Wronski, T. J.

1996-01-01

The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not affect cortical bone mass. The results indicate that corticosteroid deficiency induces cancellous osteopenia, whereas supplementation with a near physiologic dose of the hormone prevents this bone loss in ADX rats. Furthermore, corticosteroid excess inhibits bone growth and bone turnover in a dose-dependent manner, but does not induce cancellous osteopenia in growing male rats.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

PubMed Central

Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed MA; Hassan, Omiya A

2016-01-01

Purpose The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Materials and methods Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). Conclusion The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. PMID:28008229

Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment.

PubMed

Torner, Luz; Plotsky, Paul M; Neumann, Inga D; de Jong, Trynke R

2017-03-01

The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

PubMed

Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

1988-01-01

The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels.

Variations in preenrichment pH of poultry feed and feed ingredients after incubation periods up to 48 hours

USDA-ARS?s Scientific Manuscript database

Salmonella sustains acid injury at about pH 4.0-5.0. Since most Salmonella present in feed and feed ingredients are already stressed by desiccation (and heat if pelleted), exposure to low pH may cause death and/or injury and result in contamination going undetected. The objective of this study was ...

Fabrication of simulated DUPIC fuel

NASA Astrophysics Data System (ADS)

Kang, Kweon Ho; Song, Ki Chan; Park, Hee Sung; Moon, Je Sun; Yang, Myung Seung

2000-12-01

Simulated DUPIC fuel provides a convenient way to investigate the DUPIC fuel properties and behavior such as thermal conductivity, thermal expansion, fission gas release, leaching, and so on without the complications of handling radioactive materials. Several pellets simulating the composition and microstructure of DUPIC fuel are fabricated by resintering the powder, which was treated through OREOX process of simulated spent PWR fuel pellets, which had been prepared from a mixture of UO2 and stable forms of constituent nuclides. The key issues for producing simulated pellets that replicate the phases and microstructure of irradiated fuel are to achieve a submicrometre dispersion during mixing and diffusional homogeneity during sintering. This study describes the powder treatment, OREOX, compaction and sintering to fabricate simulated DUPIC fuel using the simulated spent PWR fuel. The homogeneity of additives in the powder was observed after attrition milling. The microstructure of the simulated spent PWR fuel agrees well with the other studies. The leading structural features observed are as follows: rare earth and other oxides dissolved in the UO2 matrix, small metallic precipitates distributed throughout the matrix, and a perovskite phase finely dispersed on grain boundaries.

Formulation and Evaluation of Fixed-Dose Combination of Bilayer Gastroretentive Matrix Tablet Containing Atorvastatin as Fast-Release and Atenolol as Sustained-Release

PubMed Central

Dey, Sanjay; Chattopadhyay, Sankha; Mazumder, Bhaskar

2014-01-01

The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β-cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet. PMID:24527446

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics

PubMed Central

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2012-01-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:23960836

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

PubMed

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2013-04-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

A high-fat diet decreases bone mass in growing mice with systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide pellets

USDA-ARS?s Scientific Manuscript database

Chronic inflammation is linked to osteopenia or low bone mass, observed in a variety of physiological conditions such as aging and post-menopause with estrogen deficiency. Evidence suggests that obesity is also associated with low-grade chronic up-regulation of inflammatory cytokines. This study inv...

Adiabatic Shear - An Annotated Bibliography

DTIC Science & Technology

1974-07-01

A. Deformation Hardening/Softening B. Cryogenic Deformation C. Ductaity D. Plasticity !•-. Fracture F, Structure and Phase Transformation ...Structural changes and phase transformations are also noted. The Hiidden release of elastic stored energy, the high hydrostatic pressure, and the...crackintr increased with increasing pellet velocity. Slip without transformation was oliservcd in both the aluminum alloy and stainless steel plates

The relationship between mineral contents, particle matter and bottom ash distribution during pellet combustion: molar balance and chemometric analysis.

PubMed

Jeguirim, Mejdi; Kraiem, Nesrine; Lajili, Marzouk; Guizani, Chamseddine; Zorpas, Antonis; Leva, Yann; Michelin, Laure; Josien, Ludovic; Limousy, Lionel

2017-04-01

This paper aims to identify the correlation between the mineral contents in agropellets and particle matter and bottom ash characteristics during combustion in domestic boilers. Four agrifood residues with higher mineral contents, namely grape marc (GM), tomato waste (TW), exhausted olive mill solid waste (EOMSW) and olive mill wastewater (OMWW), were selected. Then, seven different pellets were produced from pure residues or their mixture and blending with sawdust. The physico-chemical properties of the produced pellets were analysed using different analytical techniques, and a particular attention was paid to their mineral contents. Combustion tests were performed in 12-kW domestic boiler. The particle matter (PM) emission was characterised through the particle number and mass quantification for different particle size. The bottom ash composition and size distribution were also characterised. Molar balance and chemometric analyses were performed to identify the correlation between the mineral contents and PM and bottom ash characteristics. The performed analyses indicate that K, Na, S and Cl are released partially or completely during combustion tests. In contrast, Ca, Mg, Si, P, Al, Fe and Mn are retained in the bottom ash. The chemometric analyses indicate that, in addition to the operating conditions and the pellet ash contents, K and Si concentrations have a significant effect on the PM emissions as well as on the agglomeration of bottom ash.

A role for microtubules in sorting endocytic vesicles in rat hepatocytes.

PubMed Central

Goltz, J S; Wolkoff, A W; Novikoff, P M; Stockert, R J; Satir, P

1992-01-01

The vectorial nature of hepatocyte receptor-mediated endocytosis (RME) and its susceptibility to cytoskeletal disruptors has suggested that a polarized network of microtubules plays a vital role in directed movement during sorting. Using as markers a well-known ligand, asialoorosomucoid, and its receptor, we have isolated endocytic vesicles that bind directly to and interact with stabilized endogenous hepatocyte microtubules at specific times during a synchronous, experimentally initiated, single wave of RME. Both ligand- and receptor-containing vesicles copelleted with microtubules in the absence of ATP but did not pellet under similar conditions when microtubules were not polymerized. When 5 mM ATP was added to preparations of microtubule-bound vesicles, ligand-containing vesicles were released into the supernatant, while receptor-containing vesicles remained immobilized on the microtubules. Release of ligand-containing vesicles from microtubules was prevented by monensin treatment during the endocytic wave. Several proteins, including the microtubule motor protein cytoplasmic dynein, were present in these preparations and were released from microtubule pellets by ATP addition concomitantly with ligand. These results suggest that receptor domains within the endosome can be immobilized by attachment to microtubules so that, following monensin-sensitive dissociation of ligand from receptor, ligand-containing vesicles can be pulled along microtubules away from the receptor domains by a motor molecule, such as cytoplasmic dynein, thereby delineating sorting. Images PMID:1353884

A study on the applicability of in-line measurements in the monitoring of the pellet coating process.

PubMed

Hudovornik, Grega; Korasa, Klemen; Vrečer, Franc

2015-07-30

Special populations including paediatric and elderly patients often need advanced approaches in treatment, such as one-a-day dosing, which is achieved with modified release formulations or alternative routes of applications such as nasogastric route. Pellets are a dosage form that is frequently used in such formulations. The aim of the present work was to study the applicability of two in-line techniques, namely, Near Infrared Spectroscopy (NIR) and Spatial Filtering Technique (SFT) in the pellet coating process. The first objective of our work was to develop a prediction model for moisture content determination with the in-line NIR and to test its robustness in terms of sensitivity to changes in composition of the pellets and performance in wide range of moisture content. Secondly, the in-line SFT measurement was correlated with different off-line particle size methods. The third objective was to evaluate the ability of both in-line techniques for the detection of undesired deviations during the process, such as pellet attrition and agglomeration. Finally, the ability to predict coating thickness with the in-line NIR probe was evaluated. Results suggested that NIR prediction model for moisture content was less robust outside the calibration range and was also sensitive to changes in composition of the film coating. Nevertheless, satisfactory prediction was achieved in the case when coating composition was partially altered and adequate calibration range was used. The SFT probe results were in good correlation with off-line particle size measurement methods and proved to be an effective tool for coating thickness determination during the coating, however, the probe failed to accurately show the actual amount of the agglomerates formed during the process. In experiment when pellet attrition was initiated, both probes successfully detected abrasion of the pellet surface in real time. Furthermore, a predictive NIR model for coating thickness was made and showed a good potential to measure coating thickness in-line, suggesting that the NIR probe can be used as a single tool to monitor water content, coating thickness, and deviations in the coating process. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of methods for glycogen analysis of in vitro fermentation pellets produced with strained ruminal inoculum.

PubMed

Hall, Mary Beth; Hatfield, Ronald D

2015-11-01

Microbial glycogen measurement is used to account for fates of carbohydrate substrates. It is commonly applied to washed cells or pure cultures which can be accurately subsampled, allowing the use of smaller sample sizes. However, the nonhomogeneous fermentation pellets produced with strained rumen inoculum cannot be accurately subsampled, requiring analysis of the entire pellet. In this study, two microbial glycogen methods were compared for analysis of such fermentation pellets: boiling samples for 3h in 30% KOH (KOH) or for 15min in 0.2M NaOH (NaOH), followed by enzymatic hydrolysis with α-amylase and amyloglucosidase, and detection of released glucose. Total α-glucan was calculated as glucose×0.9. KOH and NaOH did not differ in the α-glucan detected in fermentation pellets (29.9 and 29.6mg, respectively; P=0.61). Recovery of different control α-glucans was also tested using KOH, NaOH, and a method employing 45min of bead beating (BB). For purified beef liver glycogen (water-soluble) recovery, BB (95.0%)>KOH (91.4%)>NaOH (87.4%; P<0.05), and for wheat starch (water-insoluble granules) recovery, NaOH (96.9%)>BB (93.8%)>KOH (91.0%; P<0.05). Recovery of isolated protozoal glycogen (water-insoluble granules) did not differ among KOH (87.0%), NaOH (87.6%), and BB (86.0%; P=0.81), but recoveries for all were below 90%. Differences among substrates in the need for gelatinization and susceptibility to destruction by alkali likely affected the results. In conclusion, KOH and NaOH glycogen methods provided comparable determinations of fermentation pellet α-glucan. The tests on purified α-glucans indicated that assessment of recovery in glycogen methods can differ by the control α-glucan selected. Published by Elsevier B.V.

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.

Foamed Bulk Metallic Glass (Foam) Investigation

NASA Technical Reports Server (NTRS)

2004-01-01

This soldering iron has an evacuated copper capsule at the tip that contains a pellet of Bulk Metallic Glass (BMG) aboard the International Space Station (ISS). Prior to flight, researchers sealed a pellet of bulk metallic glass mixed with microscopic gas-generating particles into the copper ampoule under vacuum. Once heated in space, such as in this photograph, the particles generated gas and the BMG becomes a viscous liquid. The released gas made the sample foam within the capsule where each microscopic particle formed a gas-filled pore within the foam. The inset image shows the oxidation of the sample after several minutes of applying heat. Although hidden within the brass sleeve, the sample retained the foam shape when cooled, because the viscosity increased during cooling until it was solid.

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

PubMed

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

2007-05-01

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

Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

NASA Astrophysics Data System (ADS)

Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

2017-09-01

Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.

PubMed

Kaunisto, Erik; Marucci, Mariagrazia; Borgquist, Per; Axelsson, Anders

2011-10-10

The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Simulating Pelletization Strategies to Reduce the Biomass Supply Risk at America’s Biorefineries

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

Jacob J. Jacobson; Shane Carnohan; Andrew Ford

2014-07-01

Demand for cellulosic ethanol and other advanced biofuels has been on the rise, due in part to federal targets enacted in 2005 and extended in 2007. The industry faces major challenges in meeting these worthwhile and ambitious targets. The challenges are especially severe in the logistics of timely feedstock delivery to biorefineries. Logistical difficulties arise from seasonal production that forces the biomass to be stored in uncontrolled field-side environments. In this storage format physical difficulties arise; transportation is hindered by the low bulk density of baled biomass and the unprotected material can decay leading to unpredictable losses. Additionally, uncertain yieldsmore » and contractual difficulties can exacerbate these challenges making biorefineries a high-risk venture. Investors’ risk could limit business entry and prevent America from reaching the targets. This paper explores pelletizer strategies to convert the lignocellulosic biomass into a denser form more suitable for storage. The densification of biomass would reduce supply risks, and the new system would outperform conventional biorefinery supply systems. Pelletizer strategies exhibit somewhat higher costs, but the reduction in risk is well worth the extra cost if America is to grow the advanced biofuels industry in a sustainable manner.« less

Short-term bioassay responses to sludge products and leachate.

PubMed

Fjällborg, B; Gustafsson, N

2006-10-01

Recycling of sewage sludge is needed in a sustainable society. Quality aspects of sludge include hygiene (pathogens), nutrients (N and P), and toxicants (metals and organics). Metals are of particular concern because they are not degradable, but their hazards are related to their bioavailability and chemical speciation. In this article, the effect on sludge quality of two treatment methods, incineration and pelletization, has been determined for digested sludge from two treatment plants. The combined effect of nutrients and toxicants in sludge and sludge product was determined for spring wheat, Triticum aestivum, and the toxicity of the leachate water was determined for water fleas, Daphnia magna, and seeds of lettuce, Lactuca sativa. Toxicity Identification Evaluation was used to determine whether metals were possible toxicants. The results indicated that incineration decreased toxicity, whereas leachability of metals and the fertilizing effect was unaffected. Pelletization seemed to increase toxicity and leachability of metals and also decreased the fertilizing effect of the sludge. Thus, the results suggest that pelletization of digested sewage sludge increased the toxicity of the sludge and thus decreased the quality of the sludge, whereas incineration apparently reduced toxicity for the two sludges tested.

Converting campus waste into renewable energy - a case study for the University of Cincinnati.

PubMed

Tu, Qingshi; Zhu, Chao; McAvoy, Drew C

2015-05-01

This paper evaluates the implementation of three waste-to-energy projects at the University of Cincinnati: waste cooking oil-to-biodiesel, waste paper-to-fuel pellets and food waste-to-biogas, respectively. The implementation of these waste-to-energy (WTE) projects would lead to the improvement of campus sustainability by minimizing waste management efforts and reducing GHG emissions via the displacement of fossil fuel usage. Technical and economic aspects of their implementation were assessed and the corresponding GHG reduction was estimated. Results showed that on-site implementation of these projects would: (1) divert 3682L (974 gallons) of waste cooking oil to 3712L (982 gallons) of biodiesel; (2) produce 138tonnes of fuel pellets from 133tonnes of waste paper (with the addition of 20.75tonnes of plastics) to replace121tonnes of coal; and (3) produce biogas that would be enough to replace 12,767m(3) natural gas every year from 146tonnes of food waste. The economic analysis determined that the payback periods for the three projects would be 16months for the biodiesel, 155months for the fuel pellet, and 74months for the biogas projects. The reduction of GHG emission from the implementation of the three WTE projects was determined to be 9.37 (biodiesel), 260.49 (fuel pellets), and 11.36 (biogas) tonnes of CO2-eq per year, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transient ischemia reduces norepinephrine release during sustained ischemia. Neural preconditioning in isolated rat heart.

PubMed

Seyfarth, M; Richardt, G; Mizsnyak, A; Kurz, T; Schömig, A

1996-04-01

Endogenous catecholamine release may play a role in ischemic preconditioning either as a trigger or as a target within the process of myocardial preconditioning. Therefore, we investigated the effect of transient ischemia (TI) on norepinephrine release during sustained ischemia in isolated rat hearts. TI was induced by multiple cycles of global ischemia followed by reperfusion with a duration of 5 minutes each, comparable to ischemic preconditioning protocols. After TI, norepinephrine release was evoked by either sustained global ischemia, anoxia, cyanide intoxication, tyramine, or electrical stimulation. During TI, no washout of norepinephrine was observed, and tissue concentrations of norepinephrine were not changed. TI, however, reduced norepinephrine overflow after 20 minutes of sustained ischemia from 239 +/- 26 pmol/g (control) to 79+/-8 pmol/g (67% reduction, P <.01 ). A similar reduction of ischemia-induced norepinephrine release from 192 +/- 22 pmol/g (control) to 90 +/- 15 pmol/g was observed when hearts underwent transient anoxia without glucose (P < .05). When reperfusion between TI and sustained ischemia was prolonged from 5 to 90 minutes, the inhibitory effect of TI on norepinephrine release was gradually lost. Susceptibility to TI was a unique feature of norepinephrine release induced by sustained ischemia, since release of norepinephrine evoked by anoxia, cyanide intoxication, tyramine, or electrical stimulation remained unaffected by TI. We propose a protective effect of TI on neural tissue, which may reduce norepinephrine-induced damage during prolonged myocardial ischemia.

Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

PubMed

Kong, Hua; Yu, Fanglin; Liu, Yan; Yang, Yang; Li, Mingyuan; Cheng, Xiaohui; Hu, Xiaoqin; Tang, Xuemei; Li, Zhiping; Mei, Xingguo

2018-01-01

Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release. The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology. The expandable monolithic osmotic pump tablets containing nimodipine combined with poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic agent in semipermeable film were optimized. The release behavior was investigated both in vitro and in beagle dogs. It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained and complete release of nimodipine was also realized in beagles because the mean residence time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic pump tablets and the sustained release tablets in market. It was reasonable to believe that the sustained and complete release of poorly watersoluble nimodipine could be realized by using simple expandable monolithic osmotic pump technology combined with surfactant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Data summary of municipal solid waste management alternatives. Volume 4, Appendix B: RDF technologies

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

None

1992-10-01

This appendix contains background information, technical descriptions, economic data, mass and energy balances, and information on environmental releases for the refuse derived fuels (RDF) option in municipal solid waste management alternatives. Demonstration programs at St. Louis, Missouri; Franklin, Ohio; and Delaware are discussed. Information on pellet production and cofiring with coal is also presented.

Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

PubMed

Eggenreich, K; Windhab, S; Schrank, S; Treffer, D; Juster, H; Steinbichler, G; Laske, S; Koscher, G; Roblegg, E; Khinast, J G

2016-05-30

The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot. Copyright © 2016 Elsevier B.V. All rights reserved.

Eccentric contractions disrupt FKBP12 content in mouse skeletal muscle

PubMed Central

Baumann, Cory W.; Rogers, Russell G.; Gahlot, Nidhi; Ingalls, Christopher P.

2014-01-01

Abstract Strength deficits associated with eccentric contraction‐induced muscle injury stem, in part, from impaired voltage‐gated sarcoplasmic reticulum (SR) Ca2+ release. FKBP12 is a 12‐kD immunophilin known to bind to the SR Ca2+ release channel (ryanodine receptor, RyR1) and plays an important role in excitation‐contraction coupling. To assess the effects of eccentric contractions on FKBP12 content, we measured anterior crural muscle (tibialis anterior [TA], extensor digitorum longus [EDL], extensor hallucis longus muscles) strength and FKBP12 content in pellet and supernatant fractions after centrifugation via immunoblotting from mice before and after a single bout of either 150 eccentric or concentric contractions. There were no changes in peak isometric torque or FKBP12 content in TA muscles after concentric contractions. However, FKBP12 content was reduced in the pelleted fraction immediately after eccentric contractions, and increased in the soluble protein fraction 3 day after injury induction. FKBP12 content was correlated (P = 0.025; R2= 0.38) to strength deficits immediately after injury induction. In summary, eccentric contraction‐induced muscle injury is associated with significant alterations in FKBP12 content after injury, and is correlated with changes in peak isometric torque. PMID:25347864

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

PubMed Central

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

2013-01-01

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

An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

PubMed

Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

2014-04-01

It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

Axisymmetric whole pin life modelling of advanced gas-cooled reactor nuclear fuel

NASA Astrophysics Data System (ADS)

Mella, R.; Wenman, M. R.

2013-06-01

Thermo-mechanical contributions to pellet-clad interaction (PCI) in advanced gas-cooled reactors (AGRs) are modelled in the ABAQUS finite element (FE) code. User supplied sub-routines permit the modelling of the non-linear behaviour of AGR fuel through life. Through utilisation of ABAQUS's well-developed pre- and post-processing ability, the behaviour of the axially constrained steel clad fuel was modelled. The 2D axisymmetric model includes thermo-mechanical behaviour of the fuel with time and condition dependent material properties. Pellet cladding gap dynamics and thermal behaviour are also modelled. The model treats heat up as a fully coupled temperature-displacement study. Dwell time and direct power cycling was applied to model the impact of online refuelling, a key feature of the AGR. The model includes the visco-plastic behaviour of the fuel under the stress and irradiation conditions within an AGR core and a non-linear heat transfer model. A multiscale fission gas release model is applied to compute pin pressure; this model is coupled to the PCI gap model through an explicit fission gas inventory code. Whole pin, whole life, models are able to show the impact of the fuel on all segments of cladding including weld end caps and cladding pellet locking mechanisms (unique to AGR fuel). The development of this model in a commercial FE package shows that the development of a potentially verified and future-proof fuel performance code can be created and used. The usability of a FE based fuel performance code would be an enhancement over past codes. Pre- and post-processors have lowered the entry barrier for the development of a fuel performance model to permit the ability to model complicated systems. Typical runtimes for a 5 year axisymmetric model takes less than one hour on a single core workstation. The current model has implemented: Non-linear fuel thermal behaviour, including a complex description of heat flow in the fuel. Coupled with a variety of different FE and finite difference models. Non-linear mechanical behaviour of the fuel and cladding including, fuel creep and swelling and cladding creep and plasticity each with dependencies on a variety of different properties. A fission gas release model which takes inputs from first principles calculations. Explicitly integrated inventory calculations performed in a coupled manner. Freedom to model steady state and transient behaviour using implicit time integration. The whole pin geometry is considered over an entire typical fuel life. The model showed by examination of normal operation and a subsequent transient chosen for software demonstration purposes: ABAQUS may be a sufficiently flexible platform to develop a complete and verified fuel performance code. The importance and effectiveness of the geometry of the fuel spacer pellets was characterised. The fuels performance under normal conditions (high friction no power spikes) would not suggest serious degradation of the cladding in fuel life. Large plastic strains were found when pellet bonding was strong, these would appear at all pellets cladding triple points and all pellet radial crack and cladding interfaces thus showing a possible axial direction to cracks forming from ductility exhaustion.

Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency.

PubMed

McMahon, Chris G; Shusterman, Neil; Cohen, Brian

2017-07-01

Implantation of testosterone doses of at least 150 to 450 mg (ie, two to six pellets) is common clinical practice despite a lack of prospective data. To evaluate pharmacokinetics, clinical efficacy, safety, and patient-reported outcomes in men with androgen deficiency who received implantation of testosterone pellets (900 mg) in an open-label study. Men with androgen deficiency (serum testosterone < 300 ng/dL [10.4 nmol/L]) were screened and received 12 testosterone pellets (900 mg). Serum hormone measurements (total and free testosterone, dihydrotestosterone, and estradiol) were obtained on days 1, 5, 8, 15, 29, 57, 85, and 113. All hormones were assayed using validated liquid chromatography and tandem mass spectrometry. Pharmacokinetics of selected hormones was determined. The patient-reported International Index of Erectile Function (IIEF), Center for Epidemiologic Studies Depression (CES-D), and Androgen Deficiency in the Aging Male (qADAM) questionnaires also were performed. Patients rated their satisfaction on a scale from 1 (very satisfied) to 5 (very dissatisfied). Adverse events were monitored throughout. Fifteen patients were included (mean age = 54.5 years, SD = 8.6 years). Mean baseline total testosterone concentration was 241.6 ng/dL (SD = 88.8 ng/dL; mean = 8.4 nmol/L, SD = 3.1 nmol/L). Mean testosterone serum concentrations fluctuated during the first 2 weeks (range = 300-1,000 ng/dL, 10.4-34.7 nmol/L) but remained higher than or equal to 300 ng/dL (10.4 nmol/L) through day 113. Concentrations of free testosterone, dihydrotestosterone, and estradiol mirrored that of total testosterone. Male functioning (IIEF score), depression (CES-D total score), and androgen-deficiency symptoms (qADAM total score) improved from baseline. Most patients were "very satisfied" (40.0%) or "quite satisfied" (26.7%) with treatment. Testosterone pellets were well tolerated. Pellet extrusion and polycythemia occurred in one patient each. Implantation of high doses (900 mg) of testosterone pellets are generally well tolerated and could provide clinical benefit for some patients. This study provides standardized data for the implantation of 12 testosterone pellets. However, the open-label uncontrolled design of this study and its small and ethnically non-diverse patient population limit the interpretation of these data, particularly the patient-reported outcomes. Implantation of 12 testosterone pellets (900 mg) was well tolerated and provided adequate and sustained serum testosterone concentrations. Additional randomized controlled trials are needed to confirm efficacy and safety findings. McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med 2017;14:883-890. Copyright © 2017. Published by Elsevier Inc.

Long-term biobarriers to plant and animal intrusions of uranium tailings. [24% trifluralin, 18% carbon black, and 58% polymer

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

Cline, J.F.; Burton, F.G.; Cataldo, D.A.

1982-09-01

The objective of this project was to develop and evaluate the effectiveness of physical and chemical barriers designed to prevent plant and animal breachment of uranium mill tailings containment systems for an extended period of time. A polymeric carrier/biocide delivery system was developed and tested in the laboratory, greenhouse and field. A continuous flow technique was established to determine the release rates of the biocides from the PCD systems; polymeric carrier specifications were established. Studies were conducted to determine effective biocide concentrations required to produce a phytotoxic response and the relative rates of phytotoxin degradation resulting from chemical and biologicalmore » breakdown in soils. The final PCD system developed was a pelletized system containing 24% trifluralin, 18% carbon black and 58% polymer. Pellets were placed in the soil at the Grand Junction U-tailings site at one in. and two in. intervals. Data obtained in the field determined that the pellets released enough herbicide to the soil layer to stop root elongation past the barrier. Physical barriers to subsurface movement of burrowing animals were investigated. Small crushed stone (1 to 1 1/2 in. diameter) placed over asphalt emulsion and multilayer soil seals proved effective as barriers to a small mammal (ground squirrels) but were not of sufficient size to stop a larger animal (the prairie dog). No penetrations were made through the asphalt emulsion or the clay layer of the multilayer soil seals by either of the two mammals tested. A literature survey was prepared and published on the burrowing habits of the animals that may be found at U-tailings sites.« less

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

NASA Astrophysics Data System (ADS)

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

2007-06-01

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

Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

PubMed

Tanetsugu, Yusuke; Tagami, Tatsuaki; Terukina, Takayuki; Ogawa, Takaya; Ohta, Masato; Ozeki, Tetsuya

2017-01-01

Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

Management of asymptomatic intracardiac missiles using echocardiography.

PubMed

Robison, R J; Brown, J W; Caldwell, R; Stone, K S; King, H

1988-09-01

A child sustained a low-velocity airgun pellet injury to the left ventricle. No cardiovascular compromise was produced. The foreign body was localized by two-dimensional echocardiography to the left ventricular chamber near the mitral valve, and subsequently removed through a left atriotomy incision. In asymptomatic patients, missiles clearly embedded within a chamber wall may be observed; all others should be removed. Two-dimensional echocardiography is recommended for localization.

Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

PubMed

Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

2012-01-01

Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

Optimization of chitosan nanoparticles for colon tumors using experimental design methodology.

PubMed

Jain, Anekant; Jain, Sanjay K

2016-12-01

Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.

In-vitro trials to ascertain sustained release efficacy of assembly pheromone micro particles for the control of brown dog tick, Rhipicephalus sanguineus.

PubMed

Bhoopathy, Dhivya; Bhaskaran Ravi, Latha

2017-12-01

Sustained release micro particles were prepared incorporating assembly pheromone and deltamethrin. Two natural polymers, namely, chitosan and calcium alginate and a synthetic polymer, poly-ε-caprolactone were used for encapsulating the assembly pheromone-acaricide combination. The micro particles were subjected to in vitro evaluation freshly after preparation and then at monthly intervals to assess their sustained release efficacy. The response of the unfed stages of dog tick, Rhipicephalus sanguineus to fresh and aged micro particles was assessed and results were recorded. The micro particles were found to release assembly pheromone in a sustained manner up to 2 months of study period.

Growth performance, diet nutrient digestibility, and bone mineralization in weaned pigs fed pelleted diets containing thermostable phytase.

PubMed

Yáñez, J L; Landero, J L; Owusu-Asiedu, A; Cervantes, M; Zijlstra, R T

2013-02-01

Traditional supplemental dietary phytase loses activity during steam pelleting. The thermal tolerance and bioefficacy of a phytase product with a thermoprotective coating [coated phytase (C-phytase)] was compared in mash and pelleted diets to a traditional, uncoated phytase (U-phytase) added to a negative control (NC) diet, formulated with reduced dietary Ca and P, and compared with a corn-soybean meal based positive control (POC) diet. Growth performance, nutrient digestibility, and third metacarpal bone characteristics were response variables. Weaned pigs (n = 56; 8.20 ± 0.5 kg initial BW; 28 d of age) were individually housed and randomly allotted to 1 of 7 diets for 21 d. The diets were 1) POC mash, 2) NC mash, 3) NC pelleted at 90°C, 4) NC mash + 500 U/kg U-phytase, 5) NC mash + 500 U/kg C-phytase, 6) NC + 500 U/kg C-phytase pelleted at 80°C, and 7) NC + 500 U/kg C-phytase pelleted at 90°C. The POC and NC diets were formulated to be isoenergetic and isolysinic. The content of Ca and available P was 1.01 and 0.40% and 0.83 and 0.22% in the POC and NC diets, respectively. Pig BW and feed intake were measured on d 7, 14, and 21, and feces were collected for 2 d. On d 21, pigs were killed and ileal digesta and the third metacarpal bone collected. Pigs fed POC had greater (P < 0.05) ADG, G:F, P digestibility, and bone mineralization but lower (P < 0.01) energy digestibility than pigs fed NC. Pelleting the NC diet did not improve performance, nutrient digestibility, or P use. Adding the U-phytase to NC mash diet increased (P < 0.05) ADG, G:F, apparent ileal digestibility (AID) of CP and Ile, Leu, Phe, Thr, Val, and Ser, and apparent total tract digestibility (ATTD) of P compared with pigs fed NC. Pigs fed C-phytase in NC mash diets had increased (P < 0.05) G:F and an AID of CP and AA and ATTD of P compared with pigs fed NC but not different than pigs fed U-phytase NC mash diets. Pigs fed pelleted NC diet with C-phytase had a greater (P < 0.05) ATTD of P and energy than pigs fed mash NC diet with C-phytase but had similar growth performance, AID of CP and AA, and bone mineralization to pigs fed U-phytase. In conclusion, release and bioefficacy of phytase after pelleting was not affected by the thermal protective coating.

Effect of Quaternary Ammonium Carboxymethylchitosan on Release Rate In-vitro of Aspirin Sustained-release Matrix Tablets

PubMed Central

Meng, Lingbin; Teng, Zhongqiu; Zheng, Nannan; Meng, Weiwei; Dai, Rongji; Deng, Yulin

2013-01-01

The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets. PMID:24250627

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

A Preliminary Trial: Double-Blind Comparison of Nefazodone, Bupropion-SR and Placebo in the Treatment of Cannabis Dependence

PubMed Central

Carpenter, Kenneth M.; McDowell, David; Brooks, Daniel J.; Cheng, Wendy; Levin, Frances R.

2009-01-01

The present study investigated the efficacy of nefazodone and bupropion-sustained release for treating cannabis dependence. A double blind, placebo controlled, piggy back design was employed to assess if nefazodone and bupropion-sustained release increased the probability of abstinence from cannabis and reduced the severity of cannabis dependence and cannabis withdrawal symptoms during a 13-week outpatient treatment program. One-hundred and six participants (M=32 years; Females n=25) were randomized to one of three medication conditions (nefazodone, bupropion-sustained release, or placebo) and participated in a weekly individually based coping skills therapy program. Results indicated a an increased probability of achieving abstinence over the course of treatment and a decrease in the severity of cannabis dependence and the withdrawal symptom of irritability. There were no significant effects demonstrated for nefazodone and bupropion-sustained release on cannabis use or cannabis withdrawal symptoms. The results indicate nefazodone and bupropion-sustained release may have limited efficacy in treating cannabis dependence. PMID:19219666

The preparation by extrusion/spheronization and the properties of pellets containing drugs, microcrystalline cellulose and glyceryl monostearate.

PubMed

Chatchawalsaisin, Jittima; Podczeck, Fridrun; Newton, J Michael

2005-01-01

Pellets have been prepared by extrusion and spheronization containing microcrystalline cellulose (MCC) and four model drugs with decreasing order of solubility, paracetamol (P), diclofenac sodium (D), ibuprofen (IB) and indomethacin (IN) at a 10% level with and without the addition of a range of levels of glyceryl monostearate (GMS). The drugs differed in their response to extrusion in that all formulations containing the drug D had a 'steady state' extrusion profile whereas the other three drugs exhibited 'forced flow' indicating the possibility of water migration during the process of ram extrusion. The presence of GMS did not influence this effect. The drug D also required consistently less water to function than the other three drugs. In spite of these differences in extrusion performance, it was possible to prepare satisfactory pellets from formulations of all the drugs with 0, 30 and 60% GMS combined with 90, 60 or 30% of MCC at a range of water levels. It was also possible to prepare pellets containing the drug D with 70, 80 and 90% GMS, with corresponding quantities of 20, 10 and 0% of MCC. It was also possible to prepare the pellet formulations by dispersing the drugs in molten GMS, grinding and processing this with MCC and water. Such systems retained the processing characteristics of the composition made by the blending of the powder. The presence of GMS in all cases reduced the quantity of water required for the process to function. The steady state or the mean of the range of the forces observed during forced flow, were dependent on the composition and the quantity of water added. The surface of the extrudate appeared smooth and measurements of surface roughness established that the value of the rugosity R(a) for any of the extrudates did not exceed 6 microm. The extrudate diameter was found to increase with the quantity of GMS in the formulation. The pellets produced were all within a relatively narrow size range (three sieve fractions of a root two progression), the median value of which increased with the level of GMS. For the drug D, there was a linear increase of pellet diameter with increase in the extrudate diameter. For the three other drugs this relationship was less certain but nevertheless there was a similar trend for the pellet diameter to increase as the extrudate diameter increased, suggesting the mechanism of the process is the same irrespective of the composition. Considering the value of the shape factor e(R), all the pellets produced from the various formulations were well within acceptable levels for further processing and the only observable trend in the values was that the formulations with the lower water contents were the least round. The porosity of the pellets of the different formulations generally decreased with the increase in water used to prepare the pellets, the extent of this decrease being dependent on the drug and the level of GMS. The in vitro drug release from the pellets was controlled by the solubility of the drug, the lower the value of the solubility, the longer the mean dissolution time (MDT). This was not influenced by the presence of GMS or the method of incorporation of the drug into the formulation.

[Preparation of curcumin-EC sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Bai, Wei-li; Yan, Ting-yuan; Wang, Zhi-xiang; Huang, De-chun; Yan, Ting-xuan; Li, Ping

2015-01-01

Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Development of Intra-knee Joint Sustained-Release Gel Formulation and Evaluation of Its Pharmacological Efficiency in Rats.

PubMed

Noda, Takehiro; Okuda, Tomoyuki; Ban, Kousuke; Mizuno, Ryota; Tagami, Tatsuaki; Ozeki, Tetsuya; Okamoto, Hirokazu

2017-06-01

In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.

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

Tu, Qingshi; Zhu, Chao; McAvoy, Drew C., E-mail: mcavoydm@ucmail.uc.edu

Highlights: • A case study to show the benefits of waste-to-energy projects at a university. • Evaluated the technical and economic feasibilities as well as GHG reduction. • A tool for other universities/communities to evaluate waste-to-energy projects. - Abstract: This paper evaluates the implementation of three waste-to-energy projects at the University of Cincinnati: waste cooking oil-to-biodiesel, waste paper-to-fuel pellets and food waste-to-biogas, respectively. The implementation of these waste-to-energy (WTE) projects would lead to the improvement of campus sustainability by minimizing waste management efforts and reducing GHG emissions via the displacement of fossil fuel usage. Technical and economic aspects of theirmore » implementation were assessed and the corresponding GHG reduction was estimated. Results showed that on-site implementation of these projects would: (1) divert 3682 L (974 gallons) of waste cooking oil to 3712 L (982 gallons) of biodiesel; (2) produce 138 tonnes of fuel pellets from 133 tonnes of waste paper (with the addition of 20.75 tonnes of plastics) to replace121 tonnes of coal; and (3) produce biogas that would be enough to replace 12,767 m{sup 3} natural gas every year from 146 tonnes of food waste. The economic analysis determined that the payback periods for the three projects would be 16 months for the biodiesel, 155 months for the fuel pellet, and 74 months for the biogas projects. The reduction of GHG emission from the implementation of the three WTE projects was determined to be 9.37 (biodiesel), 260.49 (fuel pellets), and 11.36 (biogas) tonnes of CO{sub 2}-eq per year, respectively.« less

Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

PubMed

Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

2015-01-01

Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release.

PubMed

Thote, Amol J; Gupta, Ram B

2005-03-01

Our purpose was to produce nanoparticles of a hydrophilic drug with use of supercritical carbon dioxide (CO2), encapsulate the obtained nanoparticles into polymer microparticles with use of an anhydrous method and study their sustained in vitro drug release. The hydrophilic drug, dexamethasone phosphate, is dissolved in methanol and injected in supercritical CO2 with an ultrasonic field for enhanced molecular mixing (supercritical antisolvent technique with enhanced mass transfer [SAS-EM]). Supercritical CO2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles. The nanoparticles are then encapsulated in poly(lactide-co-glycolide) (PLGA) polymer by use of the anhydrous solid-oil-oil-oil technique. This results in a well-dispersed encapsulation of drug nanoparticles in polymer microspheres. In vitro drug release from these microparticles is studied. With supercritical CO2 used as an antisolvent, nanoparticles of dexamethasone phosphate were obtained in the range of 150 to 200 nm. On encapsulation in polylactide coglycolide, composite microspheres of approximately 70 microm were obtained. The in vitro drug release of these nanoparticles/microparticles composites shows sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release. Nanoparticles of dexamethasone phosphate can be produced with the SAS-EM technique. When microencapsulated, these particles can provide sustained drug release without initial burst release. Because the complete process is anhydrous, it can be easily extended to produce sustained release formulations of other hydrophilic drugs.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

PubMed

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Towards Integrated Multi-Trophic Aquaculture: Lessons from Caprellids (Crustacea: Amphipoda)

PubMed Central

Hachero-Cruzado, Ismael; González-Romero, Pablo; Jiménez-Prada, Pablo; Cassell, Christopher; Ros, Macarena

2016-01-01

The search for alternative live feed organisms and the progression of Integrative Multi-Trophic Aquaculture (IMTA) are currently being highly prioritised in EU strategies. Caprellids could potentially be an important exploitable resource in aquaculture due to their high levels of beneficial polyunsaturated fatty acids, fast growing nature and widespread distribution. Furthermore, since they are mainly detritivorous, they could be excellent candidates for integration into IMTA systems, potentially benefitting from uneaten feed pellets and faeces released by cultured fish in fish farms and sea-cage structures. Despite this, there is a lack of experimental studies to: (i) test inexpensive diets for caprellids, such as detritus, (ii) develop sustainable caprellid culture techniques and (iii) include caprellids in IMTA systems. The main aim of this study was to determine whether detritus (D) in the form of fish faeces provided an adequate diet for caprellids in comparison to other traditional diets, such as Artemia nauplii (A) or phytoplankton (P). Adult survival rate was shown to be significantly higher for caprellids fed with D. Conversely, hatchlings had the highest survival rate with A, although the juvenile growth rate and number of moults was similar in the three diets. With regard to lipid composition, caprellids fed with A had higher concentrations of Triacylglycerols (TAG) and Phosphatidylcholine (PC) while those fed with P or D were richer in polyunsaturated fatty acids, especially 22:6(n-3) (DHA). Interestingly, caprellids fed with D were also a rich source of 18:2(n-6) (LA), considered to be an essential fatty acid in vertebrates. It was found that detritus based mainly on fish faeces and uneaten feed pellets can be considered an adequate feed for adult caprellids, providing a source of both omega-3 (DHA) and omega-6 (LA) fatty acids. Hatchlings however seem to require an additional input of TAG and PC during juvenile stages to properly grow. PMID:27124465

Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

PubMed

Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

2015-01-01

This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

Development of a real-time simulation tool towards self-consistent scenario of plasma start-up and sustainment on helical fusion reactor FFHR-d1

NASA Astrophysics Data System (ADS)

Goto, T.; Miyazawa, J.; Sakamoto, R.; Suzuki, Y.; Suzuki, C.; Seki, R.; Satake, S.; Huang, B.; Nunami, M.; Yokoyama, M.; Sagara, A.; the FFHR Design Group

2017-06-01

This study closely investigates the plasma operation scenario for the LHD-type helical reactor FFHR-d1 in view of MHD equilibrium/stability, neoclassical transport, alpha energy loss and impurity effect. In 1D calculation code that reproduces the typical pellet discharges in LHD experiments, we identify a self-consistent solution of the plasma operation scenario which achieves steady-state sustainment of the burning plasma with a fusion gain of Q ~ 10 was found within the operation regime that has been already confirmed in LHD experiment. The developed calculation tool enables systematic analysis of the operation regime in real time.

Sensor array for the detection of organic and inorganic contaminants in post-consumer recycled plastics for food contact.

PubMed

Davis, Nathan; Danes, Jeffrey E; Vorst, Keith

2017-10-01

Post-consumer recycled (PCR) plastic material is made by collecting used plastic products (e.g., bottles and other plastic packaging materials) and reprocessing them into solid-state pellets or flakes. Plastic recycling has positive environmental benefits, but may also carry potential drawbacks due to unwanted organic and inorganic contaminants. These contaminants can migrate into food packaging made from these recycled plastic materials. The purpose of this research was to identify economically viable real-time monitoring technologies that can be used during the conversion of virgin and recycled resin feedstocks (i.e., various blends of virgin pellets and recycled solid-state pellet or mechanically ground flake) to final articles to ensure the safety, quality and sustainability of packaging feedstocks. Baseline analysis (validation) of real-time technologies was conducted using industry-standard practices for polymer analysis. The data yielded supervised predictive models developed by training sessions completed in a controlled laboratory setting. This technology can be employed to evaluate compliance and aid converters in commodity sourcing of resin without exceeding regulatory thresholds. Furthermore, this technology allowed for real-time decision and diversion strategies during the conversion of resin and flake to final articles or products to minimise the negative impact on human health and environmental exposure.

The preparation and the sustained release of titanium dioxide hollow particles encapsulating L-ascorbic acid

NASA Astrophysics Data System (ADS)

Tominaga, Yoko; Kadota, Kazunori; Shimosaka, Atsuko; Yoshida, Mikio; Oshima, Kotaro; Shirakawa, Yoshiyuki

2018-05-01

The preparation of the titanium dioxide hollow particles encapsulating L-ascorbic acid via sol-gel process using inkjet nozzle has been performed, and the sustained release and the effect protecting against degradation of L-ascorbic acid in the particles were investigated. The morphology of titanium dioxide particles was evaluated by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The sustained release and the effect protecting against degradation of L-ascorbic acid were estimated by dialysis bag method in phosphate buffer saline (PBS) (pH = 7.4) as release media. The prepared titanium dioxide particles exhibited spherical porous structures. The particle size distribution of the titanium dioxide particles was uniform. The hollow titanium dioxide particles encapsulating L-ascorbic acid showed the sustained release. It was also found that the degradation of L-ascorbic acid could be inhibited by encapsulating L-ascorbic acid in the titanium dioxide hollow particles.

Magnetic modulation of release of macromolecules from polymers.

PubMed Central

Hsieh, D S; Langer, R; Folkman, J

1981-01-01

Sustained-release systems were made by incorporating bovine serum albumin and magnetic steel beads in an ethylene-vinyl acetate copolymer matrix. When exposed to aqueous medium, the polymer matrix released the albumin slowly and continuously. Application of an oscillating magnetic field increased the release rate by as much as 100%. Intervals of 6-hr periods of magnetic exposure and nonexposure were alternated over a 5-day period, resulting in corresponding increases and decreases in release and establishing a pattern of modulated sustained release. Images PMID:6940193

Oral sustained-release suspension based on a lauryl sulfate salt/complex.

PubMed

Kasashima, Yuuki; Uchida, Shinya; Yoshihara, Keiichi; Yasuji, Takehiko; Sako, Kazuhiro; Namiki, Noriyuki

2016-12-30

The objective of this study was to evaluate the feasibility of lauryl sulfate (LS) salt/complex as a novel carrier in oral sustained-release suspensions. Mirabegron, which has a pH-dependent solubility, was selected as the model drug. Sodium lauryl sulfate (SLS) was bound to mirabegron in a stoichiometric manner to form an LS salt/complex. LS salt/complex formulation significantly reduced the solubility of mirabegron and helped mirabegron achieve sustained-release over a wide range of pH conditions. Microparticles containing the LS salt/complex were prepared by spray drying with the aqueous dispersion of ethylcellulose (Aquacoat ® ECD). The diameter of the microparticles was less than 200μm, which will help avoid a gritty taste. In vitro results indicated the microparticles had slower dissolution profiles than the LS salt/complex. The dissolution rate could be controlled flexibly by changing the amount of Aquacoat ® ECD. The microparticle suspension retained the desired sustained-release property and dissolution profile after being stored for 30days at 40°C. In addition, the suspension displayed sustained-release behavior in dogs without a pronounced C max peak, which will help prevent side effects. These results suggest that microparticles containing LS salt/complex may be useful as a novel sustained-release suspension for oral delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

21 CFR 520.2260b - Sulfamethazine sustained-release boluses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sulfamethazine sustained-release boluses. 520.2260b Section 520.2260b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... weight. (ii) Indications for use. Beef and nonlactating cattle for sustained treatment of shipping fever...

21 CFR 520.2260b - Sulfamethazine sustained-release boluses.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sulfamethazine sustained-release boluses. 520.2260b Section 520.2260b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... weight. (ii) Indications for use. Beef and nonlactating cattle for sustained treatment of shipping fever...

21 CFR 520.2260b - Sulfamethazine sustained-release boluses.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sulfamethazine sustained-release boluses. 520.2260b Section 520.2260b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... weight. (ii) Indications for use. Beef and nonlactating cattle for sustained treatment of shipping fever...

Dynamic response of laser ablative shock waves from coated and uncoated amorphous Boron nanoparticles

NASA Astrophysics Data System (ADS)

Paturi, Prem Kiran; Chelikani, Leela; Pinnoju, Venkateshwarlu; Verma, Pankaj; Singh, Raja V.; Acrhem Collaboration; Hemrl Collaboration

2015-06-01

Nanoparticles (NP) improve the performance of solid rocket motors with increased burning rate and lower ignition threshold owing to their larger surface area. We present spatio-temporal evolution of laser ablative shock waves (LASWs) from compacted amorphous Boron (B) and Lithium Fluoride coated Boron (LiF-B) of 70-110nm sizes that were compacted to form pellets. Thickness of the LiF coating is 5.5 +/- 1 nm in LiF-B. Laser pulses from second harmonic of Nd:YAG laser (532 nm, 7 ns) are used to generate LASWs expanding in ambient air. The precise time of energy release from the pellets under extreme ablative pressures is studied using shadowgraphy with a temporal resolution of 1.5 ns. Different nature of the shock front (SF) following Sedov-Taylor theory, before and after detachment, indicated two specific time dependent stages of energy release. From the position of SF, velocity behind the SF, similar to that of exhaust velocity is measured. Specific impulse of 241 +/- 5 and 201 +/- 4 sec for LiF-B and B, respectively, at a delay of 0.8 μs from shock inducing laser pulse makes them potential candidates for laser based micro thruster applications. The work is supported by Defence Research and Developement Organization, India through Grants-in-Aid Program.

[The possibilities for the expert assessment of the influence of the structural features of a hunting weapon barrel on the characteristics of injuries inflicted by the multi-element ammunition in a cylindrical container].

PubMed

Makarov, I Yu; Suvorov, A S; Lorents, A S

The objective of the present study was to analyze the available information contained in the special literature concerning the possibilities for the expert assessment of the influence of the constructive and ballistic characteristics of hunting weapon barrels («cylinder» versus «choke») and their regular ammunition (equipped with pellets placed in a special wad-container and without it) on the mechanisms of damage formation. It was shown that the barrel muzzle narrowing produces the well apparent effect on the process of formation and release of all the damaging factors of the shot which makes it difficult to diagnose the resultant damage. It is concluded that the use of shooting ammunition with the pellets enclosed in wad-containers creates the objective prerequisite for the differentiation between its different types.

Morphological evidence for phages in Xylella fastidiosa

PubMed Central

Chen, Jianchi; Civerolo, Edwin L

2008-01-01

Presumptive phage particles associated with Xylella fastidiosa strain Temecula-1 grown in PW broth were observed by transmission electron microscopy (TEM) in ultrathin sections of bacterial cell-containing low speed centrifugation pellets and in partially purified preparations from CsCl equilibrium centrifugation density gradients. Ultrathin-sectioned cell pellets contained icosahedral particles of about 45 nm in diameter. Samples collected from CsCl density gradients revealed mostly non-tailed icosahedral but also tailed particles. The icosahedral particles could be divided into two types: a large type (about 45 nm) and a small type (about 30 nm). Filamentous phage-like particles (17 × 120 to 6,300 nm) were also observed. The presence of different types of phage-like particles resembling to those in several bacteriophage families provides new physical evidence, in addition to X. fastidiosa genomic information, that X. fastidiosa possesses active phages. This is the first report of phage particles released in X. fastidiosa cultures. PMID:18538030

The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone.

PubMed

Laidlaw, I J; Clarke, R B; Howell, A; Owen, A W; Potten, C S; Anderson, E

1995-01-01

In order to resolve the question of which ovarian steroid stimulates normal human mammary epithelial cell proliferation, we have implanted pieces of normal human breast tissue subcutaneously into athymic nude mice. These mice were then treated with slow-release pellets containing estradiol (E2) or progesterone (P) such that serum levels of E2 and P were increased to those seen in normal women. The proliferative activity of the tissue implants was assessed by uptake of tritiated thymidine and steroid receptor expression was measured immunocytochemically. Insertion of a 2 mg E2 pellet 14 days after tissue implantation increased the thymidine labeling index (TLI) from a median of 0.4% (n = 34) to a median of 2.1% after 7 days (n = 43; P < 0.001 by Mann Whitney U test). In contrast, treatment with a P pellet (4 mg) had no effect upon the TLI whereas P (4 mg) in combination with E2 (2 mg) had no effect over and above that of E2 alone. There was a significant correlation between the increase in TLI and either the E2 content of the pellets (P < 0.001 by linear regression) or the serum E2 levels achieved (P < 0.001). Expression of the P receptor was increased 15- to 20-fold by E2 treatment. We conclude that E2 is sufficient to stimulate human breast epithelial cell proliferation at physiologically relevant concentrations and that P does not affect proliferation either alone or after E2 priming.

3D modeling of missing pellet surface defects in BWR fuel

DOE PAGES

Spencer, B. W.; Williamson, R. L.; Stafford, D. S.; ...

2016-07-26

One of the important roles of cladding in light water reactor fuel rods is to prevent the release of fission products. To that end, it is essential that the cladding maintain its integrity under a variety of thermal and mechanical loading conditions. Local geometric irregularities in fuel pellets caused by manufacturing defects known as missing pellet surfaces (MPS) can in some circumstances lead to elevated cladding stresses that are sufficiently high to cause cladding failure. Accurate modeling of these defects can help prevent these types of failures. The BISON nuclear fuel performance code developed at Idaho National Laboratory can bemore » used to simulate the global thermo-mechanical fuel rod behavior, as well as the local response of regions of interest, in either 2D or 3D. In either case, a full set of models to represent the thermal and mechanical properties of the fuel, cladding and plenum gas is employed. A procedure for coupling 2D full-length fuel rod models to detailed 3D models of the region of the rod containing a MPS defect is detailed in this paper. The global and local model each contain appropriate physics and behavior models for nuclear fuel. This procedure is demonstrated on a simulation of a boiling water reactor (BWR) fuel rod containing a pellet with an MPS defect, subjected to a variety of transient events, including a control blade withdrawal and a ramp to high power. The importance of modeling the local defect using a 3D model is highlighted by comparing 3D and 2D representations of the defective pellet region. Finally, parametric studies demonstrate the effects of the choice of gaseous swelling model and of the depth and geometry of the MPS defect on the response of the cladding adjacent to the defect.« less

Lyophilized Silk Fibroin Hydrogels for the Sustained Local Delivery of Therapeutic Monoclonal Antibodies

PubMed Central

Guziewicz, Nicholas; Best, Annie; Perez-Ramirez, Bernardo; Kaplan, David L.

2011-01-01

The development of sustained delivery systems compatible with protein therapeutics continues to be a significant unmet need. A lyophilized silk fibroin hydrogel matrix (lyogel) for the sustained release of pharmaceutically relevant monoclonal antibodies is described. Sonication of silk fibroin prior to antibody incorporation avoids exposing the antibody to the sol-gel transition inducing shear stress. Fourier Transform Infrared (FTIR) analysis showed no change in silk structural composition between hydrogel and lyogel or with increasing silk fibroin concentration. Antibody release from hydrogels occurred rapidly over 10 days regardless of silk concentration. Upon lyophilization, sustained antibody release was observed over 38 days from lyogels containing 6.2% (w/w) silk fibroin and above. In 3.2% (w/w) silk lyogels, antibody release was comparable to hydrogels. Swelling properties of lyogels followed a similar threshold behavior. Lyogels at 3.2% (w/w) silk recovered approximately 90% of their fluid mass upon rehydration, while approximately 50% fluid recovery was observed at 6.2% (w/w) silk and above. Antibody release was primarily governed by hydrophobic/hydrophilic silk-antibody interactions and secondarily altered by the hydration resistance of the lyogel. Hydration resistance was controlled by altering β-sheet (crystalline) density of the matrix. The antibody released from lyogels maintained biological activity. Silk lyogels offer an advantage as a delivery matrix over other hydrogel materials for the slow release of the loaded protein, making lyogels suitable for long-term sustained release applications. PMID:21216004

Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

NASA Astrophysics Data System (ADS)

Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

2014-02-01

Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

Fission product release and microstructure changes of irradiated MOX fuel at high temperatures

NASA Astrophysics Data System (ADS)

Colle, J.-Y.; Hiernaut, J.-P.; Wiss, T.; Beneš, O.; Thiele, H.; Papaioannou, D.; Rondinella, V. V.; Sasahara, A.; Sonoda, T.; Konings, R. J. M.

