Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality

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Alex Avdeef

2016-06-01

Full Text Available This commentary addresses data quality in equilibrium solubility measurement in aqueous solution. Broadly discussed is the “gold standard” shake-flask (SF method used to measure equilibrium solubility of ionizable drug-like molecules as a function of pH. Many factors affecting the quality of the measurement are recognized. Case studies illustrating the analysis of both solution and solid state aspects of solubility measurement are presented. Coverage includes drug aggregation in solution (sub-micellar, micellar, complexation, use of mass spectrometry to assess aggregation in saturated solutions, solid state characterization (salts, polymorphs, cocrystals, polymorph creation by potentiometric method, solubility type (water, buffer, intrinsic, temperature, ionic strength, pH measurement, buffer issues, critical knowledge of the pKa, equilibration time (stirring and sedimentation, separating solid from saturated solution, solution handling and adsorption to untreated surfaces, solubility units, and tabulation/graphic presentation of reported data. The goal is to present cohesive recommendations that could lead to better assay design, to result in improved quality of measurements, and to impart a deeper understanding of the underlying solution chemistry in suspensions of drug solids.

Effect of cyclodextrin complexation on the aqueous solubility and solubility/dose ratio of praziquantel.

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Maragos, Stratos; Archontaki, Helen; Macheras, Panos; Valsami, Georgia

2009-01-01

Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound like PZQ could behave as BCS-Class I (highly soluble/highly permeable) drug. Phase solubility and the kneading and lyophilization techniques were used for inclusion complex preparation; solubility was determined by UV spectroscopy. The ability of the water soluble polymer polyvinylpyrolidone (PVP) to increase the complexation and solubilization efficiency of beta-CD and HP-beta-CD for PZQ was examined. Results showed significant improvement of PZQ solubility in the presence of both cyclodextrins but no additional effect in the presence of PVP. The solubility/dose ratios values of PZQ-cyclodextrin complexes calculated considering the low (150 mg) and the high dose (600 mg) of PZQ, used in practice, indicate that PZQ complexation with CDs may result in drug dosage forms that would behave as a BCS-Class I depending on the administered dose.

Improving solubility and refolding efficiency of human V(H)s by a novel mutational approach.

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Tanha, Jamshid; Nguyen, Thanh-Dung; Ng, Andy; Ryan, Shannon; Ni, Feng; Mackenzie, Roger

2006-11-01

The antibody V(H) domains of camelids tend to be soluble and to resist aggregation, in contrast to human V(H) domains. For immunotherapy, attempts have therefore been made to improve the properties of human V(H)s by camelization of a small set of framework residues. Here, we have identified through sequence comparison of well-folded llama V(H) domains an alternative set of residues (not typically camelid) for mutation. Thus, the solubility and thermal refolding efficiency of a typical human V(H), derived from the human antibody BT32/A6, were improved by introduction of two mutations in framework region (FR) 1 and 4 to generate BT32/A6.L1. Three more mutations in FR3 of BT32/A6.L1 further improved the thermal refolding efficiency while retaining solubility and cooperative melting profiles. To demonstrate practical utility, BT32/A6.L1 was used to construct a phage display library from which were isolated human V(H)s with good antigen binding activity and solubility. The engineered human V(H) domains described here may be useful for immunotherapy, due to their expected low immunogenicity, and in applications involving transient high temperatures, due to their efficient refolding after thermal denaturation.

Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

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Ehsan Adeli

Full Text Available ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin, various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG. Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC, Powder X-Ray Diffraction (PXRD and Scanning Election Microscopy (SEM. In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously.

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Xing, Qiao; Song, Jia; You, Xiuhua; Xu, Dongling; Wang, Kexin; Song, Jiaqi; Guo, Qin; Li, Pengyu; Wu, Chuanbin; Hu, Haiyan

2016-09-25

Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions. However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate, an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC0-t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide, severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport. Copyright © 2016 Elsevier B.V. All rights reserved.