2013-11-01

Samples of irradiated MOX fuel of 44.5 GWd/tHM mean burn-up were prepared by core drilling at three different radial positions of a fuel pellet. They were subsequently heated in a Knudsen effusion mass spectrometer up to complete vaporisation of the sample (˜2600 K) and the release of fission gas (krypton and xenon) as well as helium was measured. Scanning electron microscopy was used in parallel to investigate the evolution of the microstructure of a sample heated under the same condition up to given key temperatures as determined from the gas release profiles. A clear initial difference for fission gas release and microstructure was observed as a function of the radial position of the samples and therefore of irradiation temperature. A good correlation between the microstructure evolution and the gas release peaks could be established as a function of the temperature of irradiation and (laboratory) heating. The region closest to the cladding (0.58 < r/r0 < 0.96), designated as sample type A in Fig. 1. It represents the "cooler" part of the fuel pellet. The irradiation temperatures (Tirrad) in this range are from 854 to 1312 K (ΔT: 458 K). The intermediate radial zone of the pellet (0.42 < r/r0 < 0.81), designated sample type B in Fig. 1, has a Tirrad ranging from 1068 to 1434 K (ΔT: 365 K). The central zone of the pellet (0.003 < r/r0 < 0.41), designated sample type C in Fig. 1, which was close to the hottest part of the pellet, has a Tirrad ranging from 1442 to 1572 K (ΔT: 131 K). The sample irradiation temperatures were determined from the calculated temperature profile (exponential function) knowing the core temperature of the fuel (1573 K) [11], the standard temperature for this type of fuel at the inner side of the cladding (800 K). The average burnup was calculated with TRANSURANUS code [12] and the PA burnup is the average burnup multiplied by the ratio of the fissile Pu concentration in PA over average fissile Pu concentration in fuel [11]. Calculated burnups correspond reasonably well with measurement of Walker et al. [11]. All those data are shown Fig. 2.Fragments of 2-8 mg were chosen for the experiments. Since these specimens are small compared to the drilled sample size and were taken randomly, the precise radial position could not be determined, in particular the specimens of sample type, A and B could be from close radial locations.Specimens from each drilled sample type were annealed up to complete vaporisation (˜2600 K) at a speed of about 10 K min-1 in a Knudsen effusion mass spectrometer (KEMS) described previously [13,14]. In addition to helium and to the FGs all the species present in the vapour between 83 and 300 a.m.u. were measured during the heating. Additionally, the 85Kr isotope was analysed in a cold trap by β and γ counting. The long-lived fission gas isotopes correspond to masses 131, 132, 134 and 136 for Xe and 83, 84, 85 and 86 for Kr. The absolute quantities of gas released from specimens of sample types A and B were also determined using the in-house built Q-GAMES (Quantitative gas measurement system), described in detail in [15].For each of the samples, fragments were also annealed and measured in the KEMS up to specific temperatures corresponding to different stages of the FGs or He release. These fragments were subsequently analysed by Scanning Electron Microscopy (SEM, Philips XL40) [16] in order to investigate the relationship between structural changes, burn-up, irradiation temperature and fission products release. SEM observations were also done on the samples before the KEMS experiments and the fracture surface appearance of the samples is shown in Fig. 3, revealing the presence of the high burnup structure (HBS) in the Pu-rich agglomerates.A summary of the 12 samples analysed by KEMS, SEM and Q-GAMES is given in Table 1. At 1300 K no clear change potentially related to gas release appears in the UM and PA. At 1450 K a beginning of grain boundaries opening can be observed as well as rounding of the grains attributed to thermal etching. At 1600 K a densification is observed in the PA, smalls grains seem to agglomerate. At 1800 K grain coalescence has occurred in the PA together with formation of large pores. In the UM one observes the formation of a network of intergranular channels. Finally, at 2100 K re-sintering proceeds further and large intra-granular bubbles and five metal precipitates becomes visible. The micrographs of sample type B at 1700 K in Fig. 10, show the formation of small intergranular channel not observed on the image of the sample type A at 1600 K. At 2200 K the intragranular bubbles and intergranular channel are larger than for the sample type A at 2100 K.Images of sample type C (close to pellet centre) are shown in Fig. 11. The PAs did not show the typical HBS-like restructuring but rather loose (open) grains boundaries attributed to the high irradiation temperature. Also big cavities or very large grain boundaries of ˜10 μm were observed (picture 1). The same structure is observed for the UM. After heating at 1700 K, etching and channel formation at the grain boundaries is observed (pictures 3 and 4) similarly as observed for sample types A and B. At 2300 K the fuel was restructured through grain growth and formation of large cavities and intra-granular bubbles (pictures 5 and 6). No fragmentation of the sample has been observed as in very high burnup UO2 fuel [18].

The Effect of Carbonaceous Reductant Selection on Chromite Pre-reduction

NASA Astrophysics Data System (ADS)

Kleynhans, E. L. J.; Beukes, J. P.; Van Zyl, P. G.; Bunt, J. R.; Nkosi, N. S. B.; Venter, M.

2017-04-01

Ferrochrome (FeCr) production is an energy-intensive process. Currently, the pelletized chromite pre-reduction process, also referred to as solid-state reduction of chromite, is most likely the FeCr production process with the lowest specific electricity consumption, i.e., MWh/t FeCr produced. In this study, the effects of carbonaceous reductant selection on chromite pre-reduction and cured pellet strength were investigated. Multiple linear regression analysis was employed to evaluate the effect of reductant characteristics on the aforementioned two parameters. This yielded mathematical solutions that can be used by FeCr producers to select reductants more optimally in future. Additionally, the results indicated that hydrogen (H)- (24 pct) and volatile content (45.8 pct) were the most significant contributors for predicting variance in pre-reduction and compressive strength, respectively. The role of H within this context is postulated to be linked to the ability of a reductant to release H that can induce reduction. Therefore, contrary to the current operational selection criteria, the authors believe that thermally untreated reductants ( e.g., anthracite, as opposed to coke or char), with volatile contents close to the currently applied specification (to ensure pellet strength), would be optimal, since it would maximize H content that would enhance pre-reduction.

Methotrexate-loaded porous polymeric adsorbents as oral sustained release formulations.

PubMed

Wang, Xiuyan; Yan, Husheng

2017-09-01

Methotrexate as a model drug with poor aqueous solubility was adsorbed into porous polymeric adsorbents, which was used as oral sustained release formulations. In vitro release assay in simulated gastrointestinal fluids showed that the methotrexate-loaded adsorbents showed distinct sustained release performance. The release rate increased with increase in pore size of the adsorbents. In vivo pharmacokinetic study showed that the maximal plasma methotrexate concentrations after oral administration of free methotrexate and methotrexate-loaded DA201-H (a commercial porous polymeric adsorbent) to rats occurred at 40min and 5h post-dose, respectively; and the plasma concentrations decreased to 22% after 5h for free methotrexate and 44% after 24h for methotrexate-loaded DA201-H, respectively. The load of methotrexate into the porous polymeric adsorbents not only resulted in obvious sustained release, but also enhanced the oral bioavailability of methotrexate. The areas under the curve, AUC 0-24 and AUC 0-inf , for methotrexate-loaded DA201-H increased 3.3 and 7.7 times, respectively, compared to those for free methotrexate. Copyright © 2017 Elsevier B.V. All rights reserved.

Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

PubMed

Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

2017-07-24

In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

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.

Influence of soil amendments made from digestate on soil physics and the growth of spring wheat

NASA Astrophysics Data System (ADS)

Dietrich, Nils; Knoop, Christine; Raab, Thomas; Krümmelbein, Julia

2016-04-01

Every year 13 million tons of organic wastes accumulate in Germany. These wastes are a potential alternative for the production of energy in biogas plants, especially because the financial subventions for the cultivation of renewable resources for energy production were omitted in 2014. The production of energy from biomass and organic wastes in biogas plants results in the accumulation of digestate and therefore causes the need for a sustainable strategy of the utilization of these residues. Within the scope of the BMBF-funded project 'VeNGA - Investigations for recovery and nutrient use as well as soil and plant-related effects of digestate from waste fermentation' the application of processed digestate as soil amendments is examined. Therefore we tested four different mechanical treatment processes (rolled pellets, pressed pellets, shredded compost and sieved compost) to produce soil amendments from digestate with regard to their impact on soil physics, soil chemistry and the interactions between plants and soil. Pot experiments with soil amendments were performed in the greenhouse experiment with spring wheat and in field trials with millet, mustard and forage rye. After the first year of the experiment, preliminary results indicate a positive effect of the sieved compost and the rolled pellets on biomass yield of spring wheat as compared to the other variations. First results from the Investigation on soil physics show that rolled pellets have a positive effect on the soil properties by influencing size and distribution of pores resulting in an increased water holding capacity. Further ongoing enhancements of the physical and chemical properties of the soil amendments indicate promising results regarding the ecological effects by increased root growth of spring wheat.

Implementation of a Thermodynamic Solver within a Computer Program for Calculating Fission-Product Release Fractions

NASA Astrophysics Data System (ADS)

Barber, Duncan Henry

During some postulated accidents at nuclear power stations, fuel cooling may be impaired. In such cases, the fuel heats up and the subsequent increased fission-gas release from the fuel to the gap may result in fuel sheath failure. After fuel sheath failure, the barrier between the coolant and the fuel pellets is lost or impaired, gases and vapours from the fuel-to-sheath gap and other open voids in the fuel pellets can be vented. Gases and steam from the coolant can enter the broken fuel sheath and interact with the fuel pellet surfaces and the fission-product inclusion on the fuel surface (including material at the surface of the fuel matrix). The chemistry of this interaction is an important mechanism to model in order to assess fission-product releases from fuel. Starting in 1995, the computer program SOURCE 2.0 was developed by the Canadian nuclear industry to model fission-product release from fuel during such accidents. SOURCE 2.0 has employed an early thermochemical model of irradiated uranium dioxide fuel developed at the Royal Military College of Canada. To overcome the limitations of computers of that time, the implementation of the RMC model employed lookup tables to pre-calculated equilibrium conditions. In the intervening years, the RMC model has been improved, the power of computers has increased significantly, and thermodynamic subroutine libraries have become available. This thesis is the result of extensive work based on these three factors. A prototype computer program (referred to as SC11) has been developed that uses a thermodynamic subroutine library to calculate thermodynamic equilibria using Gibbs energy minimization. The Gibbs energy minimization requires the system temperature (T) and pressure (P), and the inventory of chemical elements (n) in the system. In order to calculate the inventory of chemical elements in the fuel, the list of nuclides and nuclear isomers modelled in SC11 had to be expanded from the list used by SOURCE 2.0. A benchmark calculation demonstrates the improvement in agreement of the total inventory of those chemical elements included in the RMC fuel model to an ORIGEN-S calculation. ORIGEN-S is the Oak Ridge isotope generation and depletion computer program. The Gibbs energy minimizer requires a chemical database containing coefficients from which the Gibbs energy of pure compounds, gas and liquid mixtures, and solid solutions can be calculated. The RMC model of irradiated uranium dioxide fuel has been converted into the required format. The Gibbs energy minimizer has been incorporated into a new model of fission-product vaporization from the fuel surface. Calculated release fractions using the new code have been compared to results calculated with SOURCE IST 2.0P11 and to results of tests used in the validation of SOURCE 2.0. The new code shows improvements in agreement with experimental releases for a number of nuclides. Of particular significance is the better agreement between experimental and calculated release fractions for 140La. The improved agreement reflects the inclusion in the RMC model of the solubility of lanthanum (III) oxide (La2O3) in the fuel matrix. Calculated lanthanide release fractions from earlier computer programs were a challenge to environmental qualification analysis of equipment for some accident scenarios. The new prototype computer program would alleviate this concern. Keywords: Nuclear Engineering; Material Science; Thermodynamics; Radioactive Material, Gibbs Energy Minimization, Actinide Generation and Depletion, FissionProduct Generation and Depletion.

Spray drying of silica microparticles for sustained release application with a new sol-gel precursor.

PubMed

Wang, Bifeng; Friess, Wolfgang

2017-10-30

A new precursor, tetrakis(2-methoxyethyl) orthosilicate (TMEOS) was used to fabricate microparticles for sustained release application, specifically for biopharmaceuticals, by spray drying. The advantages of TMEOS over the currently applied precursors are its water solubility and hydrolysis at moderate pH without the need of organic solvents or catalyzers. Thus a detrimental effect on biomolecular drug is avoided. By generating spray-dried silica particles encapsulating the high molecular weight model compound FITC-dextran 150 via the nano spray dryer Büchi-90, we demonstrated how formulation parameters affect and enable control of drug release properties. The implemented strategies to regulate release included incorporating different quantities of dextrans with varying molecular weight as well as adjusting the pH of the precursor solution to modify the internal microstructures. The addition of dextran significantly altered the released amount, while the release became faster with increasing dextran molecular weight. A sustained release over 35days could be achieved with addition of 60 kD dextran. The rate of FITC-Dextran 150 release from the dextran 60 containing particles decreased with higher precursor solution pH. In conclusion, the new precursor TMEOS presents a promising alternative sol-gel technology based carrier material for sustained release application of high molecular weight biopharmaceutical drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Energy economy of salmon aquaculture in the Baltic sea

NASA Astrophysics Data System (ADS)

Folke, Carl

1988-07-01

Resource utilization in Atlantic salmon aquaculture in the Baltic Sea was investigated by means of an energy analysis. A comparison was made between cage farming and sea ranching enterprises each with yearly yields of 40 t of Atlantic salmon. A variety of sea ranching options were evaluated, including (a) conventional ranching, (b) ranching employing a delayed release to the sea of young smolts, (c) harvesting salmon both by offshore fishing fleets and as they return to coastal areas, and (d) when offshore fishing is banned, harvesting salmon only as they return to coastal areas where released. Inputs both from natural ecosystems (i.e., fish consumed by ranched salmon while in the sea and raw materials used for producing dry food pellets) and from the economy (i.e., fossil fuels and energy embodied in economic goods and services) were quantified in tonnes for food energy and as direct plus indirect energy cost (embodied energy). The fixed solar energy (estimated as primary production) and the direct and indirect auxiliary energy requirements per unit of fish output were expressed in similar units. Similar quantities of living resources in tonnes per unit of salmon biomass output are required whether the salmon are feeding in the sea or are caged farmed. Cage farming is about 10 times more dependent on auxiliary energies than sea ranching. Sea ranching applying delayed release of smolts is 35 45% more efficient in the use of auxiliary energies than conventional sea ranching and cage farming. Restriction of offshore fishing would make sea ranching 3 to 6.5 times more efficient than cage farming. The fixed solar energy input to Atlantic salmon aquaculture is 4 to 63 times larger than the inputs of auxiliary energy. Thus, cage farming and sea ranching are both heavily dependent on the productivity of natural ecosystems. It is concluded that sustainable development of the aquaculture industry must be founded on ecologically integrated technologies which utilize the free production in marine ecosystems without exhausting or damaging the marine environment.

Expanded Analysis of Hot Isostatic Pressed Iodine-Loaded Silver-Exchanged Mordenite

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

Jubin, R. T.; Bruffey, S. H.; Patton, K. K.

2014-09-30

Reduced silver-exchanged mordenite (Ag0Z) is being evaluated as a potential material to control the release of radioactive iodine that is released during the reprocessing of used nuclear fuel into the plant off-gas streams. The purpose of this study was to determine if hot pressing could directly convert this iodine loaded sorbent into a waste form suitable for long-term disposition. The minimal pretreatment required for production of pressed pellets makes hot pressing a technically and economically desirable process. Initial scoping studies utilized hot uniaxial pressing (HUPing) to prepare samples of non-iodine-loaded reduced silver exchanged mordenite (Ag0Z). The resulting samples were verymore » fragile due to the low pressure (~ 28 MPa) used. It was recommended that hot isostatic pressing (HIPing), performed at higher temperatures and pressures, be investigated. HIPing was carried out in two phases, with a third and final phase currently underway. Phase I evaluated the effects of pressure and temperature conditions on the manufacture of a pressed sample. The base material was an engineered form of silver zeolite. Six samples of Ag0Z and two samples of I-Ag0Z were pressed. It was found that HIPing produced a pressed pellet of high density. Analysis of each pressed pellet by scanning electron microscopy-energy dispersive spectrophotometry (SEM-EDS) and X-ray diffraction (XRD) demonstrated that under the conditions used for pressing, the majority of the material transforms into an amorphous structure. The only crystalline phase observed in the pressed Ag0Z material was SiO2. For the samples loaded with iodine (I-Ag0Z) iodine was present as AgI clusters at low temperatures, and transformed into AgIO4 at high temperatures. Surface mapping and EDS demonstrate segregation between silver iodide phases and silicon dioxide phases. Based on the results of the Phase I study, an expanded test matrix was developed to examine the effects of multiple source materials, compositional variations, and an expanded temperature range. Each sample was analyzed with the approach used in Phase I. In all cases, there is nothing in the SEM or XRD analyses that indicates creation of any AgI-containing silicon phase, with the samples being found to be largely amorphous. Phase III of this study has been initiated and is the final phase of scoping tests. It will expand upon the test matrix completed in Phase II and will examine the durability of the pressed pellets through product consistency testing (PCT) studies. Transformation of the component material into a well-characterized iodine-containing mineral phase would be desirable. This would limit the additional experimental testing and modeling required to determine the long-term stability of the pressed pellet, as much of that information has already been learned for several common iodine-containing minerals. However, this is not an absolute requirement, especially if pellets produced by hot isostatic pressing can be demonstrated through initial PCT studies to retain iodine well despite their amorphous composition.« less

Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion.

PubMed

Vo, Anh Q; Feng, Xin; Pimparade, Manjeet; Ye, Xinyou; Kim, Dong Wuk; Martin, Scott T; Repka, Michael A

2017-05-01

In the present study, we aimed to prepare a gastroretentive drug delivery system that would be both highly resistant to gastric emptying via multiple mechanisms and would also potentially induce in situ supersaturation. The bioadhesive floating pellets, loaded with an amorphous solid dispersion, were prepared in a single step of hot-melt extrusion technology. Hydroxypropyl cellulose (Klucel™ MF) and hypromellose (Benecel™ K15M) were used as matrix-forming polymers, and felodipine was used as the model drug. The foam pellets were fabricated based on the expansion of CO 2 , which was generated from sodium bicarbonate during the melt-extrusion process. A 2 n full factorial experimental design was utilized to investigate the effects of formulation compositions to the pellet properties. The melt-extrusion process transformed the crystalline felodipine into an amorphous state that was dispersed and "frozen" in the polymer matrix. All formulations showed high porosity and were able to float immediately, without lag time, on top of gastric fluid, and maintained their buoyancy over 12h. The pellet-specific floating force, which could be as high as 4800μN/g, increased significantly during the first hour, and was relatively stable until 9h. The sodium bicarbonate percentage was found to be most significantly effect to the floating force. The ex vivo bioadhesion force of the pellets to porcine stomach mucosa was approximately 5mN/pellet, which was more than five times higher than the gravitation force of the pellet saturated with water. Drug release was well controlled up to 12h in the sink condition of 0.5% sodium lauryl sulphate in 0.1N HCl. The dissolution at 1, 3, 5, and 8h were 5-12%, 25-45%, 55-80%, and ≥75% respectively for all 11 formulations. In biorelevant dissolution medium, a supersaturated solution was formed, and the concentration was maintained at around 2μg/mL, approximately 10-folds higher than that of the pure felodipine. All input factors significantly affected dissolution in the first 3h, but afterwards, only drug load and hypromellose (HPMC) content had significant effects. The prepared drug delivery system has great potential in overcoming low and fluctuating bioavailability of poorly soluble drugs. Felodipine (PubChem CID: 3333); hypromellose (PubChem CID: 57503849), hydroxypropyl cellulose (PubChem CID: 71306830), sodium bicarbonate (PubChem CID: 516892); sodium carbonate (PubChem CID: 10340). Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and evaluation of sustained release loxoprofen loaded microspheres.

PubMed

Venkatesan, P; Manavalan, R; Valliappan, K

2011-06-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours.

Preparation and evaluation of sustained release loxoprofen loaded microspheres

PubMed Central

Venkatesan, P.; Manavalan, R.; Valliappan, K.

2011-01-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours PMID:24826017

[Sustained release of recombinant human bone morphogenetic protein-2 combined with stromal vascular fraction cells in promoting posterolateral spinal fusion in rat model].

PubMed

Yuan, Wei; Zheng, Jun; Qian, Jinyu; Zhou, Xiaoxiao; Wang, Minghui; Wang, Xiuhui

2017-07-01

To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model. SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and β-tricalcium phosphate (β-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/β-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/β-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high-resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining. The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P <0.05), and in group B than groups A and C ( P <0.05). HE staining, Masson's trichrome staining, and immunohistochemistry staining for OCN staining exhibited a large number of cartilage cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and there was no effective new bone formation in groups A and C. The combination of sustained release of rhBMP-2 and freshly SVFs can significantly promote spinal fusion in rat model, providing a theoretical basis for further clinical applications.

3D Nanoporous Anodic Alumina Structures for Sustained Drug Release

PubMed Central

Xifré-Pérez, Elisabet; Eckstein, Chris; Ferré-Borrull, Josep

2017-01-01

The use of nanoporous anodic alumina (NAA) for the development of drug delivery systems has gained much attention in recent years. The release of drugs loaded inside NAA pores is complex and depends on the morphology of the pores. In this study, NAA, with different three-dimensional (3D) pore structures (cylindrical pores with several pore diameters, multilayered nanofunnels, and multilayered inverted funnels) were fabricated, and their respective drug delivery rates were studied and modeled using doxorubicin as a model drug. The obtained results reveal optimal modeling of all 3D pore structures, differentiating two drug release stages. Thus, an initial short-term and a sustained long-term release were successfully modeled by the Higuchi and the Korsmeyer–Peppas equations, respectively. This study demonstrates the influence of pore geometries on drug release rates, and further presents a sustained long-term drug release that exceeds 60 days without an undesired initial burst. PMID:28825654

Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

PubMed

Bi, Xiu-Zeng; Pan, Wei-Hua; Yu, Xin-Ping; Song, Zong-Ming; Ren, Zeng-Jin; Sun, Min; Li, Cong-Hui; Nan, Kai-Hui

2015-01-01

This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

Management of marine cage aquaculture. Environmental carrying capacity method based on dry feed conversion rate.

PubMed

Cai, Huiwen; Sun, Yinglan

2007-11-01

Marine cage aquaculture produces a large amount of waste that is released directly into the environment. To effectively manage the mariculture environment, it is important to determine the carrying capacity of an aquaculture area. In many Asian countries trash fish is dominantly used in marine cage aquaculture, which contains more water than pellet feed. The traditional nutrient loading analysis is for pellet feed not for trash fish feed. So, a more critical analysis is necessary in trash fish feed culturing areas. Corresponding to FCR (feed conversion rate), dry feed conversion rate (DFCR) was used to analyze the nutrient loadings from marine cage aquaculture where trash fish is used. Based on the hydrodynamic model and the mass transport model in Xiangshan Harbor, the relationship between the water quality and the waste discharged from cage aquaculture has been determined. The environmental carrying capacity of the aquaculture sea area was calculated by applying the models noted above. Nitrogen and phosphorus are the water quality parameters considered in this study. The simulated results show that the maximum nitrogen and phosphorus concentrations were 0.216 mg/L and 0.039 mg/L, respectively. In most of the sea area, the nutrient concentrations were higher than the water quality standard. The calculated environmental carrying capacity of nitrogen and phosphorus in Xiangshan Harbor were 1,107.37 t/yr and 134.35 t/yr, respectively. The waste generated from cage culturing in 2000 has already exceeded the environmental carrying capacity. Unconsumed feed has been identified as the most important origin of all pollutants in cage culturing systems. It suggests the importance of increasing the feed utilization and improving the feed composition on the basis of nutrient requirement. For the sustainable development of the aquaculture industry, it is an effective management measure to keep the stocking density and pollution loadings below the environmental carrying capacity. The DFCR-based nutrient loadings analysis indicates, in trash fish feed culturing areas, that it is more critical and has been proved to be a valuable loading calculation method. The modeling approach for Xiangshan Harbor presented in this paper is a cost-effective method for assessing the environmental impact and determining the capacity. Carrying capacity information can give scientific suggestions for the sustainable management of aquaculture environments. It has been proved that numerical models were convenient tools to predict the environmental carrying capacity. The development of models coupled with dynamic and aquaculture ecology is a requirement of further research. Such models can also be useful in monitoring the ecological impacts caused by mariculture activities.

RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

PubMed

Xing, James Z; Lu, Lei; Unsworth, Larry D; Major, Paul W; Doschak, Michael R; Kaipatur, Neelambar R

2017-02-01

To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala) 4 -CONH 2 [(RADA) 4 ] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth, facilitating the required changes in the surrounding alveolar bone through the process of bone remodelling. The RANKL system regulates alveolar bone remodelling and controls root resorption during OTM. The use of exogenous RANKL to accelerate OTM has not been attempted to date because large quantities of RANKL for systemic therapy may subsequently cause serious systemic loss of skeletal bone. The controlled and sustained local release of RANKL from a carrier matrix could maximize its therapeutic benefit whilst minimizing systemic side effects. In this study a NF-hydrogel was used for sustained and controlled release of RANKL and the release kinetics and biofunctionality of the released RANKL was characterized. Our results provide fundamental insight for further investigating the role of RANKL NF-hydrogel release systems for inducing osteoclastogenesis in vivo. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The use of superoxide mixtures as air-revitalization chemicals in hyperbaric, self-contained, closed-circuit breathing apparatus

NASA Technical Reports Server (NTRS)

Wood, P. C.; Wydeven, T.

1985-01-01

In portable breathing apparatus applications at 1 atm, potassium superoxide (KO2) has exhibited low-utilization efficiency of the available oxygen (O2) and diminished carbon dioxide-(CO2) scrubbing capacity caused by the formation of a fused, hydrated-hydroxide/carbonate product coating on the superoxide granules. In earlier work, it was discovered that granules fabricated from an intimate mixture of KO2 and calcium superoxide, Ca(O2)2, did not exhibit formation of a fused product coating and the utilization efficiency with respect to both O2 release and CO2 absorption was superior to KO2 granules when both types of granules were reacted with humidified CO2 under identified conditions. In the work described here, single pellets of KO2, KO2/Ca(O2), mixtures and commercially available KO2 tables and granules were reacted with a flow of humidified CO2 in helium at 1- and 10-atm total pressure and at an initial temperature of 40 C. In the 1-atm flow tests, the reaction rates and utilization efficiency of the KO2/Ca(O2)2 pellets were markedly superior to the KO2 pellets, tablets, and granules when the samples were reacted under identical conditions. However, at 10 atm, the rates of O2 release and CO2 absorption, as well as the utilization efficiencies of all the superoxide samples, were one-third to one-eighth of the values observed at 1 atm. The decrease in reaction performance at 10 atm compared to that at 1 atm has been attributed principally to the lower bulk diffusivity of the CO2 and H2O reactants in helium at the higher pressure and secondarily to the moderation of the reaction temperature caused by the higher heat capacity of the 10-atm helium.