Overview of milling techniques for improving the solubility of poorly water-soluble drugs

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Zhi Hui Loh

2015-07-01

Full Text Available Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a “top–down” approach in the production of fine particles. Fine drug particulates are especially desired in formulations designed for parenteral, respiratory and transdermal use. Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents, often to enhance processability or solubility especially for drugs with limited aqueous solubility. The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size, specific surface area and shape of the drug particles as well as milling-induced amorphization and/or structural disordering of the drug crystal (mechanochemical activation. Technology advancements in milling now enable the production of drug micro- and nano-particles on a commercial scale with relative ease. This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs. Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

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Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

2017-01-01

Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer...... potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

Kaempferol-Phospholipid Complex: Formulation, and Evaluation of Improved Solubility, In Vivo Bioavailability, and Antioxidant Potential of Kaempferol

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Darshan R. Telange

2016-12-01

Full Text Available The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32 approach. Our results include the validation of the mathematical model in order to ascertain the role of specific formulation and process variables that contribute favorably to the formulation’s development. The final product was characterized and confirmed by Differential Scanning Calorimetry (DSC, Fourier Transform Infrared Spectroscopy (FTIR, Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR, and Powder X-ray Diffraction (PXRD analysis. The aqueous solubility and the in vitro dissolution rate were enhanced compared to that of pure kaempferol. The in vivo antioxidant properties of the kaempferol-phospholipid complex were evaluated by measuring its impact on carbon tetrachloride (CCl4-intoxicated rats. The optimized phospholipid complex improved the liver function test parameters to a significant level by restoration of all elevated liver marker enzymes in CCl4-intoxicated rats. The complex also enhanced the in vivo antioxidant potential by increasing levels of GSH (reduced glutathione, SOD (superoxide dismutase, catalase and decreasing lipid peroxidation, compared to that of pure kaempferol. The final optimized phospholipid complex also demonstrated a significant improvement in oral bioavailability demonstrated by improvements to key pharmacokinetic parameters, compared to that of pure kaempferol.

Improved Bilayer Resist System Using Contrast-Enhanced Lithography With Water-Soluble Photopolymer

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Sasago, Masaru; Endo, Masayuki; Hirai, Yoshihiko; Ogawa, Kazufurni; Ishihara, Takeshi

1986-07-01

A new water-soluble contract enhanced material, WSP (Water-soluble Photopolymer), has been developed. The WSP is composed of a mainpolymer and a photobleachable reagents. The mainpolymer is a water-soluble polymer mixed with pullulan (refined through biotechnological process) and polyvinyl-pyrolidone (PVP). The photo-bleachable reagent is of a diazonium compound gorup. The introduction of the mainpolymer and photobleach-able reagent mixture has improved filmity, gas transparency, photobleaching characteristics and solubility in alkaline which are essential to the device fabrication. Submicron photoresist patterns are successfully fabricated by a simple sequence of photolithography process. The WSP layer has been applied to the bilayer resist system--deep-UV portable conformable masking (PCM)--that is not affected by VLSI's topography, and is able to fabricate highly accurate pattern. The aqueous developable layer, PMGI, with high organic solvent resistance is used in the bottom layer. Therefore, no interfacial mixing with conventional positive resist top layer is observed. Furthermore, deep-UV exposure method has been used for the KrF excimer laser optical system in order to increase high throughput. From the experiments, it has been confirmed that good resist transfer profile can be realized by the use of WSP, and that the submicron resist patterns with high aspect-ratio can be developed on the nonplaner wafer with steps of up to 41m by the combination of the WSP with the PCM system. By this technology, has been improved the weak point: variation in the line width due to the thickness of contrast-enhanced layer when the CEL technology is applied, and dependency of both the finished resist profile and the line-width accuracy on the thickness of the top layer resist when the PCM system is adopted.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

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Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

An injectable hybrid nanoparticle-in-oil-in-water submicron emulsion for improved delivery of poorly soluble drugs

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Wang, Shuo; Wang, Hua; Liang, Wenquan; Huang, Yongzhuo

2012-04-01

Poor drugability problems are commonly seen in a class of chemical entities with poor solubility in water and oil, and moreover, physicochemical instability of these compounds poses extra challenges in design of dosage forms. Such problems contribute a significant high failure rate in new drug development. A hybrid nanoparicle-in-oil-in-water (N/O/W) submicron emulsion was proposed for improved delivery of poorly soluble and unstable drugs (e.g., dihydroartemisinin (DHA)). DHA is known for its potent antimalarial effect and antitumor activity. However, its insolubility and instability impose big challenges for formulations, and so far, no injectable dosage forms are clinically available yet. Therefore, an injectable DHA N/O/W system was developed. Unlike other widely-explored systems (e.g., liposomes, micelles, and emulsions), in which low drug load and only short-term storage are often found, the hybrid submicron emulsion possesses three-fold higher drug-loading capacity than the conventional O/W emulsion. Of note, it can be manufactured into a freeze-drying form and can render its storage up to 6 months even in room temperature. The in vivo studies demonstrated that the PK profiles were significantly improved, and this injectable system was effective in suppressing tumor growth. The strategy provides a useful solution to effective delivery of such a class of drugs.