Modification of crystal habit of ibuprofen using the phase partition technique: effect of aerosil and tween 80 in binding solvent.

PubMed

Umprayn, K; Luengtummuen, A; Kitiyadisai, C; Pornpiputsakul, T

2001-11-01

A ternary diagram, representing the solubility of binding solvent (chloroform) in a mixture of ethanol and water, was constructed. For this study, the solvent mixture that gave the best ibuprofen pellets (IPs) was composed of chloroform.ethanol:water at a ratio of 1.5%:8%:90.5%. The suitable agitator speed, temperature, and mixing time were found to be 1,500 rpm, 25 degrees C +/- 2 degrees C, and 20 min, respectively. In addition, suitable stirring time when the phase partition process of IPs began was 15 min. IPs obtained from these conditions were small and round, approximately 1 mm; surface determination by scanning electron microscopy (SEM) indicated that the IPs were composed of drug microcrystals rearranged on the surface. For the dissolution, IPs showed lower drug release when compared with pure ibuprofen crystal (IC) (f2 analysis). An attempt to modify the dissolution property of IP by incorporating various concentrations of Aerosil and Tween 80 in the binding solvent was made. Microscopic appearance showed that both Aerosil and Tween 80 gave less spherical pellets when compared with the use of binding solvent alone. For both the Aerosil and Tween 80 employed, the results indicated a change in rearrangement of drug microcrystals and a change in crystal habit. However, Tween 80 gave more change of the crystallographic direction of drug microcrystals than Aerosil. In term of dissolution, the results showed that employing Tween 80 at 1.2% gave the highest drug release compared to the use of Aerosil and IC alone (f2 analysis). These pellets had a good flow property, as indicated by Carr's compressibility, flow rate, and angle of repose, and they can be compressed into a tablet, encapsulated by suitable polymer, or pulverized to obtain micronized crystals. In the case of compression into tablets, the dissolution profiles of these tablets compared with those of commercial product meet the USP 24 requirement (Q > or = 80% at 60 min).

Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability.

PubMed

Ahmed, Tarek A; Ibrahim, Hany M; Samy, Ahmed M; Kaseem, Alaa; Nutan, Mohammad T H; Hussain, Muhammad Delwar

2014-06-01

The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueous medium, the PLGA in ISI and ISM systems solidified resulting in implants and microparticles, respectively. The in vitro drug release from the ISI system showed marked difference from miscible solvents (NMP and DMSO) than the partially miscible ones (triacetin and ethyl acetate), and the drug release decreased with increased PLGA concentration. In the ISM system, the initial in vitro drug release decreased with decreased ratio of polymer phase to external oil phase. In vivo studies in rats showed that ISM had slower drug release than the drug release from ISI. Also, the ISM system when compared to ISI system had significantly reduced initial burst effect. In vitro as well as the in vivo studies for both ISI and ISM systems showed sustained release of MK. The ISM system is suitable for sustained release of MK over 4-week period with a lower initial burst compared to the ISI system. Stability studies of the ISI and ISM formulations showed that MK is stable in the formulations stored at 4°C for more than 2 years.

Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

PubMed

Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2017-01-01

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of formulation and process variables on lipid based sustained release tablets via continuous twin screw granulation: A comparative study.

PubMed

Kallakunta, Venkata Raman; Tiwari, Roshan; Sarabu, Sandeep; Bandari, Suresh; Repka, Michael A

2018-05-14

The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous twin-screw granulation process with a low proportion of binder (Klucel™ EF, HPC SSL) using Compritol® 888 ATO, Precirol® ATO 5 and Geleol™ as sustained release agents. The granules prepared showed good flow characteristics and compaction properties. DSC and XRD studies were conducted to characterize the granules prepared via a twin-screw granulation method and the results demonstrated the crystalline nature of lipids within the granules. FTIR data indicated that there were no interactions with the formulation components investigated. The formulations developed by all three methods were compressed into tablets with a mechanical strength of 14-16 KP. The tablets formulated were characterized for physicochemical properties, in vitro drug release studies, water uptake and erosion studies. These results showed that the drug was not completely released after 24 h for tablets developed by the wet granulation process using all three lipids. The tablets prepared by the direct compression method demonstrated a burst release within 8 to 10 h from Precirol ATO 5® and Geleol™ formulations compared to Compritol® 888 ATO. However, tablets prepared using twin-screw granulation exhibited sustained release of the drug over 24 h and the water uptake and erosion results were in accordance with dissolution data. Stability data for 45 days at accelerated conditions (40 °C/75% RH) showed similar release profiles with ƒ2 values above 50 for all of the twin screw granulation formulations, indicating the suitability of the process for formulating sustained release tablets. These findings of a single-step, continuous twin-screw granulation process are novel and demonstrate new opportunities for development of sustained release tablets. Copyright © 2017. Published by Elsevier B.V.

Chiral separation of isoxanthohumol and 8-prenylnaringenin in beer, hop pellets, and hops by HPLC with chiral columns.

PubMed

Moriya, Hyuga; Tanaka, Sohei; Iida, Yukari; Kitagawa, Satomi; Aizawa, Sen-Ichi; Taga, Atsushi; Terashima, Hiroyuki; Yamamoto, Atsushi; Kodama, Shuji

2018-05-16

Xanthohumol, isoxanthohumol, and 8-prenylnaringenin in beer, hop, and hop pellet samples were analyzed by HPLC using InertSustain phenyl column and the mobile phase containing 40% methanol and 12% 2-propanol. Fractions of isoxanthohumol and 8-prenylnaringenin obtained by the above HPLC were separately collected. Isoxanthohumol and 8-prenylnaringenin were enantioseparated by HPLC using Chiralcel OD-H column with a mobile phase composed of hexane/ethanol (90/10, v/v) and Chiralpak AD-RH column with a mobile phase composed of methanol/2-propanol/water (40/20/40, v/v/v), respectively. Both of isoxanthohumol and 8-prenylnaringenin from beer, hop, and hop pellet samples were found to be a racemic mixture. This can be explained that the two analytes were produced by non-enzymatic process. The effects of boiling conditions on the conversion of xanthohumol into isoxanthohumol were also studied. A higher concentration of ethanol in heating solvent resulted in a decrease in the conversion ratio and the conversion was stopped by addition of ethanol more than 50% (v/v). The isomerization was significantly affected pH (2-10) and the boiling medium at pH 5 was minimum for the conversion. Therefore, it was suggested that xanthohumol was relatively difficult to convert to isoxanthohumol in wort (pH 5-5.5) during boiling. This article is protected by copyright. All rights reserved.

Concentrate minimization and water recovery enhancement using pellet precipitator in a reverse osmosis process treating textile wastewater.

PubMed

Sahinkaya, Erkan; Sahin, Ahmet; Yurtsever, Adem; Kitis, Mehmet

2018-06-09

Industrial wastewater reuse together with zero or near zero liquid discharges have been a growing trend due to the requirement of sustainable water management mandated by water scarcity and tightening discharge regulations. Studies have been conducted on the reclamation of textile industry wastewater using RO processes. However a lot of scientific attention has been drawn upon limiting the amount of concentrate generated from RO processes, which depends on the concentrations of scale forming ions in the concentrate stream. Hence, this study aims at investigating the applicability of an ultra-filtration (UF) membrane integrated pellet reactor to remove scale forming ions, i.e. Ca 2+ , Mg 2+ and Si from the concentrate of a pilot-scale textile industry RO process, for the first time in the literature. The resulting effluent was further tested in a secondary RO process to decrease concentrate volume and increase total water recovery. The pellet reactor operated at an extremely low hydraulic retention time of 0.1 h removed scale forming ions, i.e. Ca 2+ , Mg 2+ , with 90-95% efficiency, which improved the secondary RO process performance up to 92-94% overall water recovery, i.e. near zero liquid discharge was reached. Ozonation of the concentrate partially removed COD and color, which further improved the secondary RO filtration performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of feeding on the plasma disposition kinetics of the anthelmintic albendazole in laying hens.

PubMed

Bistoletti, M; Alvarez, L; Lanusse, C; Moreno, L

2014-01-01

1. To optimise the use of albendazole (ABZ) as an anthelmintic in hens, the effects of fasting and type of diet on the plasma kinetics of ABZ and its metabolites were evaluated. 2. Twenty-four hens were distributed into 4 groups: In experiment I the Fed group were fed ad libitum, while the Fasted group was fasted over a 12-h period. In experiment II the Pelleted group was fed with pelleted commercial food, while the Grain group was fed with cereal grains. All the groups were treated with ABZ by oral route. Blood samples were taken and plasma analysed by HPLC. 3. ABZ and its metabolites albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) were recovered in plasma in all the groups. The 12-h fasting period did not modify the disposition kinetics of ABZ in hens. The type of feed affected ABZ kinetics. ABZSO concentration profile was higher and detected for longer in the Grain group compared to the Pelleted group. Statistical differences were not found for AUC0-∞ values, whereas the T1/2for and T1/2el were different between groups. 4. Factors affecting ABZ kinetic behaviour should be taken into account to optimise its use to ensure the sustainability of the limited available anthelmintic therapeutic tools in avian parasite control.

Effect of hydrothermal carbonization on storage process of woody pellets: Pellets' properties and aldehydes/ketones emission.

PubMed

Li, Hui; Wang, Siyuan; Huang, Zhongliang; Yuan, Xingzhong; Wang, Ziliang; He, Rao; Xi, Yanni; Zhang, Xuan; Tan, Mengjiao; Huang, Jing; Mo, Dan; Li, Changzhu

2018-07-01

Effect of hydrothermal carbonization (HTC) on the hydrochar pelletization and the aldehydes/ketones emission from pellets during storage was investigated. Pellets made from the hydrochar were stored in sealed apparatuses for sampling. The energy consumption during pelletization and the pellets' properties before/after storage, including dimension, density, moisture content, hardness, aldehyde/ketones emission amount/rate and unsaturated fatty acid amount, were analyzed. Compared with untreated-sawdust-pellets, the hydrochar-pellets required more energy consumption for pelletization, and achieved the improved qualities, resulting in the higher stability degree during storage. The species and amount of unsaturated fatty acids in the hydrochar-pellets were higher than those in the untreated-sawdust-pellets. The unsaturated fatty acids content in the hydrochar-pellets was decreased with increasing HTC temperature. Higher aldehydes/ketones emission amount and rates with a longer emission period were found for the hydrochar-pellets, associated with variations of structure and unsaturated fatty acid composition in pellets. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Matrix tablets for sustained release of repaglinide: Preparation, pharmacokinetics and hypoglycemic activity in beagle dogs.

PubMed

He, Wei; Wu, Mengmeng; Huang, Shiqing; Yin, Lifang

2015-01-15

Repaglinide (RG) is an efficient antihyperglycemic drug; however, due to its short half-life, patients are required to take the marketed products several times a day, which compromises the therapeutic effects. The present study was conducted to develop a hydrophilic sustained release matrix tablet for RG with the aims of prolonging its action time, reducing the required administration times and side effects and improving patient adherence. The matrix tablets were fabricated by a direct compression method, the optimized formulation for which was obtained by screening the factors that affected the drug release. Moreover, studies of the pharmacokinetics and hypoglycemic activity as measured by glucose assay kits were performed in dogs. Sustained drug releases profiles over 10h and a reduced influence of medium pHs on release were achieved with the optimized formulation; moreover, the in vivo performance of extended release formulation was also examined, and better absorption, a one-fold decrease in Cmax, a two-fold increase of Tmax and a prolonged hypoglycemic effect compared to the marketed product were observed. In conclusion, sustained RG release and prolonged action were observed with present matrix tablets, which therefore provide a promising formulation for T2D patients who require long-term treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Retardation of Antigen Release from DNA Hydrogel Using Cholesterol-Modified DNA for Increased Antigen-Specific Immune Response.

PubMed

Umeki, Yuka; Saito, Masaaki; Takahashi, Yuki; Takakura, Yoshinobu; Nishikawa, Makiya

2017-10-01

Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction-based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol-modified DNA and urea-denatured OVA (udOVA). Cholesterol-modified DNA forms a hydrogel, Dgel(chol), and induces IL-6 mRNA expression in mouse skin after intradermal injection, as DNA without cholesterol does. Cholesterol-modified DNA associated with OVA and denaturation of OVA using urea increases the interaction. The release of udOVA from Dgel(chol) is significantly slower than that from DNA hydrogel with no cholesterol, Dgel. Moreover, intratumoral injections of udOVA/Dgel(chol) significantly inhibit the growth of EG7-OVA tumors in mice. These results indicate that sustained release of antigen from Dgel can be achieved by the combination of urea denaturation and cholesterol modification, and retardation of antigen release is effective to induce antigen-specific cancer immunity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glucosamine Inhibits Decidualization of Human Endometrial Stromal Cells and Decreases Litter Sizes in Mice1

PubMed Central

Tsai, Jui-He; Schulte, Maureen; O'Neill, Kathleen; Chi, Maggie M.-Y.; Frolova, Antonina I.; Moley, Kelle H.

2013-01-01

ABSTRACT Embryo implantation in the uterus depends on decidualization of the endometrial stromal cells (ESCs), and glucose utilization via the pentose phosphate pathway is critical in this process. We hypothesized that the amino sugar glucosamine may block the pentose phosphate pathway via inhibition of the rate-limiting enzyme glucose-6-phosphate dehydrogenase in ESCs and therefore impair decidualization and embryo implantation, thus preventing pregnancy. Both human primary and immortalized ESCs were decidualized in vitro in the presence of 0, 2.5, or 5 mM glucosamine for 9 days. Viability assays demonstrated that glucosamine was well tolerated by human ESCs. Exposure of human ESCs to glucosamine resulted in significant decreases in the activity and expression of glucose-6-phosphate dehydrogenase and in the mRNA expression of the decidual markers prolactin, somatostatin, interleukin-15, and left-right determination factor 2. In mouse ESCs, expression of the decidual marker Prp decreased upon addition of glucosamine. In comparison with control mice, glucosamine-treated mice showed weak artificial deciduoma formation along the stimulated uterine horn. In a complementary in vivo experiment, a 60-day-release glucosamine (15, 150, or 1500 μg) or placebo pellet was implanted in a single uterine horn of mice. Mice with a glucosamine pellet delivered fewer live pups per litter than those with a control pellet, and pup number returned to normal after the end of the pellet-active period. In conclusion, glucosamine is a nonhormonal inhibitor of decidualization of both human and mouse ESCs and of pregnancy in mice. Our data indicate the potential for development of glucosamine as a novel, reversible, nonhormonal contraceptive. PMID:23718985

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

Spencer, B. W.; Williamson, R. L.; Stafford, D. S.

One of the important roles of cladding in light water reactor fuel rods is to prevent the release of fission products. To that end, it is essential that the cladding maintain its integrity under a variety of thermal and mechanical loading conditions. Local geometric irregularities in fuel pellets caused by manufacturing defects known as missing pellet surfaces (MPS) can in some circumstances lead to elevated cladding stresses that are sufficiently high to cause cladding failure. Accurate modeling of these defects can help prevent these types of failures. The BISON nuclear fuel performance code developed at Idaho National Laboratory can bemore » used to simulate the global thermo-mechanical fuel rod behavior, as well as the local response of regions of interest, in either 2D or 3D. In either case, a full set of models to represent the thermal and mechanical properties of the fuel, cladding and plenum gas is employed. A procedure for coupling 2D full-length fuel rod models to detailed 3D models of the region of the rod containing a MPS defect is detailed in this paper. The global and local model each contain appropriate physics and behavior models for nuclear fuel. This procedure is demonstrated on a simulation of a boiling water reactor (BWR) fuel rod containing a pellet with an MPS defect, subjected to a variety of transient events, including a control blade withdrawal and a ramp to high power. The importance of modeling the local defect using a 3D model is highlighted by comparing 3D and 2D representations of the defective pellet region. Finally, parametric studies demonstrate the effects of the choice of gaseous swelling model and of the depth and geometry of the MPS defect on the response of the cladding adjacent to the defect.« less

Influence of pellet diameter and length on the quality of pellets and performance, nutrient utilisation and digestive tract development of broilers fed on wheat-based diets.

PubMed

Abdollahi, M R; Ravindran, V; Wester, T J; Ravindran, G; Thomas, D V

2013-06-01

1. The influence of pellet diameter and length on the quality of pellets and performance, nutrient utilisation and digestive tract development of broilers given wheat-based diets was examined from 10 to 42 d of age. The experimental design was a 2 × 2 factorial arrangement of treatments evaluating two pellet diameters (3 and 4.76 mm) and two pellet lengths (3 and 6 mm). From 0 to 9 d of age, all birds were offered a common starter diet pelleted with a 3-mm diameter die and 3-mm length. Broiler grower (d 10 to 21) and finisher (d 22 to 42) diets, based on wheat, were formulated and then subjected to the 4 different treatments. 2. In grower diets, increasing pellet diameter and pellet length reduced the gelatinised starch (GS) content of the diets. In finisher diets, GS content of 3-mm diameter pellets did not change with increasing pellet length but decreased in 4.76-mm diameter pellets. 3. In grower and finisher diets, increments in intact pellet weight, pellet durability index and pellet hardness with increasing pellet length were greater in 3-mm diameter pellets than those with 4.76-mm diameter. 4. Increasing pellet length from 3 to 6 mm increased apparent metabolisable energy values. Neither the interaction nor main effects were significant for the ileal digestibility of nitrogen and starch. 5. During the grower period (d 10 to 21), birds given pellets of 6-mm length had greater body-weight gain than those given 3-mm length pellets. Feeding 6-mm length pellets decreased feed per body-weight gain compared to 3-mm length pellets. During the finisher (d 22 to 42) and whole grow-out (d 10 to 42) periods, while different pellet lengths had no effect on feed per body-weight gain values at 3-mm pellet diameter, increasing the pellet length decreased feed per body-weight gain at 4.76-mm pellet diameter. 6. Increasing pellet diameter and pellet length reduced the relative length of duodenum. Birds given 3-mm diameter pellets had heavier proventriculus compared to those given 4.76-mm diameter pellets. 7. Overall, the data suggest that increasing the pellet length from 3 to 6 mm improved the body-weight gain and feed per body-weight gain during the grower period (d 10 to 21). While the positive effect on body-weight gain disappeared as the birds grew older, improvements in feed per body-weight gain were maintained over the finisher and whole grow-out periods only in 4.76-mm diameter pellets. Small diameter die holes and longer pellet lengths may be considered as potential manipulations to manufacture high-quality pellets under low conditioning temperatures.

Effect of glycerol on sustained insulin release from PVA hydrogels and its application in diabetes therapy

PubMed Central

Cai, Yunpeng; Che, Junyi; Yuan, Minglu; Shi, Xiaohong; Chen, Wei; Yuan, Wei-En

2016-01-01

The present study aimed to investigate the effects of glycerol on the physical properties and release of an insulin-loaded polyvinyl alcohol (PVA) hydrogel film. The insulin-loaded hydrogel composite film was produced using the freeze-thawing method, after which the in vitro swelling ratio, transmittance and insulin release, and the in vivo pharmacodynamics, of hydrogels containing various volumes of glycerol were investigated. The results demonstrated that the addition of glycerol reduced the swelling ratio and increased the softness of the PVA hydrogel film. An analysis of insulin release in vitro and of the hypoglycemic effects in rats demonstrated that the PVA hydrogel film had a sustained release of insulin and long-acting effect over 10 days. The results of the present study suggested that, as a hydrophilic plasticizer, glycerol was able to enhance the release of insulin in the early stage of release profile by enhancing the formation of water channels, although the total swelling ratio was decreased. Therefore, the insulin-loaded glycerol/PVA hydrogel film may be a promising sustained-release preparation for the treatment of diabetes. PMID:27698690

Serum Albumin Beads: An Injectable, Biodegradable System for the Sustained Release of Drugs

NASA Astrophysics Data System (ADS)

Lee, Timothy K.; Sokoloski, Theodore D.; Royer, Garfield P.

1981-07-01

Biologically active compounds were entrapped in cross-linked serum albumin microbeads. Injection of these drug-impregnated beads into rabbits produced no adverse immunological reactions. Sustained release (20 days) of progesterone was demonstrated in vivo.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Plasmodium falciparum polypeptides released during in vitro cultivation*

PubMed Central

Da Silva, L. Rodriguez; Loche, M.; Dayal, R.; Perrin, L. H.

1983-01-01

Synchronous cultures of Plasmodium falciparum were successively labelled with (35S)-methionine and both the supernatants and the pellets of infected red blood cells were collected. The release of TCA-precipitable material in the culture supernatants was low during the development of ring forms and trophozoites, increased during schizogony, and was maximum at the time of schizont rupture and merozoite reinvasion. Analysis of the supernatants by SDS — PAGE and autoradiography showed that both polypeptides common to the various developmental stages of the parasite and schizont/merozoite-specific polypeptides were released. Polypeptides of relative molecular mass 140 000, 82 000 and, to a lower degree, 41 000 were present in high amounts in the culture supernatants. These polypeptides have been shown to be the target of monoclonal antibodies that are able to inhibit the growth of P. falciparum cultures, and may be involved in protective immunity. The released polypeptides may also be used as target antigens in immunodiagnostic tests aiming at the detection of malaria infection. ImagesFig. 2AFig. 2BFig. 3 PMID:6340846

Insights on wood combustion generated proinflammatory ultrafine particles (UFP).

PubMed

Corsini, Emanuela; Ozgen, Senem; Papale, Angela; Galbiati, Valentina; Lonati, Giovanni; Fermo, Paola; Corbella, Lorenza; Valli, Gianluigi; Bernardoni, Vera; Dell'Acqua, Manuela; Becagli, Silvia; Caruso, Donatella; Vecchi, Roberta; Galli, Corrado L; Marinovich, Marina

2017-01-15

This study aimed to collect, characterize ultrafine particles (UFP) generated from the combustion of wood pellets and logs (softwood and hardwood) and to evaluate their pro-inflammatory effects in THP-1 and A549 cells. Both cell lines responded to UFP producing interleukin-8 (IL-8), with wood log UFP being more active compared to pellet UFP. With the exception of higher effect observed with beech wood log UFP in THP-1, the ability of soft or hard woods to induce IL-8 release was similar. In addition, on weight mass, IL-8 release was similar or lower compared to diesel exhaust particles (DEP), arguing against higher biological activity of smaller size particles. UFP-induced IL-8 could be reduced by SB203580, indicating a role of p38MAPK activation in IL-8 production. The higher activity of beech wood log UFP in THP-1 was not due to higher uptake or endotoxin contamination. Qualitatively different protein adsorption profiles were observed, with less proteins bound to beech UFP compared to conifer UFP or DEP, which may provide higher intracellular availability of bioactive components, i.e. levoglucosan and galactosan, toward which THP-1 were more responsive compared to A549 cells. These results contribute to our understanding of particles emitted by domestic appliances and their biological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Current strategies for sustaining drug release from electrospun nanofibers

PubMed Central

Chou, Shih-Feng; Carson, Daniel; Woodrow, Kim A.

2017-01-01

Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically < 1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning. PMID:26363300

Current strategies for sustaining drug release from electrospun nanofibers.

PubMed

Chou, Shih-Feng; Carson, Daniel; Woodrow, Kim A

2015-12-28

Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning. Copyright © 2015 Elsevier B.V. All rights reserved.

Oral controlled release optimization of pellets prepared by extrusion-spheronization processing.

PubMed

Bianchini, R; Vecchio, C

1989-06-01

Controlled release high dosage forms of a typical drug such as Indobufen were prepared as multiple-unit doses by employing extrusion-spheronization processing and subsequently film coating operations. The effects of drug particle size, drug/binder ratio, extruder screen size and preparation reproducibility on the physical properties of the spherical granules were evaluated. Controlled release optimization was obtained on the same granules by coating with polymeric membranes of different thickness consisting of water-soluble and insoluble substances. Film coating was applied from an organic solution using pan coating technique. The drug diffusion is allowed by dissolution of part of the membrane leaving small channels of the polymer coat. Further preparations were conducted to evaluate coatings applied from aqueous dispersion (pseudolatex) using air suspension coating technique. In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The most promising preparations having the desired in vitro release, were metered into hard capsules to obtain the drug unit dosage. Accelerated stability tests were carried out to assess the influence of time and the other storage parameters on the drug release profile.

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Sustained-release subconjunctival 5-fluorouracil.

PubMed

Smith, T J; Ashton, P

1996-09-01

The purpose of this research was to obtain preliminary safety and efficacy data on a novel sustained-release 5-fluorouracil (5-FU) implant in high-risk glaucoma surgical patients. The implants were placed subconjunctivally in four patients undergoing high-risk trabeculectomy. The patients have been observed for approximately 2.5 years. In three of the four patients intraocular pressure was controlled at less than 21 mm Hg, with stabilization of the visual field. One patient had early failure. No untoward events were linked to the placement of the implant. Sustained-release systems for subconjunctival 5-FU may be useful in filter maintenance.

Oral Sustained Release of a Hydrophilic Drug Using the Lauryl Sulfate Salt/Complex.

PubMed

Kasashima, Yuuki; Yoshihara, Keiichi; Yasuji, Takehiko; Sako, Kazuhiro; Uchida, Shinya; Namiki, Noriyuki

2016-01-01

The objective of this study was to establish the key factor of the lauryl sulfate (LS) salt/complex for sustained release of a hydrophilic drug at various physiological pH levels. Mirabegron is a hydrophilic drug that exhibits pH-dependent solubility. Sodium lauryl sulfate (SLS) bound to mirabegron in a stoichiometric manner. The formation of the LS salt/complex significantly reduced mirabegron solubility and helped achieve sustained release of mirabegron over a wide range of pH levels. In addition to SLS, other additives containing a sulfate group formed salts/complexes with mirabegron and reduced its solubility at different pH levels. Furthermore, octyl sulfate (OS), myristyl sulfate (MS), and cetyl sulfate (CS) salts/complexes, which contain alkyl chains of different lengths, showed a lower solubility than mirabegron and promoted sustained release of mirabegron. The rank order of solubility and dissolution rate were as follows: OS salt/complex>LS salt/complex>MS salt/complex>CS salt/complex, which corresponded to the rank of alkyl chain lengths. We conclude that the presence of a sulfate group and the length of the alkyl chain are key factors of the LS salt/complex for sustained release of a hydrophilic drug at various physiological pH levels.

Possibilities for preservation of coarse particles in pelleting process to improve feed quality characteristics.

PubMed

Vukmirović, D; Fišteš, A; Lević, J; Čolović, R; Rakić, D; Brlek, T; Banjac, V

2017-10-01

Poultry diets are mainly used in pelleted form because pellets have many advantages compared to mash feed. On the other hand, pelleting causes reduction of feed particle size. The aim of this research was to investigate the possibility of increasing the content of coarse particles in pellets, and, at the same time, to produce pellets with satisfactory quality. In this research, the three grinding treatments of corn were applied using hammer mill with three sieve openings diameter: 3 mm (HM-3), 6 mm (HM-6) and 9 mm (HM-9). These grinding treatments were combined in pelleting process with three gaps between rollers and the die of pellet press (roller-die gap, RDG) (0.30, 1.15 and 2.00 mm) and three moisture contents of the pelleted material (14.5, 16.0 and 17.5%). The increased coarseness of grinding by the hammer mill resulted in the increased amount of coarse particles in pellets, especially when the smallest RDG was applied (0.30 mm), but pellet quality was greatly reduced. Increasing of RDG improved the quality of pellets produced from coarsely ground corn, but reduced the content of coarse particles in pellets and increased specific energy consumption of the pellet press. Increasing the moisture content of material to be pelleted (MC) significantly reduced energy consumption of the pellet press, but there was no significant influence of MC on particle size after pelleting and on the pellet quality. The optimal values of the pelleting process parameters were determined using desirability function method. The results of optimization process showed that to achieve the highest possible quantity of coarse particles in the pellets, and to produce pellets of satisfactory quality, with the lowest possible energy consumption of the pellet press, the coarsest grinding on hammer mill (HM-9), the largest RDG (2 mm) and the highest MC (17.5%) should be applied. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Investigation on influence of Wurster coating process parameters for the development of delayed release minitablets of Naproxen.

PubMed

Shah, Neha; Mehta, Tejal; Aware, Rahul; Shetty, Vasant

2017-12-01

The present work aims at studying process parameters affecting coating of minitablets (3 mm in diameter) through Wurster coating process. Minitablets of Naproxen with high drug loading were manufactured using 3 mm multi-tip punches. The release profile of core pellets (published) and minitablets was compared with that of marketed formulation. The core formulation of minitablets was found to show similarity in dissolution profile with marketed formulation and hence was further carried forward for functional coating over it. Wurster processing was implemented to pursue functional coating over core formulation. Different process parameters were screened and control strategy was applied for factors significantly affecting the process. Modified Plackett Burman Design was applied for studying important factors. Based on the significant factors and minimum level of coating required for functionalization, optimized process was executed. Final coated batch was evaluated for coating thickness, surface morphology, and drug release study.

Redefining the Breast Cancer Exosome Proteome by Tandem Mass Tag Quantitative Proteomics and Multivariate Cluster Analysis.

PubMed

Clark, David J; Fondrie, William E; Liao, Zhongping; Hanson, Phyllis I; Fulton, Amy; Mao, Li; Yang, Austin J

2015-10-20

Exosomes are microvesicles of endocytic origin constitutively released by multiple cell types into the extracellular environment. With evidence that exosomes can be detected in the blood of patients with various malignancies, the development of a platform that uses exosomes as a diagnostic tool has been proposed. However, it has been difficult to truly define the exosome proteome due to the challenge of discerning contaminant proteins that may be identified via mass spectrometry using various exosome enrichment strategies. To better define the exosome proteome in breast cancer, we incorporated a combination of Tandem-Mass-Tag (TMT) quantitative proteomics approach and Support Vector Machine (SVM) cluster analysis of three conditioned media derived fractions corresponding to a 10 000g cellular debris pellet, a 100 000g crude exosome pellet, and an Optiprep enriched exosome pellet. The quantitative analysis identified 2 179 proteins in all three fractions, with known exosomal cargo proteins displaying at least a 2-fold enrichment in the exosome fraction based on the TMT protein ratios. Employing SVM cluster analysis allowed for the classification 251 proteins as "true" exosomal cargo proteins. This study provides a robust and vigorous framework for the future development of using exosomes as a potential multiprotein marker phenotyping tool that could be useful in breast cancer diagnosis and monitoring disease progression.

A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

PubMed

Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

2016-11-20

During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation and in vitro characterization of xanthan gum-based sustained release matrix tables of isosorbide-5- mononitrate.

PubMed

Kar, Rajat; Mohapatra, Snehamayee; Bhanja, Satyabrata; Das, Debjyoti; Barik, Bhaktibhusan

2010-01-01

In the present investigation an attempt has been made to increase therapeutic efficacy, to reduce frequency of administration and to improve patient compliance by developing a sustained release matrix tablets of isosorbide-5-mononitrate. Sustained release matrix tablets of isosorbide-5-mononitrate were developed by using different drug: polymer ratios, such in F1 (1:0.75), F2 (1:1), F3 (1:1.5), F4 (1:1.75) and F6 (1:2). Xanthan gum was used as matrix former and microcrystalline cellulose as diluent. All the lubricated formulations were compressed, using 8mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution study using basket method and swelling index. Each formulation showed compliance with pharmacopoeial standards. Among all formulations, F5 showed a greater sustained release pattern of drug over a 12 h period with 92.12% of drug being released. The kinetic studies showed that drug release follows the Higuchi model (r(2) =0.9851). Korsemeyer and Peppas equation gave an n-value of 0.4566, which was close to 0.5, indicating that drug release follows the Fickian diffusion. Thus, xanthan gum can be used as an effective matrix former to extend the release of isosorbide-5-mononitrate. No significant difference was observed in the dissolution profile of optimized formulation, using basket and paddle apparatus.

Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate.

PubMed

Biswas, Nikhil; Sahoo, Ranjan Kumar

2016-02-01

The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51-58% entrapped MT showed 90% release within 45 min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3-4 h. A 12% w/w HPMC coating on these beads extended the release upto 9-11 h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12 h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11 h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12 h. Copyright © 2015 Elsevier B.V. All rights reserved.

46 CFR 148.04-21 - Coconut meal pellets (also known as copra pellets).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Coconut meal pellets (also known as copra pellets). 148.04-21 Section 148.04-21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... § 148.04-21 Coconut meal pellets (also known as copra pellets). (a) Coconut meal pellets; (1) Must...

A diels-alder modulated approach to control and sustain the release of dexamethasone and induce osteogenic differentiation of human mesenchymal stem cells

PubMed Central

Koehler, Kenneth C.; Alge, Daniel L.; Anseth, Kristi S.; Bowman, Christopher N.

2013-01-01

We report a new approach to controlled drug release based upon exploiting the dynamic equilibrium that exists between Diels-Alder reactants and products, demonstrating the release of a furan containing dexamethasone peptide (dex-KGPQG-furan) from a maleimide containing hydrogel. Using a reaction-diffusion model, the release kinetics were tuned to achieve sustained concentrations conducive to osteogenic differentiation of human mesenchymal stem cells (hMSCs). Efficacy was first demonstrated in a 2D culture model, in which dexamethasone release induced significant increases in alkaline phosphatase (ALP) activity and mineral deposition in hMSCs compared to a dexamethasone-free treatment. The results were similar to that observed with a soluble dexamethasone treatment. More dramatic differences were observed in 3D culture, where co-encapsulation of a dexamethasone releasing hydrogel depot within an hMSC-laden extracellular matrix mimetic poly(ethylene glycol) hydrogel resulted in a local and robust osteogenic differentiation. ALP activity reached levels that were up to six times higher than the dexamethasone free treatment. Interestingly, at 5 and 10 day time points, the ALP activity exceeded the dexamethasone positive control, suggesting a potential benefit of sustained release in 3D culture. After 21 days, substantial mineralization comparable to the positive control was also observed in the hydrogels. Collectively, these results demonstrate Diels-Alder modulated release as an effective and versatile new platform for controlled drug delivery that may prove especially beneficial for sustaining the release of low molecular weight molecules in hydrogel systems. PMID:23465826

Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

PubMed Central

Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

2015-01-01

Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. Conclusion In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy. PMID:26035710

46 CFR 148.325 - Wood chips; wood pellets; wood pulp pellets.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Wood chips; wood pellets; wood pulp pellets. 148.325... § 148.325 Wood chips; wood pellets; wood pulp pellets. (a) This part applies to wood chips and wood pulp... cargo hold. (b) No person may enter a cargo hold containing wood chips, wood pellets, or wood pulp...

46 CFR 148.325 - Wood chips; wood pellets; wood pulp pellets.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Wood chips; wood pellets; wood pulp pellets. 148.325... § 148.325 Wood chips; wood pellets; wood pulp pellets. (a) This part applies to wood chips and wood pulp... cargo hold. (b) No person may enter a cargo hold containing wood chips, wood pellets, or wood pulp...

46 CFR 148.325 - Wood chips; wood pellets; wood pulp pellets.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Wood chips; wood pellets; wood pulp pellets. 148.325... § 148.325 Wood chips; wood pellets; wood pulp pellets. (a) This part applies to wood chips and wood pulp... cargo hold. (b) No person may enter a cargo hold containing wood chips, wood pellets, or wood pulp...

46 CFR 148.325 - Wood chips; wood pellets; wood pulp pellets.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Wood chips; wood pellets; wood pulp pellets. 148.325... § 148.325 Wood chips; wood pellets; wood pulp pellets. (a) This part applies to wood chips and wood pulp... cargo hold. (b) No person may enter a cargo hold containing wood chips, wood pellets, or wood pulp...

Twin-Screw Extruder and Pellet Accelerator Integration Developments for ITER

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

Meitner, Steven J; Baylor, Larry R; Combs, Stephen Kirk

The ITER pellet injection system consisting of a twinscrew frozen hydrogen isotope extruder, coupled to a combination solenoid actuated pellet cutter and pneumatic pellet accelerator, is under development at the Oak Ridge National Laboratory. A prototype extruder has been built to produce a continuous solid deuterium extrusion and will be integrated with a secondary section, where pellets are cut, chambered, and launched with a single-stage pneumatic accelerator into the plasma through a guide tube. This integrated pellet injection system is designed to provide 5 mm fueling pellets, injected at a rate up to 10 Hz, or 3 mm edge localizedmore » mode (ELM) triggering pellets, injected at higher rates up to 20 Hz. The pellet cutter, chamber mechanism, and the solenoid operated pneumatic valve for the accelerator are optimized to provide pellet velocities between 200-300 m/s to ensure high pellet survivability while traversing the inner wall fueling guide tubes, and outer wall ELMpacing guide tubes. This paper outlines the current twin-screwextruder design, pellet accelerator design, and the integrationrequired for both fueling and ELM pacing pellets.« less

Development of LWR Fuels with Enhanced Accident Tolerance

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

Lahoda, Edward J.; Boylan, Frank A.

2015-10-30

Significant progress was made on the technical, licensing, and business aspects of the Westinghouse Electric Company’s Enhanced Accident Tolerant Fuel (ATF) by the Westinghouse ATF team. The fuel pellet options included waterproofed U 15N and U 3Si 2 and the cladding options SiC composites and zirconium alloys with surface treatments. Technology was developed that resulted in U 3Si 2 pellets with densities of >94% being achieved at the Idaho National Laboratory (INL). The use of U 3Si 2 will represent a 15% increase in U235 loadings over those in UO₂ fuel pellets. This technology was then applied to manufacture pelletsmore » for 6 test rodlets which were inserted in the Advanced Test Reactor (ATR) in early 2015 in zirconium alloy cladding. The first of these rodlets are expected to be removed in about 2017. Key characteristics to be determined include verification of the centerline temperature calculations, thermal conductivity, fission gas release, swelling and degree of amorphization. Waterproofed UN pellets have achieved >94% density for a 32% U 3Si 2/68% UN composite pellet at Texas A&M University. This represents a U235 increase of about 31% over current UO 2 pellets. Pellets and powders of UO 2, UN, and U 3Si 2the were tested by Westinghouse and Los Alamos National Laboratory (LANL) using differential scanning calorimetry to determine what their steam and 20% oxygen corrosion temperatures were as compared to UO 2. Cold spray application of either the amorphous steel or the Ti 2AlC was successful in forming an adherent ~20 micron coating that remained after testing at 420°C in a steam autoclave. Tests at 1200°C in 100% steam on coatings for Zr alloy have not been successful, possibly due to the low density of the coatings which allowed steam transport to the base zirconium metal. Significant modeling and testing has been carried out for the SiC/SiC composite/SiC monolith structures. A structure with the monolith on the outside and composite on the inside was developed which is the current baseline structure and a SiC to SiC tube closure approach. Permeability tests and mechanical tests were developed to verify the operation of the SiC cladding. Steam autoclave (420°C), high temperature (1200°C) flowing steam tests and quench tests were carried out with minimal corrosion, mechanical or hermeticity degradation effect on the SiC cladding or end plug closure. However, in-reactor loop tests carried out in the MIT reactor indicated an unacceptable degree of corrosion, likely due to the corrosive effect of radiolysis products which attacked the SiC.« less

Sustained-release theophylline and nocturnal asthma, once-daily and unequal dosing schedules.

PubMed

Smolensky, M H; D'Alonzo, G E; Kunkel, G; Barnes, P J

1987-01-01

Many asthmatic patients experience aggravation of symptoms overnight resulting in disruption of their sleep. Sustained-release theophylline represents at this time a major bronchodilator medication which possesses a sufficient duration of activity to avert the nocturnal breathing distress of asthma. Circadian rhythm-adapted theophylline schedules consisting of unequal dosing--more or all the drug taken in the evening--have proven efficacious in clinical investigations for certain patients. Although the kinetic behavior of some formulations is affected by food, the circadian rhythm-adapted schedules represent a significant step forward toward the goal of optimizating sustained-release theophyllines for patients who experience nighttime symptoms.

Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

PubMed

Shergill, Mandip; Patel, Mina; Khan, Siraj; Bashir, Ayesha; McConville, Christopher

2016-01-30

Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70 min with 16% degradation after 120 min, while 75% degradation occurred after 120 min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of pelleting process variables on physical properties and sugar yields of ammonia fiber expansion pretreated corn stover

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

Amber N. Hoover; Jaya Shankar Tumuluru; Farzaneh Teymouri

Pelletization process variables including grind size (4, 6 mm), die speed (40, 50, 60 Hz), and preheating (none, 70 degrees C) were evaluated to understand their effect on pellet quality attributes and sugar yields of ammonia fiber expansion (AFEX) pretreated biomass. The bulk density of the pelletized AFEX corn stover was three to six times greater compared to untreated and AFEX-treated corn stover. Also the durability of the pelletized AFEX corn stover was >97.5% for all pelletization conditions studied except for preheated pellets. Die speed had no effect on enzymatic hydrolysis sugar yields of pellets. Pellets produced with preheating ormore » a larger grind size (6 mm) had similar or lower sugar yields. Pellets generated with 4 mm AFEX-treated corn stover, a 60 Hz die speed, and no preheating resulted in pellets with similar or greater density, durability, and sugar yields compared to other pelletization conditions.« less

21 CFR 520.1920 - Prochlorperazine, isopropamide sustained release capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prochlorperazine, isopropamide sustained release capsules. 520.1920 Section 520.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... dogs in which gastrointestinal disturbances are associated with emotional stress. (2)(i) Capsules...

Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

NASA Astrophysics Data System (ADS)

McCarthy, K. J.; Tamura, N.; Combs, S. K.; Panadero, N.; Ascabíbar, E.; Estrada, T.; García, R.; Hernández Sánchez, J.; López Fraguas, A.; Navarro, M.; Pastor, I.; Soleto, A.; TJ-II Team

2017-10-01

A cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun-type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection compared with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release

PubMed Central

Li, Xiao; Zhao, Yang; Wang, Kaijie; Yang, Xiaohui; Zhu, Siquan

2017-01-01

To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing β-cyclodextrin (β-CD) (pHEMA/MMA/β-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/β-CD copolymers containing different ratios of β-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing β-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering β-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, β-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/β-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery. PMID:29244868

Fungal-assisted algal flocculation: application in wastewater treatment and biofuel production.

PubMed

Muradov, Nazim; Taha, Mohamed; Miranda, Ana F; Wrede, Digby; Kadali, Krishna; Gujar, Amit; Stevenson, Trevor; Ball, Andrew S; Mouradov, Aidyn

2015-01-01

The microalgal-based industries are facing a number of important challenges that in turn affect their economic viability. Arguably the most important of these are associated with the high costs of harvesting and dewatering of the microalgal cells, the costs and sustainability of nutrient supplies and costly methods for large scale oil extraction. Existing harvesting technologies, which can account for up to 50% of the total cost, are not economically feasible because of either requiring too much energy or the addition of chemicals. Fungal-assisted flocculation is currently receiving increased attention because of its high harvesting efficiency. Moreover, some of fungal and microalgal strains are well known for their ability to treat wastewater, generating biomass which represents a renewable and sustainable feedstock for bioenergy production. We screened 33 fungal strains, isolated from compost, straws and soil for their lipid content and flocculation efficiencies against representatives of microalgae commercially used for biodiesel production, namely the heterotrophic freshwater microalgae Chlorella protothecoides and the marine microalgae Tetraselmis suecica. Lipid levels and composition were analyzed in fungal-algal pellets grown on media containing alternative carbon, nitrogen and phosphorus sources from wheat straw and swine wastewater, respectively. The biomass of fungal-algal pellets grown on swine wastewater was used as feedstock for the production of value-added chemicals, biogas, bio-solids and liquid petrochemicals through pyrolysis. Co-cultivation of microalgae and filamentous fungus increased total biomass production, lipid yield and wastewater bioremediation efficiency. Fungal-assisted microalgal flocculation shows significant potential for solving the major challenges facing the commercialization of microalgal biotechnology, namely (i) the efficient and cost-effective harvesting of freshwater and seawater algal strains; (ii) enhancement of total oil production and optimization of its composition; (iii) nutrient supply through recovering of the primary nutrients, nitrogen and phosphates and microelements from wastewater. The biomass generated was thermochemically converted into biogas, bio-solids and a range of liquid petrochemicals including straight-chain C12 to C21 alkanes which can be directly used as a glycerine-free component of biodiesel. Pyrolysis represents an efficient alternative strategy for biofuel production from species with tough cell walls such as fungi and fungal-algal pellets.

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.

21 CFR 520.1197 - Ivermectin sustained-release bolus.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin sustained-release bolus. 520.1197 Section 520.1197 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1197 Ivermectin...

Design and performance of a punch mechanism based pellet injector for alternative injection in the large helical device

NASA Astrophysics Data System (ADS)

Mishra, J. S.; Sakamoto, R.; Motojima, G.; Matsuyama, A.; Yamada, H.

2011-02-01

A low speed single barrel pellet injector, using a mechanical punch device has been developed for alternative injection in the large helical device. A pellet is injected by the combined operation of a mechanical punch and a pneumatic propellant system. The pellet shape is cylindrical, 3 mm in diameter and 3 mm in length. Using this technique the speed of the pellet can be controlled flexibly in the range of 100-450 m/s, and a higher speed can be feasible for a higher gas pressure. The injector is equipped with a guide tube selector to direct the pellet to different injection locations. Pellets are exposed to several curved parts with the curvature radii Rc = 0.8 and 0.3 m when they are transferred in guided tubes to the respective injection locations. Pellet speed variation with pressure at different pellet formation temperatures has been observed. Pellet intactness tests through these guide tubes show a variation in the intact speed limit over a range of pellet formation temperatures from 6.5 to 9.8 K. Pellet speed reduction of less than 6% has been observed after the pellet moves through the curved guide tubes.

Fabrication of micro-cell UO2-Mo pellet with enhanced thermal conductivity

NASA Astrophysics Data System (ADS)

Kim, Dong-Joo; Rhee, Young Woo; Kim, Jong Hun; Kim, Keon Sik; Oh, Jang Soo; Yang, Jae Ho; Koo, Yang-Hyun; Song, Kun-Woo

2015-07-01

As one of accident tolerant fuel pellets which should have features of good thermal conductivity and high fission product retention, a micro-cell UO2-Mo pellet has been studied in the aspect of fabrication and thermal property. It was intended to develop the compatible process with conventional UO2 pellet fabrication process. The effects of processing parameters such as the size and density of UO2 granule and the size of Mo powder have been studied to produce sound and dense pellet with completely connected uniform Mo cell-walls. The micro-cell UO2-Mo pellet consists of many Mo micro-cells and UO2 in them. The thermal conductivity of the micro-cell UO2-Mo pellet was measured and compared to those of the UO2 pellet and the UO2-Mo pellet with dispersed form of Mo particles. The thermal conductivity of the micro-cell UO2-Mo pellet was much enhanced and was found to be influenced by the Mo volumetric fraction and pellet integrity. A continuous Mo micro-cell works as a heat conducting channel in the pellet, greatly enhancing the thermal conductivity of the micro cell UO2-Mo pellet.

Statistical analysis and modeling of pelletized cultivation of Mucor circinelloides for microbial lipid accumulation.

PubMed

Xia, Chunjie; Wei, Wei; Hu, Bo

2014-04-01

Microbial oil accumulation via oleaginous fungi has some potential benefits because filamentous fungi can form pellets during cell growth and these pellets are easier to harvest from the culture broth than individual cells. This research studied the effect of various culture conditions on the pelletized cell growth of Mucor circinelloides and its lipid accumulation. The results showed that cell pelletization was positively correlated to biomass accumulation; however, pellet size was negatively correlated to the oil content of the fungal biomass, possibly due to the mass transfer barriers generated by the pellet structure. How to control the size of the pellet is the key to the success of the pelletized microbial oil accumulation process.

[Studies on preparation of sustained-release Shuxiong formulation, a traditional Chinese medicine compound recipe, using time-controlled release techniques].

PubMed

Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui

2006-09-01

To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.

"Luck's always to blame": silent wounds of a penetrating gunshot trauma sustained 20 years ago.

PubMed

Tomos, Ioannis; Manali, Effrosyni D; Argentos, Stylianos; Raptakis, Thomas; Papiris, Spyros A

2015-01-01

Gunshot tracheal injuries represent life-threatening events and usually necessitate emergent surgical intervention. We report a case of an exceptional finding of a patient with retained ballistic fragments in the soft tissues of the thorax, proximal to the right subclavian artery and the trachea, carrying silently his wounds for two decades without any medical or surgical intervention. The bullet pellet on the upper part of the trachea seen accidentally in the chest computed tomography, was also found during bronchoscopy. In short "luck's always to blame".

Sustained Release Drug Delivery Applications of Polyurethanes.

PubMed

Lowinger, Michael B; Barrett, Stephanie E; Zhang, Feng; Williams, Robert O

2018-05-09

Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described.

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100.

PubMed

El Maghraby, Gamal Mohamed; Elzayat, Ehab Mostafa; Alanazi, Fars Kaed

2014-03-01

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels.

Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology.

PubMed

McConville, Christopher; Major, Ian; Devlin, Brid; Brimer, Andrew

2016-07-01

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control. Copyright © 2016 Elsevier B.V. All rights reserved.

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

PubMed

Brouillet, F; Bataille, B; Cartilier, L

2008-05-22

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

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

PubMed

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

2017-08-01

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

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release.

PubMed

Chen, Muwan; Le, Dang Q S; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

2012-01-01

Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug.

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

PubMed Central

Chen, Muwan; Le, Dang QS; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

2012-01-01

Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug. PMID:22904634

Preparation and evaluation of sustained drug release from pluronic polyol rectal suppositories.

PubMed

Anderson, D; Amomo, M M

2001-01-01

Suppository dosage forms offer several advantages in drug delivery and can be compounded in a pharmacy setting for the needs of the individual patient. In this study, we have examined the use of Pluronic polyols in the development of sustained-release rectal suppository formulations. Solid and liquid Pluronic poyols (Pluronic L61, F68, L101, and F108) were combined in a weight ratio ranging from 80:20 (solid to liquid) to 70:30 to prepare the bases. The release behavior of a model drug, riboflavin, from the suppositories wee evaluated by means of the United Stated Pharmacopeia Basket Dissolution Method. When compared with the control Polybase suppository, which released 50% of the drug (t50) in about 7.23 minutes, Pluronic F68/L61 suppositories at an 80:20 weight ratio exhibited a t50 of 86.5 minutes (1.44 hours). Riboflavin release from suppositories made with Pluronic F108/L101 was even further delayed. The t50 of riboflavin from Pluronic F108/L101 suppositories at an 80:20 weight ratio, for instance, was 274.4 minutes (4.6 hours). The results of this study show that by choosing specific combinations of Pluronic polyols and weight ratios, compounding pharmacists can prepare sustained-release suppository formulations that can deliver drugs within minutes to hours. This flexibility of compounding sustained-release suppositories is beneficial, especially for the management of chronic pain in cancer patients.

Method to Produce Durable Pellets at Lower Energy Consumption Using High Moisture Corn Stover and a Corn Starch Binder in a Flat Die Pellet Mill

PubMed Central

Tumuluru, Jaya Shankar; Conner, Craig C.; Hoover, Amber N.

2016-01-01

A major challenge in the production of pellets is the high cost associated with drying biomass from 30 to 10% (w.b.) moisture content. At Idaho National Laboratory, a high-moisture pelleting process was developed to reduce the drying cost. In this process the biomass pellets are produced at higher feedstock moisture contents than conventional methods, and the high moisture pellets produced are further dried in energy efficient dryers. This process helps to reduce the feedstock moisture content by about 5-10% during pelleting, which is mainly due to frictional heat developed in the die. The objective of this research was to explore how binder addition influences the pellet quality and energy consumption of the high-moisture pelleting process in a flat die pellet mill. In the present study, raw corn stover was pelleted at moistures of 33, 36, and 39% (w.b.) by addition of 0, 2, and 4% pure corn starch. The partially dried pellets produced were further dried in a laboratory oven at 70 °C for 3-4 hr to lower the pellet moisture to less than 9% (w.b.). The high moisture and dried pellets were evaluated for their physical properties, such as bulk density and durability. The results indicated that increasing the binder percentage to 4% improved pellet durability and reduced the specific energy consumption by 20-40% compared to pellets with no binder. At higher binder addition (4%), the reduction in feedstock moisture during pelleting was <4%, whereas the reduction was about 7-8% without the binder. With 4% binder and 33% (w.b.) feedstock moisture content, the bulk density and durability values observed of the dried pellets were >510 kg/m3 and >98%, respectively, and the percent fine particles generated was reduced to <3%. PMID:27340875

Method to Produce Durable Pellets at Lower Energy Consumption Using High Moisture Corn Stover and a Corn Starch Binder in a Flat Die Pellet Mill.