Improving the water solubility of Monascus pigments under acidic conditions with gum arabic.

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Jian, Wenjie; Sun, Yuanming; Wu, Jian-Yong

2017-07-01

Monascus pigments (Mps) are natural food colorants and their stability in acidic solutions is important for application in the food industry. This study aimed to evaluate the use of gum arabic (GA) as a stabilizer for maintaining the solubility of Mps in an acidic aqueous solution exposed to a high temperature, and to analyze the molecular interactions between GA and Mps. Mps dispersed (0.2 g kg -1 ) in deionized water at pH 3.0-4.0 without GA formed precipitates but remained in a stable solution in the presence of GA (1 g kg -1 ). The significant improvement of Mps water solubility under acidic conditions was attributed to the formation of Mps-GA complexes, as indicated by a sharp increase in the fluorescence intensity. The results on particle size, zeta potential, and transmission electron microscopy further suggested that molecular binding of Mps to GA, electrostatic repulsion, and steric hindrance of GA were contributing factors to preventing the aggregation of Mps in acidic solutions. A mechanistic model was presented for GA-Mps interactions and complex structures. GA was proven to be an effective stabilizer of natural food colorants in acidic solutions. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

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Aude Lafoux

Full Text Available Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age. An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

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Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studies

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Ranjan, Subham; Devarapalli, Ramesh; Kundu, Sudeshna; Vangala, Venu R.; Ghosh, Animesh; Reddy, C. Malla

2017-04-01

Hydrochlorothiazide (HCT) is a diuretic BCS class IV drug with poor aqueous solubility and low permeability leading to poor oral absorption. The present work explores the cocrystallization technique to enhance the aqueous solubility of HCT. Three new cocrystals of HCT with water soluble coformers phenazine (PHEN), 4-dimethylaminopyridine (DMAP) and picolinamide (PICA) were prepared successfully by solution crystallization method and characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), fourier transform -infraredspectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Structural characterization revealed that the cocrystals with PHEN, DMAP and PICA exists in P21/n, P21/c and P21/n space groups, respectively. The improved solubility of HCT-DMAP (4 fold) and HCT-PHEN (1.4 fold) cocrystals whereas decreased solubility of HCT-PICA (0.5 fold) as compared to the free drug were determined after 4 h in phosphate buffer, pH 7.4, at 25 °C by using shaking flask method. HCT-DMAP showed a significant increase in solubility than all previously reported cocrystals of HCT suggest the role of a coformer. The study demonstrates that the selection of coformer could have pronounced impact on the physicochemical properties of HCT and cocrystallization can be a promising approach to improve aqueous solubility of drugs.

The solubilities of significant organic compounds in HLW tank supernate solutions -- FY 1995 progress report

International Nuclear Information System (INIS)

Barney, G.S.

1996-01-01

At the Hanford Site organic compounds were measured in tank supernate simulant solutions during FY 1995. This solubility information will be used to determine if these organic salts could exist in solid phases (saltcake or sludges) in the waste where they might react violently with the nitrate or nitrite salts present in the tanks. Solubilities of sodium glycolate, succinate, and caproate salts; iron and aluminum and butylphosphate salts; and aluminum oxalate were measured in simulated waste supernate solutions at 25 degree C, 30 degree C, 40 degree C, and 50 degree C. The organic compounds were selected because they are expected to exist in relatively high concentrations in the tanks. The solubilities of sodium glycolate, succinate, caproate, and butylphosphate in HLW tank supernate solutions were high over the temperature and sodium hydroxide concentration ranges expected in the tanks. High solubilities will prevent solid sodium salts of these organic acids from precipitating from tank supernate solutions. The total organic carbon concentrations (YOC) of actual tank supernates are generally much lower than the TOC ranges for simulated supernate solutions saturated (at the solubility limit) with the organic salts. This is so even if all the dissolved carbon in a given tank and supernate is due to only one of these eight soluble compounds (an unlikely situation). Metal ion complexes of and butylphosphate and oxalate in supernate solutions were not stable in the presence of the hydroxide concentrations expected in most tanks. Iron and aluminum dibutylphosphate compounds reacted with hydroxide to form soluble sodium dibutylphosphate and precipitated iron and aluminum hydroxides. Aluminum oxalate complexes were also not stable in the basic simulated supernate solutions. Solubilities of all the organic salts decrease with increasing sodium hydroxide concentration because of the common ion effect of Na+. Increasing temperatures raised the solubilities of the organic

Changing oxidoreduction potential to improve water-soluble yellow pigment production with Monascus ruber CGMCC 10910.