PubMed

Tumuluru, Jaya Shankar; Conner, Craig C; Hoover, Amber N

2016-06-15

A major challenge in the production of pellets is the high cost associated with drying biomass from 30 to 10% (w.b.) moisture content. At Idaho National Laboratory, a high-moisture pelleting process was developed to reduce the drying cost. In this process the biomass pellets are produced at higher feedstock moisture contents than conventional methods, and the high moisture pellets produced are further dried in energy efficient dryers. This process helps to reduce the feedstock moisture content by about 5-10% during pelleting, which is mainly due to frictional heat developed in the die. The objective of this research was to explore how binder addition influences the pellet quality and energy consumption of the high-moisture pelleting process in a flat die pellet mill. In the present study, raw corn stover was pelleted at moistures of 33, 36, and 39% (w.b.) by addition of 0, 2, and 4% pure corn starch. The partially dried pellets produced were further dried in a laboratory oven at 70 °C for 3-4 hr to lower the pellet moisture to less than 9% (w.b.). The high moisture and dried pellets were evaluated for their physical properties, such as bulk density and durability. The results indicated that increasing the binder percentage to 4% improved pellet durability and reduced the specific energy consumption by 20-40% compared to pellets with no binder. At higher binder addition (4%), the reduction in feedstock moisture during pelleting was <4%, whereas the reduction was about 7-8% without the binder. With 4% binder and 33% (w.b.) feedstock moisture content, the bulk density and durability values observed of the dried pellets were >510 kg/m(3) and >98%, respectively, and the percent fine particles generated was reduced to <3%.

Characterization of Nano Bamboo Charcoal Drug Delivery System for Eucommia ulmoides Extract and Its Anticancer Effect In vitro.

PubMed

Zeng, Zhaoyan; Li, Xiangzhou; Zhang, Sheng; Huang, Dan

2017-01-01

Nano bamboo charcoal is being widely used as sustained release carrier for chemicals for its high specific surface area, sound biocompatibility, and nontoxicity; however, there have been no reports on nano bamboo charcoal as sustained release carrier for traditional Chinese medicine (TCM). To study the effect of nano bamboo charcoal in absorbing and sustained releasing Eucommia ulmoides extract (EUE) and to verify the in vitro anticancer effect of the sustained release liquid, so as to provide a theoretical basis for the development and utilization of nano bamboo charcoal as TCM sustained-release preparation. The adsorption capacity for the nano bamboo charcoal on EUE was measured by Langmuir model, and the release experiment was carried out under intestinal fluid condition. Characteristic changes for the nano bamboo charcoal nano-drug delivery system with and without adsorption of E. ulmoides were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and specific surface area. In addition, the anticancer effect from this novel bamboo charcoal E. ulmoides delivery system was evaluated against a human colon cancer cell line (HCT116). It was found that nano bamboo charcoal exhibits good adsorption capacity (up to 462.96 mg/g at 37°C). The cumulative release rate for EUE from this nano bamboo charcoal delivery system was 70.67%, and specific surface area for the nano bamboo charcoal decreased from 820.32 m 2 /g to 443.80 m 2 /g after EUE was loaded. An in vitro anticancer study showed that the inhibition rate for E. ulmoides against HCT116 cancer cells was 23.07%, for this novel bamboo charcoal nano-drug delivery system. This study provides a novel strategy for the delivery of traditional Chinese medicine using bamboo charcoal nano-drug delivery system. The adsorption equilibrium was reached after 30 min of ultrasonic treatmentThe saturated adsorption capacity of Eucommia ulmoides extract by nano bamboo charcoal under ultrosonic condition was 462. 96 mg/gThe cumulative release rate of E. ulmoides extract from the nano bamboo charcoal delivery system in artificial intestinal juice was 70.67%The inhibition ratio of HCT116 cancer cells by sustained release liquid was 23.07%. Abbreviation used: EUE: Eucommia ulmoides extract.

Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Tan, Nguan Soon; Loo, Say Chye Joachim

2017-10-06

Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique. Hollow microparticles were formed through the addition of an osmolyte into the fabrication process. The benefits of hollow over solid microparticles were found to be higher encapsulation efficiency and a more rapid drug release rate. Further modification of the hollow microparticles was accomplished through the introduction of methyl-β-cyclodextrin. With this, a higher encapsulation efficiency of both drugs and an enhanced cumulative release were achieved. Spheroid study further demonstrated that the controlled release of the drugs from the methyl-β-cyclodextrin -loaded hollow microparticles exhibited enhanced tumor regressions of MCF-7 tumor spheroids. Such hollow dual-drug-loaded hollow microparticles with sustained releasing capabilities may have a potential for future applications in cancer therapy.

Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.

PubMed

Qi, Na; Cai, Cuifang; Zhang, Wei; Niu, Yantao; Yang, Jingyu; Wang, Lihui; Tian, Bin; Liu, Xiaona; Lin, Xia; Zhang, Yu; Zhang, Yan; He, Haibing; Chen, Kang; Tang, Xing

2014-09-10

This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

DOE PAGES

McCarthy, K. J.; Tamura, N.; Combs, S. K.; ...

2018-01-05

Here, a cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun–type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection comparedmore » with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.« less

Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

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

McCarthy, K. J.; Tamura, N.; Combs, S. K.

Here, a cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun–type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection comparedmore » with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.« less

A Novel Technique that Enables Efficient Conduct of Simultaneous Isomerization and Fermentation (SIF) of Xylose

NASA Astrophysics Data System (ADS)

Rao, Kripa; Chelikani, Silpa; Relue, Patricia; Varanasi, Sasidhar

Of the sugars recovered from lignocellulose, D-glucose can be readily converted into ethanol by baker's or brewer's yeast (Saccharomyces cerevisiae). However, xylose that is obtained by the hydrolysis of the hemicellulosic portion is not fermentable by the same species of yeasts. Xylose fermentation by native yeasts can be achieved via isomerization of xylose to its ketose isomer, xylulose. Isomerization with exogenous xylose isomerase (XI) occurs optimally at a pH of 7-8, whereas subsequent fermentation of xylulose to ethanol occurs at a pH of 4-5. We present a novel scheme for efficient isomerization of xylose to xylulose at conditions suitable for the fermentation by using an immobilized enzyme system capable of sustaining two different pH microenvironments in a single vessel. The proof-of-concept of the two-enzyme pellet is presented, showing conversion of xylose to xylulose even when the immobilized enzyme pellets are suspended in a bulk solution whose pH is sub-optimal for XI activity. The co-immobilized enzyme pellets may prove extremely valuable in effectively conducting "simultaneous isomerization and fermentation" (SIF) of xylose. To help further shift the equilibrium in favor of xylulose formation, sodium tetraborate (borax) was added to the isomerization solution. Binding of tetrahydroxyborate ions to xylulose effectively reduces the concentration of xylulose and leads to increased xylose isomerization. The formation of tetrahydroxyborate ions and the enhancement in xylulose production resulting from the complexation was studied at two different bulk pH values. The addition of 0.05 M borax to the isomerization solution containing our co-immobilized enzyme pellets resulted in xylose to xylulose conversion as high as 86% under pH conditions that are suboptimal for XI activity. These initial findings, which can be optimized for industrial conditions, have significant potential for increasing the yield of ethanol from xylose in an SIF approach.

Lignite pellets and methods of agglomerating or pelletizing

DOEpatents

Baker, Albert F.; Blaustein, Eric W.; Deurbrouck, Albert W.; Garvin, John P.; McKeever, Robert E.

1981-01-01

The specification discloses lignite pellets which are relatively hard, dust resistant, of generally uniform size and free from spontaneous ignition and general degradation. Also disclosed are methods for making such pellets which involve crushing as mined lignite, mixing said lignite with a binder such as asphalt, forming the lignite binder mixture into pellets, and drying the pellets.

Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

NASA Technical Reports Server (NTRS)

McAllister, T. N.; Frangos, J. A.

1999-01-01

Fluid flow has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load-induced bone remodeling. The objective of this study was to investigate the characteristics of flow-activated pathways. Previously we reported that fluid flow stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts. Here we demonstrate that flow-induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of flow stimulated a burst in NO production (8.2 nmol/mg of protein/h), while steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h). Both G-protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G-proteins stimulated dose-dependent NO release in static cultures of both calvarial osteoblasts and UMR-106 osteoblast-like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G-protein and calcium-dependent phase sensitive to flow transients, and a G-protein and calcium-independent pathway stimulated by sustained flow.

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.

Evaluation of water uptake and mechanical properties of blended polymer films for preparing gas-generated multiple-unit floating drug delivery systems.

PubMed

Chen, Ying-Chen; Lee, Lin-Wen; Ho, Hsiu-O; Sha, Chen; Sheu, Ming-Thau

2012-10-01

Among various strategies of gastroretentive drug delivery systems (DDSs) developed to prolong the gastric residence time and to increase the overall bioavailability, effervescent multiple-unit floating DDSs (muFDDSs) were studied here. These systems consist of drug (losartan)- and effervescent (sodium bicarbonate)-containing pellets coated with a blended polymeric membrane, which was a mixture of gastrointestinal tract (GIT)-soluble and GIT-insoluble polymers. The addition of GIT-soluble polymers, such as hydroxypropyl methylcellulose, polyethylene glycol (PEG) 6000, PEG 600, and Kollicoat® IR, greatly increased the water uptake ability of the GIT-insoluble polymers (Eudragit® NE, RS, and RL; Surelease®; and Kollicoat® SR) and caused them to immediately initiate the effervescent reaction and float, but the hydrated films should also be impermeable to the generated CO(2) to maintain floatation and sufficiently flexible to withstand the pressure of carbon dioxide to avoid rupturing. The study demonstrated that the water uptake ability and mechanical properties could be applied as screening tools during the development of effervescent muFDDSs. The optimized system of SRT(5)P600(5) (i.e., a mixture of 5% Kollicoat® SR and 5% PEG 600) with a 20% coating level began to completely float within 15 min and maintained its buoyancy over a period of 12 h with a sustained-release effect. Copyright © 2012 Wiley Periodicals, Inc.

Potential applications for halloysite nanotubes based drug delivery systems

NASA Astrophysics Data System (ADS)

Sun, Lin

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate could be released in a sustained manner; (2) cytotoxicity test confirmed the biocompatibility of HNTs and methotrexate coated HNTs; (3) proliferation test confirmed the growth inhibition of released methotrexate on osteosarcoma cells; and (4) nylon-6 could prolong the sustained release of methotrexate from polyelectrolytes coated HNTs. Another application comes from the prevention of surgical site infection. It is a common complication in surgery, which may prolong hospital stay, increase mortality rate, and cause additional financial burden for patients. By directly releasing antibiotics at the surgical site, it is supposed to enhance the drug efficacy and improve the treatment outcome. Therefore, the same HNTs based system was tested with E. coli in vitro to show the potential of delivering antibiotics to enhance the prevention of surgical site infection. Nitrofurantoin was incorporated within HNTs using the layer-by-layer coating technique, and the drug coated HNTs were filled into nylon-6 again. Results showed that (1) nitrofurantoin could be incorporated with this HNTs based drug delivery system, and released in a sustained manner; (2) nylon-6 could prolong the sustained release of nitrofurantoin from polyelectrolytes coated HNTs; and (3) released nitrofurantoin could severely inhibit E. coil growth. Therefore, a tunable drug delivery system based on HNTs was developed, and a great potential of medical application in drug delivery was shown.

Effects of thermal treatment on energy density and hardness of torrefied wood pellets

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

Peng, Jianghong; Wang, Jingsong; Bi, Xiaotao T.

Here, three types of wood pellets samples, including two types of commercial pellets and one type of lab-made control pellets were torrefied in a fixed bed unit to study the effect of thermal pretreatment on the quality of wood pellets. The quality of wood pellets was mainly characterized by the pellet density, bulk density, higher heating value, Meyer hardness, saturated moisture uptake, volumetric energy density, and energy yield. Results showed that torrefaction significantly decreased the pellet density, hardness, volumetric energy density, and energy yield. The higher heating value increased and the saturated moisture content decreased after torrefaction. In view ofmore » the lower density, lower hardness, lower volumetric energy density, and energy yield of torrefied pellets, it is recommended that biomass should be torrefied and then compressed to make strong pellets of high hydrophobicity and volumetric energy density.« less

Effects of thermal treatment on energy density and hardness of torrefied wood pellets

DOE PAGES

Peng, Jianghong; Wang, Jingsong; Bi, Xiaotao T.; ...

2014-09-27

Here, three types of wood pellets samples, including two types of commercial pellets and one type of lab-made control pellets were torrefied in a fixed bed unit to study the effect of thermal pretreatment on the quality of wood pellets. The quality of wood pellets was mainly characterized by the pellet density, bulk density, higher heating value, Meyer hardness, saturated moisture uptake, volumetric energy density, and energy yield. Results showed that torrefaction significantly decreased the pellet density, hardness, volumetric energy density, and energy yield. The higher heating value increased and the saturated moisture content decreased after torrefaction. In view ofmore » the lower density, lower hardness, lower volumetric energy density, and energy yield of torrefied pellets, it is recommended that biomass should be torrefied and then compressed to make strong pellets of high hydrophobicity and volumetric energy density.« less

Spray-dried nanofibrillar cellulose microparticles for sustained drug release.

PubMed

Kolakovic, Ruzica; Laaksonen, Timo; Peltonen, Leena; Laukkanen, Antti; Hirvonen, Jouni

2012-07-01

Nanofibrillar cellulose (also referred to as cellulose nanofibers, nanocellulose, microfibrillated or nanofibrillated cellulose) has gained a lot of attention in recent years in different research areas including biomedical applications. In this study we have evaluated the applicability of nanofibrillar cellulose (NFC) as a material for the formation of matrix systems for sustained drug delivery. For that purpose, drug loaded NFC microparticles were produced by a spray drying method. The microparticles were characterized in terms of size and morphology, total drug loading, and physical state of the encapsulated drug. Drug release from the microparticles was assessed by dissolution tests, and suitable mathematical models were used to explain the drug releasing kinetics. The particles had spherical shapes with diameters of around 5 μm; the encapsulated drug was mainly in amorphous form. The controlled drug release was achieved. The drug releasing curves were fitted to a mathematical model describing the drug releasing kinetics from a spherical matrix. Different drugs had different release kinetics, which was a consequence of several factors, including different solubilities of the drugs in the chosen medium and different affinities of the drugs to the NFC. It can be concluded that NFC microparticles can sustain drug release by forming a tight fiber network and thus limit drug diffusion from the system. Copyright © 2012 Elsevier B.V. All rights reserved.

Characterization and optimization of GMO-based gels with long term release for intraarticular administration.

PubMed

Réeff, J; Gaignaux, A; Goole, J; Siepmann, J; Siepmann, F; Jerome, C; Thomassin, J M; De Vriese, C; Amighi, K

2013-07-15

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release. Copyright © 2013. Published by Elsevier B.V.

Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Upadhye, Sampada B; Vladyka, Ronald S; Repka, Michael A

2015-12-30

The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder. Copyright © 2015 Elsevier B.V. All rights reserved.

A pillar[5]arene based gel from a low-molecular-weight gelator for sustained dye release in water.

PubMed

Yao, Yong; Sun, Yan; Yu, Huaxu; Chen, Wenrui; Dai, Hong; Shi, Yujun

2017-12-12

A soft gel based on pillar[5]arene was successfully prepared using a carbazone reaction. Furthermore, dyes such as TPP or TPPE can be incorporated into this gel and were observed to be released in a sustained way in water due to solvent exchange.

Bioequivalence of progesterone sustained release suppository in rabbits.

PubMed

Long, Lihong; Huang, Qun; Wu, Minghui; Hou, Shuxian; Dai, Zongshun

2005-01-01

To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross-over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository (tested formulation, T) and progesterone suppository (reference formulation, R) was administered; a multiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were: for single and multiple doses, Cmax was 48.8 +/- 11.8 ng/mL and 43.5 +/- 9.4 ng/mL, Tmax was 0.5 +/- 0.3 h and 0.4 +/- 0.3 h, AUC(0-24 h) was 362.4 +/- 143 ng x h x mL(-1) and 310.6 +/- 70.3 ng x h x mL(-1), respectively. The relative bioavailability of T to R were (104.2 +/- 13.4)% and (111.4 +/- 19.1)%, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.

The Asian Wood Pellet Markets

Treesearch

Joseph A. Roos; Allen Brackley

2012-01-01

This study examines the three major wood pellet markets in Asia: China, Japan, and South Korea. In contrast to the United States, where most wood pellets are used for residential heating with pellet stoves, a majority of the wood pellets in Asia are used for co-firing at coal-fired power plants. Our analysis indicated that Japan is the largest importer of wood pellets...

Production and characterization of pellets using Avicel CL611 as spheronization aid.

PubMed

Puah, Sin Yee; Yap, Hsiu Ni; Chaw, Cheng Shu

2014-03-01

The study looked into the feasibility of producing pellet using Avicel CL611 as spheronization aid by the extrusion/spheronization technique. Pellets were formulated to contain either 20% or 40% Avicel CL611 and lactose monohydrate as the other sole ingredient. Water is used as liquid binder. Quality of pellets and extrudates were analyzed for size distribution, shape, surface tensile strength and disintegration profile. More water was needed when higher Avicel CL611 fraction was used during the production of pellets. The pellets of larger size were obtained by increasing the water content. Pellets with aspect ratios of ∼1.1 were produced with high spheronization speed at short residence time. Higher tensile strength was achieved when increasing the water content and the fraction of Avicel CL611 during pellet production. These pellets also took longer time to disintegrate, nonetheless all the pellets disintegrated within 15 min. A positive linear relationship was obtained between the tensile strength and time for pellets to disintegrate. Strong but round pellets that disintegrate rapidly could be produced with Avicel CL611 as spheronization aid using moderately soluble compounds such as lactose.

Influence of the interpellet space to the Instant Release Fraction determination of a commercial UO2 Boiling Water Reactor Spent Nuclear Fuel

NASA Astrophysics Data System (ADS)

Martínez-Torrents, A.; Serrano-Purroy, D.; Casas, I.; De Pablo, J.

2018-02-01

The contact of the coolant with the fuel pin during irradiation produces a gradient of temperature in the fuel pellet that segregates the radionuclides (RN) depending on its volatility and reactivity. This segregation determines the Instant Release Fraction (IRF), an important source of radiological risk in the performance assessment (PA) of a Deep Geologic Repository (DGR). RN segregation was studied radially in previous papers. In the present work, it was studied axially, taking into special consideration the cutting position of the solid sample to be studied. Iodine and caesium were the RN with the highest release, while the contribution of rubidium, strontium, molybdenum and technetium to the IRF depended on their chemical state. The interpellet presence (known also as dishing) effect was clearly observed for caesium, increasing its release by one order of magnitude. According to these results, one of the major contributions to the IRF comes from the RN trapped in the dishing and has to be considered in the sampling and data interpretation that will be performed for the PA of the DGR.

Fractal Model of Fission Product Release in Nuclear Fuel

NASA Astrophysics Data System (ADS)

Stankunas, Gediminas

2012-09-01

A model of fission gas migration in nuclear fuel pellet is proposed. Diffusion process of fission gas in granular structure of nuclear fuel with presence of inter-granular bubbles in the fuel matrix is simulated by fractional diffusion model. The Grunwald-Letnikov derivative parameter characterizes the influence of porous fuel matrix on the diffusion process of fission gas. A finite-difference method for solving fractional diffusion equations is considered. Numerical solution of diffusion equation shows correlation of fission gas release and Grunwald-Letnikov derivative parameter. Calculated profile of fission gas concentration distribution is similar to that obtained in the experimental studies. Diffusion of fission gas is modeled for real RBMK-1500 fuel operation conditions. A functional dependence of Grunwald-Letnikov derivative parameter with fuel burn-up is established.

Probing RFP Density Limits and the Interaction of Pellet Fueling and NBI Heating on MST

NASA Astrophysics Data System (ADS)

Caspary, K. J.; Chapman, B. E.; Anderson, J. K.; Limbach, S. T.; Oliva, S. P.; Sarff, J. S.; Waksman, J.; Combs, S. K.; Foust, C. R.

2013-10-01

Pellet fueling on MST has previously achieved Greenwald fractions of up to 1.5 in 200 kA improved confinement discharges. Additionally, pellet fueling to densities above the Greenwald limit in 200 kA standard discharges resulted in early termination of the plasma, but pellet size was insufficient to exceed the limit for higher current discharges. To this end, the pellet injector on MST has been upgraded to increase the maximum fueling capability by increasing the size of the pellet guide tubes, which constrain the lateral motion of the pellet in flight, to accommodate pellets of up to 4.0 mm in diameter. These 4.0 mm pellets are capable of triggering density limit terminations for MST's peak current of 600 kA. An unexpected improvement in the pellet speed and mass control was also observed compared to the smaller diameter pellets. Exploring the effect of increased density on NBI particle and heat deposition shows that for MST's 1 MW tangential NBI, core deposition of 25 keV neutrals is optimized for densities of 2-3 × 1019 m-3. This is key for beta limit studies in pellet fueled discharges with improved confinement where maximum NBI heating is desired. An observed toroidal deflection of pellets injected into NBI heated discharges is consistent with asymmetric ablation due to the fast ion population. In 200 kA improved confinement plasmas with NBI heating, pellet fueling has achieved a Greenwald fraction of 2.0. Work supported by US DoE.

ELM mitigation with pellet ELM triggering and implications for PFCs and plasma performance in ITER

DOE PAGES

Baylor, Larry R.; Lang, P. T.; Allen, Steve L.; ...

2014-10-05

The triggering of rapid small edge localized modes (ELMs) by high frequency pellet injection has been proposed as a method to prevent large naturally occurring ELMs that can erode the ITER plasma facing components. Deuterium pellet injection has been used to successfully demonstrate the on-demand triggering of edge localized modes (ELMs) at much higher rates and with much smaller intensity than natural ELMs. The proposed hypothesis for the triggering mechanism of ELMs by pellets is the local pressure perturbation resulting from reheating of the pellet cloud that can exceed the local high-n ballooning mode threshold where the pellet is injected.more » Nonlinear MHD simulations of the pellet ELM triggering show destabilization of high-n ballooning modes by such a local pressure perturbation. A review of the recent pellet ELM triggering results from ASDEX Upgrade (AUG), DIII-D, and JET reveals that a number of uncertainties about this ELM mitigation technique still remain. These include the heat flux impact pattern on the divertor and wall from pellet triggered and natural ELMs, the necessary pellet size and injection location to reliably trigger ELMs, and the level of fueling to be expected from ELM triggering pellets and synergy with larger fueling pellets. The implications of these issues for pellet ELM mitigation in ITER and its impact on the PFCs are presented along with the design features of the pellet injection system for ITER.« less

ELM mitigation with pellet ELM triggering and implications for PFCs and plasma performance in ITER

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

Baylor, Larry R.; Lang, P.; Allen, S. L.

2015-08-01

The triggering of rapid small edge localized modes (ELMs) by high frequency pellet injection has been proposed as a method to prevent large naturally occurring ELMs that can erode the ITER plasma facing components (PFCs). Deuterium pellet injection has been used to successfully demonstrate the on-demand triggering of edge localized modes (ELMs) at much higher rates and with much smaller intensity than natural ELMs. The proposed hypothesis for the triggering mechanism of ELMs by pellets is the local pressure perturbation resulting from reheating of the pellet cloud that can exceed the local high-n ballooning mode threshold where the pellet ismore » injected. Nonlinear MHD simulations of the pellet ELM triggering show destabilization of high-n ballooning modes by such a local pressure perturbation.A review of the recent pellet ELM triggering results from ASDEX Upgrade (AUG), DIII-D, and JET reveals that a number of uncertainties about this ELM mitigation technique still remain. These include the heat flux impact pattern on the divertor and wall from pellet triggered and natural ELMs, the necessary pellet size and injection location to reliably trigger ELMs, and the level of fueling to be expected from ELM triggering pellets and synergy with larger fueling pellets. The implications of these issues for pellet ELM mitigation in ITER and its impact on the PFCs are presented along with the design features of the pellet injection system for ITER.« less

Production of LEU Fully Ceramic Microencapsulated Fuel for Irradiation Testing

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

Terrani, Kurt A; Kiggans Jr, James O; McMurray, Jake W

2016-01-01

Fully Ceramic Microencapsulated (FCM) fuel consists of tristructural isotropic (TRISO) fuel particles embedded inside a SiC matrix. This fuel inherently possesses multiple barriers to fission product release, namely the various coating layers in the TRISO fuel particle as well as the dense SiC matrix that hosts these particles. This coupled with the excellent oxidation resistance of the SiC matrix and the SiC coating layer in the TRISO particle designate this concept as an accident tolerant fuel (ATF). The FCM fuel takes advantage of uranium nitride kernels instead of oxide or oxide-carbide kernels used in high temperature gas reactors to enhancemore » heavy metal loading in the highly moderated LWRs. Production of these kernels with appropriate density, coating layer development to produce UN TRISO particles, and consolidation of these particles inside a SiC matrix have been codified thanks to significant R&D supported by US DOE Fuel Cycle R&D program. Also, surrogate FCM pellets (pellets with zirconia instead of uranium-bearing kernels) have been neutron irradiated and the stability of the matrix and coating layer under LWR irradiation conditions have been established. Currently the focus is on production of LEU (7.3% U-235 enrichment) FCM pellets to be utilized for irradiation testing. The irradiation is planned at INL s Advanced Test Reactor (ATR). This is a critical step in development of this fuel concept to establish the ability of this fuel to retain fission products under prototypical irradiation conditions.« less

Production of Dissolved Organic Matter During Doliolid Feeding

NASA Astrophysics Data System (ADS)

Castellane, N. J.; Paffenhofer, G. A.; Stubbins, A.

2016-02-01

The biological carbon pump (BCP) draws carbon dioxide out of the atmosphere and buries it at the seafloor. The efficiency of the BCP is determined in part by the sinking rates of particulate organic carbon (POC) from ocean surface waters. Zooplankton can package POC into fecal pellets with higher sinking rates than their food source (e.g. phytoplankton), increasing the efficiency of the BCP. However, dissolved organic carbon (DOC) is also produced as zooplankton ingest and egest food, reducing the efficiency of BCP. The pelagic tunicate Dolioletta gegenbauri (doliolid) is a gelatinous zooplankton found at high concentrations in shelf waters, including our study site: the South Atlantic Bight. Doliolids are efficient grazers capable of stripping large quantities of phytoplankton from the water column. To determine the balance between pellet formation and DOC production during feeding, doliolids (6-7 mm gonozooids) were placed in natural seawater amended with a live phytoplankton food source and incubated on a plankton wheel. Dissolved organic matter (DOM) released directly to the water as well as the water soluble fraction of pellet organic matter were quantified and optically characterized. Colored dissolved organic matter (CDOM) absorbance and fluorescence spectra revealed that doliolid feeding produces DOM with optical properties that are commonly indicative of newly produced, highly biolabile DOM of microbial origin. Based upon these optical characteristics, doliolid-produced DOM is expected to be highly bio-labile in the environment and therefore rapidly degraded by surface ocean microbes shunting phytoplankton-derived organic carbon out of the BCP and back to dissolved inorganic carbon.

Preparation and pharmaceutical evaluation of new sustained-release capsule including starch-sponge matrix (SSM).