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Huang, Tao; Tan, Hailing; Lu, Fangju; Chen, Gong; Wu, Zhenqiang

2017-11-21

Monascus pigments are widely used in the food and pharmaceutical industries due to their safety to human health. Our previous study found that glucose concentration induced extracellular oxidoreduction potential (ORP) changes could influence extracellular water-soluble yellow pigment production by Monascus ruber CGMCC 10910 in submerged fermentation. In this study, H 2 O 2 and dithiothreitol (DTT) were used to change the oxidoreduction potential for investigating the effects of oxidative or reductive substances on Monascus yellow pigment production by Monascus ruber CGMCC 10910. The extracellular ORP could be controlled by H 2 O 2 and DTT. Both cell growth and extracellular water-soluble yellow pigment production were enhanced under H 2 O 2 -induced oxidative (HIO) conditions and were inhibited under dithiothreitol-induced reductive conditions. By optimizing the amount of H 2 O 2 added and the timing of the addition, the yield of extracellular water-soluble yellow pigments significantly increased and reached a maximum of 209 AU, when 10 mM H 2 O 2 was added on the 3rd day of fermentation with M. ruber CGMCC 10910. Under HIO conditions, the ratio of NADH/NAD+ was much lower than that in the control group, and the expression levels of relative pigment biosynthesis genes were up-regulated; moreover, the activity of glucose-6-phosphate dehydrogenase (G6PDH) was increased while 6-phosphofructokinase (PFK) activity was inhibited. Oxidative conditions induced by H 2 O 2 increased water-soluble yellow pigment accumulation via up-regulation of the expression levels of relative genes and by increasing the precursors of pigment biosynthesis through redirection of metabolic flux. In contrast, reductive conditions induced by dithiothreitol inhibited yellow pigment accumulation. This experiment provides a potential strategy for improving the production of Monascus yellow pigments.

Novel mitochondria-targeted heat-soluble proteins identified in the anhydrobiotic Tardigrade improve osmotic tolerance of human cells.

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Sae Tanaka

Full Text Available Tardigrades are able to tolerate almost complete dehydration through transition to a metabolically inactive state, called "anhydrobiosis". Late Embryogenesis Abundant (LEA proteins are heat-soluble proteins involved in the desiccation tolerance of many anhydrobiotic organisms. Tardigrades, Ramazzottius varieornatus, however, express predominantly tardigrade-unique heat-soluble proteins: CAHS (Cytoplasmic Abundant Heat Soluble and SAHS (Secretory Abundant Heat Soluble proteins, which are secreted or localized in most intracellular compartments, except the mitochondria. Although mitochondrial integrity is crucial to ensure cellular survival, protective molecules for mitochondria have remained elusive. Here, we identified two novel mitochondrial heat-soluble proteins, RvLEAM and MAHS (Mitochondrial Abundant Heat Soluble, as potent mitochondrial protectants from Ramazzottius varieornatus. RvLEAM is a group3 LEA protein and immunohistochemistry confirmed its mitochondrial localization in tardigrade cells. MAHS-green fluorescent protein fusion protein localized in human mitochondria and was heat-soluble in vitro, though no sequence similarity with other known proteins was found, and one region was conserved among tardigrades. Furthermore, we demonstrated that RvLEAM protein as well as MAHS protein improved the hyperosmotic tolerance of human cells. The findings of the present study revealed that tardigrade mitochondria contain at least two types of heat-soluble proteins that might have protective roles in water-deficient environments.

Fermentation and complex enzyme hydrolysis for improving the total soluble phenolic contents, flavonoid aglycones contents and bio-activities of guava leaves tea.

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Wang, Lu; Luo, You; Wu, Yanan; Liu, Yan; Wu, Zhenqiang

2018-10-30

There are both soluble and insoluble-bound forms of phenolics in tea-leaf products. In order to increase total soluble phenolics contents, guava leaves tea (GLT) was first fermented with Monascus anka and Saccharomyces cerevisiae, and then hydrolyzed with complex enzymes. The changes in phenolics profiles, antioxidant activities and inhibitory effect on α-glucosidase in processed GLT were investigated. Compared with the un-fermented GLT, fermentation and complex enzymatic processing (FE) significantly increased the total phenolics, total flavonoids, quercetin and kaempferol contents by 2.1, 2.0, 13.0 and 6.8 times, respectively. After the FE, a major proportion of phenolics existed in the soluble form. Quercetin was released in the highest amount among different phenolics. In addition, soluble phenolic extracts from GLT following FE exhibited a highest antioxidant activity and inhibitory effect on α-glucosidase. The paper suggested an improved method for processing GLT into high-value products rich in phenolics and flavonoids aglycones with enhanced health benefits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improving the Carprofen Solubility: Synthesis of the Zn2Al-LDH Hybrid Compound.