PubMed

Shibata, Nobuhito; Nishumura, Asako; Naruhashi, Kazumasa; Nakao, Yurie; Miura, Rieko

2010-05-01

The focus of current study was to demonstrate a new sustained-release capsule including starch-sponge matrix (SSM) and to investigate how the pharmaceutical properties of SSM affect the drug release or its pharmacokinetic properties. Three representative drugs (uranine [UN], indomethacin [IMC] and nifedipine [NFP]) with different physicochemical properties (LogP(ow): 0.10, 1.18 and 3.23, respectively) were selected as model drugs. Model drug was dispersioned in pastelike cornstarch (starch glue) after heating 2.0-3.0% cornstarch suspension with electromagnetic wave at 2450 MHz (700 W) for l min. Then the drug mixture was encapsulated into a gratin capsule by a syringe, and the SSM including drug was prepared by means of a freeze-dried method. Essentially, drug-free SSM has a porous and netlike structure, and the distribution aspect of model drugs in the SSM depends on physicochemical properties between cornstarch glue and drugs. UN with much lower lipophilicity exists in continues phase of SSM, and IMC or NFP with a moderate or a higher lipophilicity exist in continues phase or porous space of the SSM. In the in vitro dissolution study, the release rate of drug from the SSM was mainly dependent on the lipophilicities of drugs, showing a rank order of the release rate of UN>IMC>NFP. In addition, the in vitro release rate for each drug was well regulated by changing the initial concentration of cornstarch suspension. In vivo absorption studies after intraduodenal administration of SSM capsule including model drug revealed that the sustained-release effects also could be regulated by the initial concentration of starch suspension. Moreover, the sustained-release effect of SSM capsule was enhanced with an increase in the lipophilicity of drug, and local-residential and mucoadhesive properties of SSM in the intestine provided stable supply of drugs from the SSM. The SSM capsule we developed here shows promising results as an oral drug delivery system for sustained-release regulation or target specificity. 2009 Elsevier Masson SAS. All rights reserved.

Bupropion

MedlinePlus

... as a tablet and a sustained-release or extended-release (long-acting) tablet to take by mouth. ... with doses at least 8 hours apart. The extended-release tablet (Aplenzin, Wellbutrin XL) is usually taken ...

Controlling Properties of Agglomerates for Chemical Processes

NASA Astrophysics Data System (ADS)

Halt, Joseph A.

Iron ore pellets are hard spheres made from powdered ore and binders. Pellets are used to make iron, mainly in blast furnaces. Around the time that the pelletizing process was developed, starch was proposed as a binder because it's viscous, adheres well to iron oxides, does not contaminate pellets and is relatively cheap. In practice, however, starch leads to weak pellets with rough surfaces - these increase the amount of dust generated within process equipment and during pellet shipping and handling. Thus, even though the usual binder (bentonite clay) contaminates pellets, pelletizers prefer it to starch or other organics. This dissertation describes three ways to make good starch-based binders for pellets. Importantly, they solve the usual problems of weak rough pellets and lots of dust. The three approaches are: (1) Addition of clay to starch. This is not a novel idea. In fact, it is the standard method used for their improvement. However, it has not been tested extensively with starch. This approach was expected to be - and indeed was - successful. (2) Addition of a clay-rich layer to green ball surfaces. This approach is a novel idea. The coating's purpose was to mimic the good surface properties of standard bentonite-clay bonded pellets; as a benefit, clay consumption was significantly reduced. This approach was successful. (3) Addition of dispersants to starch. This approach was a novel idea. The intent of the dispersants was to enable pelletization to occur at lower moisture contents, thus leading to denser particle packing and lower porosity. The dispersants resulted in significantly stronger, smoother pellets without contaminating them with silica. Using approaches 1 and 3, starch can be used directly in traditional pelletizing operations, and importantly, in new pelletizing processes for new iron making operations. For approach 2, new application methods must be developed. Future engineering work is suggested as follows: design better dispersants for magnetic magnetite ores; incorporate the dispersing agent and starch into bead form for easy use; design a simple way to add coatings in existing drum-based pelletizing circuits; and optimize the coating composition to decrease both abrasion losses and pellet clustering (for new Direct Reduction pellets).

[Application of an artificial neural network in the design of sustained-release dosage forms].

PubMed

Wei, X H; Wu, J J; Liang, W Q

2001-09-01

To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

Reuse potential of low-calcium bottom ash as aggregate through pelletization.

PubMed

Geetha, S; Ramamurthy, K

2010-01-01

Coal combustion residues which include fly ash, bottom ash and boiler slag is one of the major pollutants as these residues require large land area for their disposal. Among these residues, utilization of bottom ash in the construction industry is very low. This paper explains the use of bottom ash through pelletization. Raw bottom ash could not be pelletized as such due to its coarseness. Though pulverized bottom ash could be pelletized, the pelletization efficiency was low, and the aggregates were too weak to withstand the handling stresses. To improve the pelletization efficiency, different clay and cementitious binders were used with bottom ash. The influence of different factors and their interaction effects were studied on the duration of pelletization process and the pelletization efficiency through fractional factorial design. Addition of binders facilitated conversion of low-calcium bottom ash into aggregates. To achieve maximum pelletization efficiency, the binder content and moisture requirements vary with type of binder. Addition of Ca(OH)(2) improved the (i) pelletization efficiency, (ii) reduced the duration of pelletization process from an average of 14-7 min, and (iii) reduced the binder dosage for a given pelletization efficiency. For aggregate with clay binders and cementitious binder, Ca(OH)(2) and binder dosage have significant effect in reducing the duration of pelletization process. 2010 Elsevier Ltd. All rights reserved.

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

NASA Astrophysics Data System (ADS)

Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

2011-12-01

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

PubMed

Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

2016-05-01

This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

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

PubMed

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

2010-01-01

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

Improved Bioavailability of Levodopa Using Floatable Spray-Coated Microcapsules for the Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Tee, Jie Kai; Pang, Yi Yun; Tan, Ern Yu; Lim, Kah Leong; Ho, Han Kiat; Loo, Say Chye Joachim

2018-06-01

Oral administration of levodopa (LD) is the gold standard in managing Parkinson's disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated with an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuations in plasma concentrations. To achieve a prolonged release of LD with the aim of improving its bioavailability, floatable spray-coated microcapsules containing all three PD drugs were developed. This gastro-retentive delivery system showed sustained release of all PD drugs, at similar release kinetics. Pharmacokinetics study was conducted and this newly developed formulation showed a more plateaued delivery of LD that is void of the plasma concentration fluctuations observed for the control (commercial formulation). At the same time, measurements of LD and dopamine of mice administered with this formulation showed enhanced bioavailability of LD. This study highlights a floatable, sustained-releasing delivery system in achieving improved pharmacokinetics data compared to a commercial formulation.

Glass-bonded iodosodalite waste form for immobilization of 129I

NASA Astrophysics Data System (ADS)

Chong, Saehwa; Peterson, Jacob A.; Riley, Brian J.; Tabada, Diana; Wall, Donald; Corkhill, Claire L.; McCloy, John S.

2018-06-01

Immobilization of radioiodine is an important requirement for current and future nuclear fuel cycles. Iodosodalite [Na8(AlSiO4)6I2] was synthesized hydrothermally from metakaolin, NaI, and NaOH. Dried unwashed sodalite powders were used to synthesize glass-bonded iodosodalite waste forms (glass composite materials) by heating pressed pellets at 650, 750, or 850 °C with two types of sodium borosilicate glass binders. These heat-treated specimens were characterized with X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, thermal analysis, porosity and density measurements, neutron activation analysis, and inductively-coupled plasma mass spectrometry. For the best waste form produced (pellets mixed with 10 mass% of glass binder and heat-treated at 750 °C), the maximum possible elemental iodine loading was 19.8 mass%, but only ∼8-9 mass% waste loading of iodine was retained in the waste form after thermal processing. Other pellets with higher iodine retention either contained higher porosity or were incompletely sintered. ASTM C1308 and C1285 (product consistency test, PCT) experiments were performed to understand chemical durability under diffusive and static conditions. The C1308 test resulted in significantly higher normalized loss compared to the C1285 test, most likely because of the strong effect of neutral pH solution renewal and prevention of ion saturation in solution. Both experiments indicated that release rates of Na and Si were higher than for Al and I, probably due to a poorly durable Na-Si-O phase from the glass bonding matrix or from initial sodalite synthesis; however the C1308 test result indicated that congruent dissolution of iodosodalite occurred. The average release rates of iodine obtained from C1308 were 0.17 and 1.29 g m-2 d-1 for 80 or 8 m-1, respectively, and the C1285 analysis gave a value of 2 × 10-5 g m-2 d-1, which is comparable to or better than the durability of other iodine waste forms.

Curing mechanism of flexible aqueous polymeric coatings.

PubMed

Irfan, Muhammad; Ahmed, Abid Riaz; Kolter, Karl; Bodmeier, Roland; Dashevskiy, Andriy

2017-06-01

The objective of this study was to explain curing phenomena for pellets coated with a flexible polymeric coating based on poly(vinyl acetate) (Kollicoat® SR 30D) with regard to the effect of starter cores, thickness of drug layer, adhesion of coating to drug-layered-cores as well as coating properties. In addition, appropriate approaches to eliminate the curing effect were identified. Sugar or MCC cores were layered with the model drugs carbamazepine, theophylline, propranolol HCl, tramadol HCl and metoprolol HCl using HPMC (5 or 25% w/w, based on drug) as a binder. Drug-layered pellets were coated with Kollicoat® SR 30D in a fluidized bed coater using TEC (10% w/w) as plasticizer and talc (35-100% w/w) as anti-tacking agent. Drug release, pellet properties (morphology, water uptake-weight loss and osmolality) and adhesion of the coating to the drug layer were investigated as a function of curing at 60°C or 60°C/75% RH for 24h. The film formation of the aqueous dispersion of Kollicoat® SR 30D was complete, and therefore, a strong curing effect (decrease in drug release) at elevated temperature and humidity (60°C/75% RH) could not be explained by the well-known hydroplasticization and the further gradual coalescence of the colloidal polymer particles. According to the provided mechanistic explanation, the observed curing effect was associated with (1) high flexibility of coating, (2) adhesion between coating and drug layer, (3) water retaining properties of the drug layer, and (4) osmotically active cores. Unwanted curing effects could be minimized/eliminated by the addition of talc or/and pore-forming water soluble polymers in the coating, increasing binder amount or applying an intermediate coating, by increasing the thickness of drug layer or using non-osmotic cores. A new insight into curing phenomena mainly associated with the adhesion between drug layer and coating was provided. Appropriate approaches to avoid unwanted curing effect were identified. Copyright © 2017 Elsevier B.V. All rights reserved.

High-rate behaviour of iron ore pellet

NASA Astrophysics Data System (ADS)

Gustafsson, Gustaf; Häggblad, Hans-Åke; Jonsén, Pär; Nishida, Masahiro

2015-09-01

Iron ore pellets are sintered, centimetre-sized spheres of ore with high iron content. Together with carbonized coal, iron ore pellets are used in the production of steel. In the transportation from the pelletizing plants to the customers, the iron ore pellets are exposed to different loading situations, resulting in degradation of strength and in some cases fragmentation. For future reliable numerical simulations of the handling and transportation of iron ore pellets, knowledge about their mechanical properties is needed. This paper describes the experimental work to investigate the dynamic mechanical properties of blast furnace iron ore pellets. To study the dynamic fracture of iron ore pellets a number of split Hopkinson pressure bar tests are carried out and analysed.

A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo.

PubMed

Galvin, Orla; Srivastava, Akshay; Carroll, Oliver; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Reynolds, Alison L; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon; Pandit, Abhay; Kennedy, Breandán N

2016-07-10

Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (p<0.0001) inhibited ocular developmental angiogenesis compared to control. Sustained amelioration of retinal vascular permeability (RVP) was demonstrated using a bespoke cysteinyl leukotriene induced rodent model. Quininib-HA microparticles significantly inhibited RVP in Brown Norway rats one month after administration compared to neat quininib control (p=0.0071). In summary, quininib-HA microneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

PubMed

Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

2016-01-01

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

PubMed

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

Microwave sensing of moisture in flowing biomass pellets

USDA-ARS?s Scientific Manuscript database

Production of pelleted biomass is a significant emerging industry in the United States. A primary quality attribute of pelleted biomass is moisture content. This parameter is critical in pricing, binding, combustion, and storage of pelleted biomass. In order to produce pellets of a high quality mois...

Design of sustained release tablet containing fucoidan.

PubMed

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

2015-01-01

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

A microstructural study of the degradation and calcium release from hydroxyapatite-calcium oxide ceramics made by infiltration.

PubMed

Zhang, Qinghao; Schmelzer, Eva; Gerlach, Jörg C; Nettleship, Ian

2017-04-01

Hydroxyapatite pellets, partially densified in a low-temperature heat treatment, were infiltrated with calcium nitrate solution followed by in-situ precipitation of Ca(OH) 2 and CaCO 3 . The infiltrated bodies were then densified to high relative density and the calcium carbonate transformed to calcium oxide during sintering and resulted in biphasic hydroxyapatite-CaO ceramics. This work investigated the influence of the infiltration on surface morphology, weight change, and microstructural-level degradation caused by exposure to saline at pH=7.4 and a temperature of 20°C. The CaO rendered the materials more susceptible to degradation, and released calcium into the saline faster than single phase, calcium deficient hydroxyapatite (HA) that were used as a control. In consequence, these ceramics could be used to release calcium into the culture microenvironments of bone tissue or bone marrow cells next to a scaffold surface. Copyright © 2016 Elsevier B.V. All rights reserved.

High burnup fuel behavior related to fission gas effects under reactivity initiated accidents (RIA) conditions

NASA Astrophysics Data System (ADS)

Lemoine, F.

1997-09-01

Specific aspects of irradiated fuel result from the increasing retention of gaseous and volatile fission products with burnup, which, under overpower conditions, can lead to solid fuel pressurization and swelling causing severe PCMI (pellet clad mechanical interaction). In order to assess the reliability of high burnup fuel under RIAs, experimental programs have been initiated which have provided important data concerning the transient fission gas behavior and the clad loading mechanisms. The importance of the rim zone is demonstrated based on three experiments resulting in clad failure at low enthalpy, which are explained by energetic considerations. High gas release in non-failure tests with low energy deposition underlines the importance of grain boundary and porosity gas. Measured final releases are strongly correlated to the microstructure evolution, depending on energy deposition, pulse width, initial and refabricated fuel rod design. Observed helium release can also increase internal pressure and gives hints to the gas behavior understanding.

Modeling pellet impact drilling process

NASA Astrophysics Data System (ADS)

Kovalyov, A. V.; Ryabchikov, S. Ya; Isaev, Ye D.; Ulyanova, O. S.

2016-03-01

The paper describes pellet impact drilling which could be used to increase the drilling speed and the rate of penetration when drilling hard rocks. Pellet impact drilling implies rock destruction by metal pellets with high kinetic energy in the immediate vicinity of the earth formation encountered. The pellets are circulated in the bottom hole by a high velocity fluid jet, which is the principle component of the ejector pellet impact drill bit. The experiments conducted has allowed modeling the process of pellet impact drilling, which creates the scientific and methodological basis for engineering design of drilling operations under different geo-technical conditions.

Formation of particulate matter monitoring during combustion of wood pellete with additives

NASA Astrophysics Data System (ADS)

Palacka, Matej; Holubčík, Michal; Vician, Peter; Jandačka, Jozef

2016-06-01

Application additives into the material for the production of wood pellets achieve an improvement in some properties such as pellets ash flow temperature and abrasion resistance. Additives their properties influence the course of combustion, and have an impact on the results of issuance. The experiment were selected additives corn starch and dolomite. Wood pellets were produced in the pelleting press and pelletizing with the additives. Selected samples were tested for the production of particulate matter (PM) during their direct burn. The paper analyzing a process of producing wood pellets and his effect on the final properties.

Durable regenerable sorbent pellets for removal of hydrogen sulfide from coal gas

DOEpatents

Siriwardane, R.V.

1999-02-02

Pellets for removing hydrogen sulfide from a coal gasification stream at an elevated temperature are prepared in durable form, usable over repeated cycles of absorption and regeneration. The pellets include a material reactive with hydrogen sulfide, in particular zinc oxide, a binder, and an inert material, in particular calcium sulfate (drierite), having a particle size substantially larger than other components of the pellets. A second inert material and a promoter may also be included. Preparation of the pellets may be carried out by dry, solid-state mixing of components, moistening the mixture, and agglomerating it into pellets, followed by drying and calcining. Pellet size is selected, depending on the type of reaction bed for which the pellets are intended. The use of inert material with a large particle size provides a stable pellet structure with increased porosity, enabling effective gas contact and prolonged mechanical durability.

Durable regenerable sorbent pellets for removal of hydrogen sulfide from coal gas

DOEpatents

Siriwardane, R.V.

1997-12-30

Pellets for removing hydrogen sulfide from a coal gasification stream at an elevated temperature are prepared in durable form usable over repeated cycles of absorption and regeneration. The pellets include a material reactive with hydrogen sulfide, in particular zinc oxide, a binder, and an inert material, in particular calcium sulfate (drierite), having a particle size substantially larger than other components of the pellets. A second inert material and a promoter may also be included. Preparation of the pellets may be carried out by dry, solid-state mixing of components, moistening the mixture, and agglomerating it into pellets, followed by drying and calcining. Pellet size is selected, depending on the type of reaction bed for which the pellets are intended. The use of inert material with a large particle size provides a stable pellet structure with increased porosity, enabling effective gas contact and prolonged mechanical durability.

Techno-economic assessment of pellets produced from steam pretreated biomass feedstock

DOE PAGES

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit; ...

2016-03-10

Minimum production cost and optimum plant size are determined for pellet plants for three types of biomass feedstock e forest residue, agricultural residue, and energy crops. The life cycle cost from harvesting to the delivery of the pellets to the co-firing facility is evaluated. The cost varies from 95 to 105 t -1 for regular pellets and 146–156 t -1 for steam pretreated pellets. The difference in the cost of producing regular and steam pretreated pellets per unit energy is in the range of 2e3 GJ -1. The economic optimum plant size (i.e., the size at which pellet production costmore » is minimum) is found to be 190 kt for regular pellet production and 250 kt for steam pretreated pellet. Furthermore, sensitivity and uncertainty analyses were carried out to identify sensitivity parameters and effects of model error.« less

Durable regenerable sorbent pellets for removal of hydrogen sulfide from coal gas

DOEpatents

Siriwardane, Ranjani V.

1997-01-01

Pellets for removing hydrogen sulfide from a coal gasification stream at an elevated temperature are prepared in durable form usable over repeated cycles of absorption and regeneration. The pellets include a material reactive with hydrogen sulfide, in particular zinc oxide, a binder, and an inert material, in particular calcium sulfate (drierite), having a particle size substantially larger than other components of the pellets. A second inert material and a promoter may also be included. Preparation of the pellets may be carried out by dry, solid-state mixing of components, moistening the mixture, and agglomerating it into pellets, followed by drying and calcining. Pellet size is selected, depending on the type of reaction bed for which the pellets are intended. The use of inert material with a large particle size provides a stable pellet structure with increased porosity, enabling effective gas contact and prolonged mechanical durability.

Durable regenerable sorbent pellets for removal of hydrogen sulfide coal gas

DOEpatents

Siriwardane, Ranjani V.

1999-01-01

Pellets for removing hydrogen sulfide from a coal gasification stream at an elevated temperature are prepared in durable form, usable over repeated cycles of absorption and regeneration. The pellets include a material reactive with hydrogen sulfide, in particular zinc oxide, a binder, and an inert material, in particular calcium sulfate (drierite), having a particle size substantially larger than other components of the pellets. A second inert material and a promoter may also be included. Preparation of the pellets may be carried out by dry, solid-state mixing of components, moistening the mixture, and agglomerating it into pellets, followed by drying and calcining. Pellet size is selected, depending on the type of reaction bed for which the pellets are intended. The use of inert material with a large particle size provides a stable pellet structure with increased porosity, enabling effective gas contact and prolonged mechanical durability.

Contributions to advances in blend pellet products (BPP) research on molecular structure and molecular nutrition interaction by advanced synchrotron and globar molecular (Micro)spectroscopy.

PubMed

Guevara-Oquendo, Víctor H; Zhang, Huihua; Yu, Peiqiang

2018-04-13

To date, advanced synchrotron-based and globar-sourced techniques are almost unknown to food and feed scientists. There has been little application of these advanced techniques to study blend pellet products at a molecular level. This article aims to provide recent research on advanced synchrotron and globar vibrational molecular spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction. How processing induced molecular structure changes in relation to nutrient availability and utilization of the blend pellet products. The study reviews Utilization of co-product components for blend pellet product in North America; Utilization and benefits of inclusion of pulse screenings; Utilization of additives in blend pellet products; Application of pellet processing in blend pellet products; Conventional evaluation techniques and methods for blend pellet products. The study focus on recent applications of cutting-edge vibrational molecular spectroscopy for molecular structure and molecular structure association with nutrient utilization in blend pellet products. The information described in this article gives better insight on how advanced molecular (micro)spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction.

Volume measurement of cryogenic deuterium pellets by Bayesian analysis of single shadowgraphy images

NASA Astrophysics Data System (ADS)

Szepesi, T.; Kálvin, S.; Kocsis, G.; Lang, P. T.; Wittmann, C.

2008-03-01

In situ commissioning of the Blower-gun injector for launching cryogenic deuterium pellets at ASDEX Upgrade tokamak was performed. This injector is designed for high repetitive launch of small pellets for edge localised modes pacing experiments. During the investigation the final injection geometry was simulated with pellets passing to the torus through a 5.5m long guiding tube. For investigation of pellet quality at launch and after tube passage laser flash camera shadowgraphy diagnostic units before and after the tube were installed. As indicator of pellet quality we adopted the pellet mass represented by the volume of the main remaining pellet fragment. Since only two-dimensional (2D) shadow images were obtained, a reconstruction of the full three-dimensional pellet body had to be performed. For this the image was first converted into a 1-bit version prescribing an exact 2D contour. From this contour the expected value of the volume was calculated by Bayesian analysis taking into account the likely cylindrical shape of the pellet. Under appropriate injection conditions sound pellets with more than half of their nominal mass are detected after acceleration; the passage causes in average an additional loss of about 40% to the launched mass. Analyzing pellets arriving at tube exit allowed for deriving the injector's optimized operational conditions. For these more than 90% of the pellets were arriving with sound quality when operating in the frequency range 5-50Hz.

Particle fueling experiments with a series of pellets in LHD

NASA Astrophysics Data System (ADS)

Baldzuhn, J.; Damm, H.; Dinklage, A.; Sakamoto, R.; Motojima, G.; Yasuhara, R.; Ida, K.; Yamada, H.; LHD Experiment Group; Wendelstein 7-X Team

2018-03-01

Ice pellet injection is performed in the heliotron Large Helical Device (LHD). The pellets are injected in short series, with up to eight individual pellets. Parameter variations are performed for the pellet ice isotopes, the LHD magnetic configurations, the heating scenario, and some others. These experiments are performed in order to find out whether deeper fueling can be achieved with a series of pellets compared to single pellets. An increase of the fueling efficiency is expected since pre-cooling of the plasma by the first pellets within a series could aid deeper penetration of later pellets in the same series. In addition, these experiments show which boundary conditions must be fulfilled to optimize the technique. The high-field side injection of pellets, as proposed for deep fueling in a tokamak, will not be feasible with the same efficiency in a stellarator or heliotron because there the magnetic field gradient is smaller than in a tokamak of comparable size. Hence, too shallow pellet fueling, in particular in a large device or a fusion reactor, will be an issue that can be overcome only by extremely high pellet velocities, or other techniques that will have to be developed in the future. It turned out by our investigations that the fueling efficiency can be enhanced by the injection of a series of pellets to some extent. However, further investigations will be needed in order to optimize this approach for deep particle fueling.

Effect of process variables on the quality characteristics of pelleted wheat distiller's dried grains with solubles

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

Jaya Shankar Tumuluru; Lope Tabil; Anthony Opoku

2011-04-01

The rapid expansion of ethanol processing plants in Canada has resulted in a significant increase in the production of wheat-based distiller's dried grains with solubles (DDGS). Transportation and flowability problems associated with DDGS necessitate investigations on pelleting. In the present study, the effect of process variables like die temperature (T) and feed moisture content (Mw) on the pellet properties like pellet moisture content, durability and pellet density was explored using a single pelleting machine; further studies on pelleting DDGS using a pilot-scale pellet mill were also conducted to understand the effect of die diameter and steam conditioning on durability andmore » bulk density of pellets. Proximate analysis of DDGS indicated that crude protein and dry matter were in the range of 37.37–40.33% and 91.27–92.60%, respectively. Linear regression models developed for pellet quality attributes like pellet moisture content, pellet density and durability adequately described the single pelleting process with R2 value of 0.97, 0.99 and 0.7, respectively. ANOVA results have indicated that linear terms T and Mw and the interaction term T × Mw were statistically significant at P < 0.01 and P < 0.1 for pellet moisture content and pellet density. Based on the trends of the surface plots, a medium T of about 50–80 °C and a low Mw of about 5.1% resulted in maximum pellet density and durability and minimum pellet moisture content. Results from pilot-scale studies indicated that bulk density, durability and throughput values were 436.8–528.9 kg m-3, 60.3–92.7% and 45.52–68.77 kg h-1, respectively. It was observed that both die diameter and steam addition had a significant effect on the bulk density and the durability values. The highest bulk density and durability were achieved with 6.4 mm die diameter with steam addition compared to 7.9 mm die with or without steam addition.« less

Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants.

PubMed

Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

2015-08-01

Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg(2+)-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants

NASA Astrophysics Data System (ADS)

Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

2015-08-01

Objective. Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. Approach. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Main results. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg2+-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. Significance. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

PubMed

Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

2017-11-01

Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren ® SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

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.

Polymer grafted-magnetic halloysite nanotube for controlled and sustained release of cationic drug.

PubMed

Fizir, Meriem; Dramou, Pierre; Zhang, Kai; Sun, Cheng; Pham-Huy, Chuong; He, Hua

2017-11-01

In this research, novel polymer grafted-magnetic halloysite nanotubes with norfloxacin loaded (NOR-MHNTs) and controlled-release, was achieved by surface-initiated precipitation polymerization. The magnetic halloysite nanotubes exhibited better adsorption of NOR (72.10mgg -1 ) compared with the pristine HNTs (30.80mgg -1 ). Various parameters influencing the drug adsorption of the MHNTs for NOR were studied. Polymer grafted NOR-MHNTs has been designed using flexible docking in computer simulation to choose optimal monomers. NOR-MHNTs/poly (methacrylic acid or acrylamide-co-ethylene glycol dimethacrylate) nanocomposite were synthesized using NOR-MHNTs, methacrylic acid (MAA) or acrylamide (AM), ethylene glycol dimethacrylate (EGDMA) and AIBN as nanotemplate, monomers, cross linker and initiator, respectively. The magnetic nanocomposites were characterized by FTIR, TEM, XRD and VSM. The magnetic nanocomposites show superparamagnetic property and fast magnetic response (12.09emug -1 ). The copolymerization of monomers and cross linker led to a better sustained release of norfloxacin (>60h) due to the strong interaction formed between monomers and this cationic drug. The cumulative release rate of NOR is closely related to the cross linker amount. In conclusion, combining the advantages of the high adsorption capacity and magnetic proprieties of this biocompatible clay nanotube and the advantages of polymer shell in the enhancement of controlled-sustained release of cationic drug, a novel formulation for the sustained-controlled release of bioactive agents is developed and may have considerable potential application in targeting drug delivery system. Copyright © 2017. Published by Elsevier Inc.

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

Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

PubMed Central

Jogala, Satheesh; Rachamalla, Shyam Sunder; Aukunuru, Jithan

2015-01-01

The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c.) nanoparticles of low molecular weight heparin (LMWH). The nanoparticles were prepared by water–in-oil in-water (w/o/w) emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15), and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1%) aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity) using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16–38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH. PMID:25878975

Sustained ophthalmic delivery of highly soluble drug using pH-triggered inner layer-embedded contact lens.

PubMed

Zhu, Qiang; Cheng, Hongbo; Huo, Yingnan; Mao, Shirui

2018-06-10

In the present work the feasibility of using inner layer-embedded contact lenses (CLs) to achieve sustained release of highly water soluble drug, betaxolol hydrochloride (BH) on the ocular surface was investigated. Blend film of cellulose acetate and Eudragit S100 was selected as the inner layer, while silicone hydrogel was used as outer layer to construct inner layer-embedded contact lenses. Influence of polymer ratio in the blend film on in vitro drug release behavior in phosphate buffered solution or simulated tear fluid was studied and drug-polymer interaction, erosion and swelling of the blend film were characterized to better understand drug-release mechanism. Storage stability of the inner layer-embedded contact lenses in phosphate buffer solution was also conducted, with ignorable drug loss and negligible change in drug release pattern within 30 days. In vivo pharmacokinetic study in rabbits showed sustained drug release for over 240 h in tear fluid, indicating prolonged drug precorneal residence time. In conclusion, cellulose acetate/Eudragit S100 inner layer-embedded contact lenses are quite promising as controlled-release carrier of highly water soluble drug for ophthalmic delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

PubMed

Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

2015-01-01

Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies.

PubMed

Kilicarslan, Muge; Koerber, Martin; Bodmeier, Roland

2014-05-01

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

Effect of micropatterning induced surface hydrophobicity on drug release from electrospun cellulose acetate nanofibers

NASA Astrophysics Data System (ADS)

Adepu, Shivakalyani; Gaydhane, Mrunalini K.; Kakunuri, Manohar; Sharma, Chandra S.; Khandelwal, Mudrika; Eichhorn, Stephen J.

2017-12-01

Sustained release and prevention of burst release for low half-life drugs like Diclofenac sodium is crucial to prevent drug related toxicity. Electrospun nanofibers have emerged recently as potential carrier materials for controlled and sustained drug release. Here, we present a facile method to prevent burst release by tuning the surface wettability through template assisted micropatterning of drug loaded electrospun cellulose acetate (CA) nanofibers. A known amount of drug (Diclofenac sodium) was first mixed with CA and then electrospun in the form of a nanofabric. This as-spun network was hydrophilic in nature. However, when electrospinning was carried out through non-conducting templates, viz nylon meshes with 50 and 100 μm size openings, two kinds of hydrophobic micro-patterned CA nanofabrics were produced. In vitro transdermal testing of our nanofibrous mats was carried out; these tests were able to show that it would be possible to create a patch for transdermal drug release. Further, our results show that with optimized micro-patterned dimensions, a zero order sustained drug release of up to 12 h may be achieved for the transdermal system when compared to non-patterned samples. This patterning caused a change in the surface wettability, to a hydrophobic surface, resulting in a controlled diffusion of the hydrophilic drug. Patterning assisted in controlling the initial burst release, which is a significant finding especially for low half-life drugs.

Sinkers or floaters? Contribution from salp pellets to the export flux during a large bloom event in the Southern Ocean

NASA Astrophysics Data System (ADS)

Iversen, Morten H.; Pakhomov, Evgeny A.; Hunt, Brian P. V.; van der Jagt, Helga; Wolf-Gladrow, Dieter; Klaas, Christine

2017-04-01

Salp fecal pellets are rich in organic matter and have been shown to sink at very high velocities. In recent years, salp abundances have been increasing in the Southern Ocean where they seem to be replacing krill as the dominant grazers on phytoplankton. As salps can form large swarms with high pellet production rates, it has been suggested that they will become increasingly important for the vertical export of particulate organic matter in the Southern Ocean. However, detailed studies combining both investigations of pellet production rates, turnover, and export are still needed in order to determine whether salp pellets are important for export ('sinkers') or recycling ('floaters') of organic matter. Our results suggest that pellets are produced at high rates in the upper few hundred meters of the water column. Although we observed high sinking velocities and low microbial degradation rates of the produced salp pellets, only about one third of the produced pellets were captured in sediment traps placed at 100 m and about 13% of the produced pellets were exported to sediment traps placed at 300 m. The high retention of these fast-settling pellets seems to be caused by break-up and loosening of the pellets, possibly by zooplankton and salps themselves. We measured 3-fold lower size-specific sinking velocities in loosened and fragmented compared to freshly produced intact pellets-. This enhanced the residence times (>1 day) of both small and large pellets in the upper water column. We postulate that the fragile nature of salp pellets make them more important for recycling of organic matter in the upper mesopelagic layer rather than as a conduit for export of particulate organic matter to the seafloor.

The Effect of Different Feed and Stocking Densities on Growth And Survival Rate Of Blue Swimming Crablets (Portunus pelagicus)

NASA Astrophysics Data System (ADS)

Ariyati, R. W.; Rejeki, S.; Bosma, R. H.

2018-02-01

Blue swimming crab is targeted by commercial fisheries because of the high economic value, good taste, and attractive colors. As a result, the stock is overexploited and fisherman catch market also juveniles. The most sustainable solution would be to stop fishing for commercial trade and to culture this crab from brood to market size. This study aimed to find the best feed and stocking density for the on-growing of crablets. In 20 tanks juvenile crabs with a carapace width±1 cm were stocked in three densities; 40, 60 and 80 crablets / m2, and fed ad-libitum twice a day with either trash fish or pellets of shrimp feed, for 8 weeks. The circular (ᴓ 1.6 m x 1 m) tanks with 1 m3 of water were aerated, and temperature, salinity, dissolved oxygen and pH recorded daily. In the end, growth and survival rates were determined. In general, feeding the crablets at a density of 40 m-2 gave the highest growth. For crablest fed with pellets, the density of 40 m-2 gave significantly better growth than 80 m-2. The crablets at a density 40 m-2 having a fish diet with the density 40 m-2 grew better than 60 and 80 m-2. There was no significant difference between fed used among different densities. The lower densities resulted in higher survival, either on crablets fed with pellets or fish. But, crablets fed the fish diet and cultured in the lowest density (40 m-2) had the highest survival rate.

Dosing of adult pigeons with as little as one #9 lead pellet caused severe δ-ALAD depression, suggesting potential adverse effects in wild populations.

PubMed

Holladay, Jeremy P; Nisanian, Mandy; Williams, Susan; Tuckfield, R Cary; Kerr, Richard; Jarrett, Timothy; Tannenbaum, Lawrence; Holladay, Steven D; Sharma, Ajay; Gogal, Robert M

2012-11-01

Avian wildlife species commonly ingest lead (Pb) spent shot or bullet fragments as grit or mistakenly as food. In previous studies in our laboratory and others, the toxicity varied based on the diet as well as type and quantity of Pb ingested. In the current study, domestic pigeons were gavaged with 1, 2, or 3 Pb pellets and then followed with weekly radiographs and blood physiologic endpoints for 28 days. Pellet retention decreased by roughly 50 % per week as pellets were either absorbed or excreted, except for week 4 where pellet number no longer was diminished. Size of retained pellets visually decreased over retention time. Birds dosed with a single #9 pellet showed mean blood Pb levels over 80 times higher than those of the controls, verifying Pb pellet absorption from the gut. A single Pb pellet also reduced plasma δ-aminolevulinic acid dehydratase (δ-ALAD) activity by over 80 % compared to controls, suggesting the potential for population injury in Pb pellet-exposed pigeons.

Measurement of Persistent Organic Pollutants (POPs) in plastic resin pellets from remote islands : Toward establishment of baseline level for International Pellet Watch

NASA Astrophysics Data System (ADS)

Takada, H.; Heskett, M.; Yamashita, R.; Yuyama, M.; Itoh, M.; Geok, Y. B.; Ogata, Y.

2011-12-01

Plastic resin pellets collected from remote islands in open oceans (Canary, St. Helena, Cocos, Hawaii, Maui Islands and Barbados) were sorted and yellowing polyethylene (PE) pellets were measured for polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and the degradation products (DDTs), and hexachlorocyclohexanes (HCHs) by gas chromatograph equipped with mass spectrometer (GC-MS) and with electron capture detector (GC-ECD). PCBs were detected from all the pellet samples, confirming the global dispersion of PCBs. Median concentrations of PCBs (sum of 13 congeners : CB-66, CB-101, CB-110, CB-118, CB-105, CB-149, CB-153, CB-138, CB-128, CB-187, CB-180, CB-170, CB-206) in the remote island pellets ranged from 0.1 to 10 ng/g-pellet. These were one to three orders of magnitude lower than those observed for pellets from industrialized coastal zones (hundreds ng/g in Los Angeles, Boston, Tokyo; Ogata et al., 2009). Because these remote islands are far (>100 km) from industrialized zones, these concentrations (i.e., 0.1 to 10 ng/g-pellet) can be regarded as global "baseline" level of PCB pollution. Concentrations of DDTs in the remote island pellets ranged from 0.2 to 5.5 ng/g-pellet. At some locations, DDT was dominant over the degradation products (DDE and DDD), suggesting current usage of the pesticides in the islands. HCHs concentrations were 0.4 - 1.8 ng/g-pellet and lower than PCBs and DDTs, except for St. Helena Island at 18.8 ng/g-pellet where the current usage of the pesticides are of concern. The analyses of pellets from the remote islands provided "baseline" level of POPs (PCBs < 10 ng/g-pellet, DDTs < 6 ng/g-pellet, HCHs < 2 ng/g-pellet). However, the present samples were from tropical and subtropical areas. To establish global baseline, especially to understand the effects of global distillation, pellet samples from remote islands in higher latitude regions are necessary. From the eco-toxicological point of view, the fact that sporadic high concentrations of POPs were detected in some pellet samples from the remote islands is underscored. Some plastic debris which were contaminated in industrialized coastal zones may have rapidly transported to the remote islands before they would reach equilibrium (i.e., desorption completed). Because POPs concentrations in the other media are at trace levels in these remote environments, the sporadic high concentrations of POPs in the plastic debris may pose threat to the ecosystem in the remote islands.

Sustainable and Healthy Communities (SHC) Topic 3 Fact Sheets

EPA Pesticide Factsheets

These documents provide a condensed overview of the Sustainable and Healthy Communities (SHC) Research Program's Projects 3.61 Contaminated Sites, 3.62 Environmental Releases of Oils and Fuels, and 3.63 Sustainable Materials Management.

Feasibility of localized immunosuppression: 3. Preliminary evaluation of organosilicone constructs designed for sustained drug release in a cell transplant environment using dexamethasone.

PubMed

Song, Y; Margolles-Clark, E; Fraker, C A; Weaver, J D; Ricordi, C; Pileggi, A; Stabler, C L; Buchwald, P

2012-05-01

As part of our ongoing effort to develop biohybrid devices for pancreatic islet transplantation, we are interested in establishing the feasibility of a localized immune-suppressive approach to avoid or minimize the undesirable side effects of existing systemic treatments. Since biohybrid devices can also incorporate biocompatible scaffold constructs to provide a support environment for the transplanted cells that enhances their engraftment and long-term function, we are particularly interested in an approach that would use the same three-dimensional construct, or part of the same construct, to also provide sustained release of therapeutic agents to modulate the inflammatory and immune responses locally. Within this framework, here, we report preliminary results obtained during the investigation of the suitability of organosilicone constructs for providing sustained localized drug release using small, matrix-type polydimethylsiloxane (PDMS) disks and dexamethasone as a model hydrophobic drug. Following a short burst, long-term steady sustained release was observed under in vitro conditions at levels of 0.1-0.5 microg/day/disk with a profile in excellent agreement with that predicted by the Higuchi equation. To verify that therapeutic levels can be achieved, suppression of LPS-induced activation has been shown in THP-1 cells with disks that have been pre-soaked for up to 28 days. These preliminary results prove the feasibility of this approach where an integral part of the biomaterial construct used to enhance cell engraftment and long-term function also serves to provide sustained local drug release.

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

PubMed

Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

2018-02-14

To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

Native and microwave-modified Terminalia mantaly gums as sustained-release and bioadhesive excipients in naproxen matrix tablet formulations.

PubMed

Odeniyi, Michael Ayodele; Oyedokun, Babatunde Mukhtar; Bamiro, Oluyemisi Adebowale

2017-01-01

Hydrophilic polymers provide a means of sustaining drug delivery. Native gums may be limited in function, but modification may improve their activity. The aim of the study was to evaluate native and modified forms of Terminalia mantaly gum for their sustained-release and bioadhesive properties. The native gum (NTM) was modified by microwave irradiation for 20 seconds (MTM20) and 60 seconds (MTM60) and characterized using microscopy, Fourier transform infrared spectroscopy (FTIR) and packing properties. The effects of the thermally induced molecular reorientation were determined. Tablet formulations of naproxen were produced by direct compression. The mechanical, bioadhesive and release properties of the formulations were determined. Irradiation of NTM improved the gum's flow properties, resulting in Carr's Index and Hausner's ratios lower than 16% and 1.25, respectively. Swelling studies showed that MTM20 and MTM60 had lower water absorption capacity and swelling index values, while packing properties improved upon irradiation, as depicted by lower tapped density values. FTIR spectra of samples showed that the irradiated gums were distinct from the native gums and did not interact with naproxen sodium. The gum's mechanical properties improved with MTM20 and MTM60 and sustained-release action of up 12 h was obtained. Inclusion of hydroxypropyl methylcellulose (HPMC) in the tablet formulations proved critical for bioadhesion. Microwave irradiation of native Terminalia mantaly gum improved the flow, mechanical and sustained-release properties of Naproxen tablets, and the addition of HPMC increased bioadhesion properties. The tablet properties of the native gum were significantly improved after 20 s of microwave irradiation.

Critical Science Issues for Direct Drive Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Dahlburg, Jill P.; Gardner, John H.; Schmitt, Andrew J.; Obenschain, S. P.

1998-09-01

There are several topics that require resolution prior to the construction of an Inertial Fusion Energy [IFE] laboratory Engineering Test Facility [ETF]: a pellet that produces high gain; a pellet fabrication system that cost-effectively and rapidly manufactures these pellets; a sufficiently uniform and durable high repetition-rate laser pellet driver; a practical target injection system that provides accurate pellet aiming; and, a target chamber that will survive the debris and radiation of repeated high-gain pellet implosions. In this summary we describe the science issues and opportunities that are involved in the design of a successful high gain direct drive Inertial Confinement Fusion [ICF] pellet.

Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

2016-06-15

Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization.

PubMed

Harsha, Sree

2013-01-01

Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology--the Büchi Nano Spray Dryer B-90 - and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm(3). In vitro drug release of formulations was best fitted by first-order and Peppas models with R (2) of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25 °C ± 2 °C and 60% ± 5% relative humidity.

Influence of apple pomace inclusion on the process of animal feed pelleting.

PubMed

Maslovarić, Marijana D; Vukmirović, Đuro; Pezo, Lato; Čolović, Radmilo; Jovanović, Rade; Spasevski, Nedeljka; Tolimir, Nataša

2017-08-01

Apple pomace (AP) is the main by-product of apple juice production. Large amounts of this material disposed into landfills can cause serious environmental problems. One of the solutions is to utilise AP as animal feed. The aim of this study was to investigate the impact of dried AP inclusion into model mixtures made from conventional feedstuffs on pellet quality and pellet press performance. Three model mixtures, with different ratios of maize, sunflower meal and AP, were pelleted. Response surface methodology (RSM) was applied when designing the experiment. The simultaneous and interactive effects of apple pomace share (APS) in the mixtures, die thickness (DT) of the pellet press and initial moisture content of the mixtures (M), on pellet quality and production parameters were investigated. Principal component analysis (PCA) and standard score (SS) analysis were applied for comprehensive analysis of the experimental data. The increase in APS led to an improvement of pellet quality parameters: pellet durability index (PDI), hardness (H) and proportion of fines in pellets. The increase in DT and M resulted in pellet quality improvement. The increase in DT and APS resulted in higher energy consumption of the pellet press. APS was the most influential variable for PDI and H calculation, while APS and DT were the most influential variables in the calculation of pellet press energy consumption. PCA showed that the first two principal components could be considered sufficient for data representation. In conclusion, addition of dried AP to feed model mixtures significantly improved the quality of the pellets.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

PELLETS AND PELLETIZATION: EMERGING TRENDS IN THE PHARMA INDUSTRY.

PubMed

Zaman, Muhammad; Saeed-Ul-Hassan, Syed; Sarfraz, Rai Muhammad; Batool, Nighat; Qureshi, Muhammad Junaid; Akram, Muhammad Abdullah; Munir, Saiqa; Danish, Zeeshan

2016-11-01

The present time is considered as an era of advancements in drug delivery systems. Different novel approaches are under investigation that range from uniparticulate to multi particulate system, macro to micro and nano particulate systems. Pelletization is one of the novel drug delivery technique that provides an effective way to deliver the drug in modified pattern. It is advantageous in providing site specific delivery of the drug. Drugs with unpleasant taste, poor bioavailability and short biological half-life can be delivered efficiently through pellets. Their reduced size makes them more valuable as compared to the conventional drug deliv- ery system. Different techniques are used to fabricate the pellets such as extrusion and spheronization, hot melt extrusion, powder layering, suspension or solution layering, freeze pelletization and pelletization by direct compression method. Various natural polymers including xanthan gum, guar gum, tragacanth and gum acacia, semisynthetic polymers like cellulose derivatives, synthetic polymers like derivatives of acrylamides, can be used in pellets formulation. Information provided in this review is collected from various national and intemational research articles, review articles and literature available in the books. The purpose of the current review is to discuss pellets, their characterizations, different techniques of pelletization and the polymers with potential of being suitable for pellets formulation.

The Role of Biomass Composition and Steam Treatment on Durability of Pellets

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

Tang, Yong; Chandra, Richard P.; Sokhansanj, Shahab

Steam treatment has been reported to improve the durability of wood pellet likely by changing the physical and chemical structures of wood particles, but published literature is inconclusive about which structure change is the major reason for enhanced durability. Here, in this paper, steam treatment was combined either with alkaline or with SO 2 to study. The solids obtained after steam treatments along with a control sample were dried and each was compacted into pellets. The pellets were then tested for durability. Steam treatment alone dominated improvements in durability. The pellet durability increased with the amount of xylose, but xylosemore » performed better in the pellet from raw poplar than did in the pellet from treated poplar. Water-soluble components contributed a maximum 4% of the durability of poplar pellets. The addition of lignin and sugars to substrates after steam treatment did not improve durability significantly. The surface modification that took place as a result of size reduction during steam treatment was the major reason, contributing about 50% of the durability of the pellet from steam-treated poplar. The acidity of steam treatment slightly affected the relative contributions of these structure changes on the durability. Lastly, the new knowledge helps tailor the chemical and/or mechanical pretreatment involved in pelleting biomass to durable pellets.« less

The Role of Biomass Composition and Steam Treatment on Durability of Pellets

DOE PAGES

Tang, Yong; Chandra, Richard P.; Sokhansanj, Shahab; ...

2018-03-03

Steam treatment has been reported to improve the durability of wood pellet likely by changing the physical and chemical structures of wood particles, but published literature is inconclusive about which structure change is the major reason for enhanced durability. Here, in this paper, steam treatment was combined either with alkaline or with SO 2 to study. The solids obtained after steam treatments along with a control sample were dried and each was compacted into pellets. The pellets were then tested for durability. Steam treatment alone dominated improvements in durability. The pellet durability increased with the amount of xylose, but xylosemore » performed better in the pellet from raw poplar than did in the pellet from treated poplar. Water-soluble components contributed a maximum 4% of the durability of poplar pellets. The addition of lignin and sugars to substrates after steam treatment did not improve durability significantly. The surface modification that took place as a result of size reduction during steam treatment was the major reason, contributing about 50% of the durability of the pellet from steam-treated poplar. The acidity of steam treatment slightly affected the relative contributions of these structure changes on the durability. Lastly, the new knowledge helps tailor the chemical and/or mechanical pretreatment involved in pelleting biomass to durable pellets.« less

Monolith catalysts for closed-cycle carbon dioxide lasers

NASA Technical Reports Server (NTRS)

Herz, Richard K.; Badlani, Ajay

1991-01-01

The objective was to explore ways of making a monolithic form of catalyst for CO2 lasers. The approach chosen was to pelletize the catalyst material, Au/MnO2 powder, and epoxy the pellets to stainless steel sheets as structural supports. The CO oxidation reaction over Au/MnO2 powder was found to be first overall, and the reaction rate constant at room temperature was 4.4 +/- 0.3 cc/(g x sec). The activation energy was 5.7 kcal/mol. The BET surface area of the pellets was found to vary from 125 to 140 sq m/g between different batches of catalyst. Pellets epoxied to stainless steel strips showed no sign of fracture or dusting when subjected to thermal tests. Pellets can be dropped onto hard surfaces with chipping of edges but no breakage of the pellets. Mechanical strength tests performed on the pellets showed that the crush strength is roughly one-fourth of the pelletizing force. The apparent activity and activation energy over the pellets were found to be less than over the powdered form of the catalyst. The lower apparent activity and activation energy of the pellets are due to the fact that the internal surface area of a pellet is not exposed to the reactant concentration present in the flowing gas as a result of intrapellet diffusion resistance. Effectiveness factors varied from 0.44, for pellets having thickness of 2 mm and attached with epoxy to a stainless steel strip. The epoxy and the stainless steel strip were found to simply block off one of the circular faces of the pellets. The epoxy did not penetrate the pellets and block the active sites. The values of the effective diffusivities were estimated to be between 2.3 x 10(exp -3) and 4.9 x 10(exp -3) sq cm/s. With measurements performed on one powder sample and one pellet configuration, reasonable accurate predictions can be made of conversions that would be obtained with other pellet thickness and configurations.

Comparative Properties of Bamboo and Rice Straw Pellets

Treesearch

Xianmiao Liu; Zhijia Liu; Benhua Fei; Zhiyong Cai; Zehui Jiang; Xing' e Liu

2013-01-01

Bamboo is a potential major bio-energy resource. Tests were carried out to compare and evaluate the property of bamboo and rice straw pellets, rice straw being the other main source of biomass solid fuel in China. All physical properties of untreated bamboo pellets (UBP), untreated rice straw pellets (URP), carbonized bamboo pellets (CBP), and carbonized rice straw...

Encapsulation of thermal energy storage media

DOEpatents

Dhau, Jaspreet; Goswami, Dharendra; Jotshi, Chand K.; Stefanakos, Elias K.

2017-09-19

In one embodiment, a phase change material is encapsulated by forming a phase change material pellet, coating the pellet with flexible material, heating the coated pellet to melt the phase change material, wherein the phase change materials expands and air within the pellet diffuses out through the flexible material, and cooling the coated pellet to solidify the phase change material.

THE METABOLISM OF SILICON IN THE RAT AND ITS RELATION TO THE FORMATION OF ARTIFICIAL SILICEOUS CALCULI

PubMed Central

Keeler, Richard F.; Lovelace, Stuart A.

1959-01-01

The urinary excretion of silicon in the rat was found to be enhanced beyond normal levels by the administration of various chemical forms of silicon. The excretion was enhanced to a much greater degree by the administration of ethyl silicate than by magnesium trisilicate, sodium metasilicate, or water glass. The tolerance level of rats to sustained daily doses of ethyl silicate fed via stomach tube was approximately 15 to 30 mg. of silicon per rat per day. Urinary silicon excretion was found to be a straight line function of the concentration of ethyl silicate administered, via stomach tube, with approximately 18 per cent of the administered silicon appearing in the urine at all levels tested. Using sustained dietary additions of ethyl silicate as a means of enhancing urine silicon levels, artificial siliceous urinary calculi were consistently produced on zinc pellets implanted in the bladders of rats. PMID:13654631

Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease intended for colon-specific drug delivery.

PubMed

Freire, Cristina; Podczeck, Fridrun; Veiga, Francisco; Sousa, João

2010-02-01

Colon-specific delivery of drugs can be achieved with dosage forms coated with biopolymers that are metabolized selectively by the colonic microflora and yet resistant to enzymatic digestion in the small intestine. The aim of this study was to study the influence of formulation factors on the performance of mixed films from high-amylose starches and Surelease((R)), applied using a spray-coating process, as potential colon-specific delivery devices. 5-Aminosalicylic acid-loaded pellets were prepared by an extrusion-spheronization process and film coated with mixtures of the starches and Surelease((R)). Optimization of the coating formulation, that is, starch-to-Surelease((R)) ratio, film-coating thickness, and type of starch, was undertaken first in enzyme-free media resembling the conditions in the stomach and small intestine. The effect of curing of the film coating on the drug release profile upon storage was also evaluated. Optimized coating formulations were further assessed for enzymatic digestibility using artificial gastric and intestinal juices containing commercially available pepsin and pancreatin or alpha-amylase from hog pancreas, respectively. Finally, drug release was assessed in fluid-simulating conditions in the colon (SCF) containing Bacillus licheniformis alpha-amylase. Film coatings comprising high-amylose starches and Surelease((R)) in a ratio of 1:2 (w/w) and film thickness of approximately 45 microm were able to withstand the chemical and enzymatic environment of the upper gastrointestinal tract, in particular, resisted degradation by the pancreatic alpha-amylases. Stability of the coatings during storage was achieved with additional curing. In SCF, these coatings were susceptible to enzymatic degradation. This study showed that high amylose starch-mixed films can be successfully used as colon-specific delivery devices. The preparation of the coating dispersions described is simple and rapid, without the need to extract the amylose component of starch.

Assessment of microplastic toxicity to embryonic development of the sea urchin Lytechinus variegatus (Echinodermata: Echinoidea).

PubMed

Nobre, C R; Santana, M F M; Maluf, A; Cortez, F S; Cesar, A; Pereira, C D S; Turra, A

2015-03-15

Apart from the physiological impacts on marine organisms caused by ingesting microplastics, the toxicity caused by substances leaching from these particles into the environment requires investigation. To understand this potential risk, we evaluated the toxicity of virgin (raw) and beach-stranded plastic pellets to the development of embryos of Lytechinus variegatus, simulating transfers of chemical compounds to interstitial water and water column by assays of pellet-water interface and elutriate, respectively. Both assays showed that virgin pellets had toxic effects, increasing anomalous embryonic development by 58.1% and 66.5%, respectively. The toxicity of stranded pellets was lower than virgin pellets, and was observed only for pellet-water interface assay. These results show that (i) plastic pellets act as a vector of pollutants, especially for plastic additives found on virgin particles; and that (ii) the toxicity of leached chemicals from pellets depends on the exposure pathway and on the environmental compartment in which pellets accumulate. Copyright © 2015 Elsevier Ltd. All rights reserved.