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Capsoni, Doretta; Quinzeni, Irene; Bruni, Giovanna; Friuli, Valeria; Maggi, Lauretta; Bini, Marcella

2018-01-01

The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability, and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula [M 2+ 1-x M 3+ x (OH) 2 ](A n- ) x/n yH 2 O (M 2+  = Zn, Mg; M 3+  = Al; A n-  = nitrates, carbonates, chlorides). The possibility to exchange these counterions with drug molecules makes these systems ideal candidates for the drug delivery. In this article, we synthesize by co-precipitation method the hybrid compound Carprofen-Zn 2 Al-LDH. Carprofen, a poorly soluble anti-inflammatory drug, could also benefit of the association with a natural antacid such as LDH, to reduce the gastric irritation after its administration. Through X-ray diffraction and Fourier-transformed infrared spectroscopy (FT-IR), we could verify the effective drug intercalation into LDH. The dissolution tests clearly demonstrate a significant improvement of the drug release rate when carprofen is in the form of hybrid compound. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Nanocrystals of medium soluble actives--novel concept for improved dermal delivery and production strategy.

Science.gov (United States)

Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

2014-08-15

After use in oral pharmaceutical products, nanocrystals are meanwhile applied to improve the dermal penetration of cosmetic actives (e.g. rutin, hesperidin) and of drugs. By now, nanocrystals are only dermally applied made from poorly soluble actives. The novel concept is to formulate nanocrystals also from medium soluble actives, and to apply a dermal formulation containing additionally nanocrystals. The nanocrystals should act as fast dissolving depot, increase saturation solubility and especially accumulate in the hair follicles, to further increase skin penetration. Caffeine was used as model compound with relevance to market products, and a particular process was developed for the production of caffeine nanocrystals to overcome the supersaturation related effect of crystal growth and fiber formation - typical with medium soluble compounds. It is based on low energy milling (pearl milling) in combination with low dielectric constant dispersion media (water-ethanol or ethanol-propylene glycol mixtures) and optimal stabilizers. Most successful was Carbopol(®) 981 (e.g. 20% caffeine in ethanol-propylene glycol 3:7 with 2% Carbopol, w/w). Nanocrystals with varied sizes can now be produced in a controlled process e.g. 660 nm (optimal for hair follicle accumulation) to 250 nm (optimal for fast dissolution). The short term test proved stability over 2 months of the present formulation being sufficient to perform in vivo testing of the novel concept. Copyright © 2014 Elsevier B.V. All rights reserved.

The importance of the accuracy of the experimental data for the prediction of solubility

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SLAVICA ERIĆ

2010-04-01

Full Text Available Aqueous solubility is an important factor influencing several aspects of the pharmacokinetic profile of a drug. Numerous publications present different methodologies for the development of reliable computational models for the prediction of solubility from structure. The quality of such models can be significantly affected by the accuracy of the employed experimental solubility data. In this work, the importance of the accuracy of the experimental solubility data used for model training was investigated. Three data sets were used as training sets – data set 1, containing solubility data collected from various literature sources using a few criteria (n = 319, data set 2, created by substituting 28 values from data set 1 with uniformly determined experimental data from one laboratory (n = 319, and data set 3, created by including 56 additional components, for which the solubility was also determined under uniform conditions in the same laboratory, in the data set 2 (n = 375. The selection of the most significant descriptors was performed by the heuristic method, using one-parameter and multi-parameter analysis. The correlations between the most significant descriptors and solubility were established using multi-linear regression analysis (MLR for all three investigated data sets. Notable differences were observed between the equations corresponding to different data sets, suggesting that models updated with new experimental data need to be additionally optimized. It was successfully shown that the inclusion of uniform experimental data consistently leads to an improvement in the correlation coefficients. These findings contribute to an emerging consensus that improving the reliability of solubility prediction requires the inclusion of many diverse compounds for which solubility was measured under standardized conditions in the data set.

Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion.

Science.gov (United States)

Zhang, Yilan; Luo, Rui; Chen, Yi; Ke, Xue; Hu, Danrong; Han, Miaomiao

2014-06-01

The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

Improved spectrophotometric analysis of fullerenes C60 and C70 in high-solubility organic solvents.

Science.gov (United States)

Törpe, Alexander; Belton, Daniel J

2015-01-01

Fullerenes are among a number of recently discovered carbon allotropes that exhibit unique and versatile properties. The analysis of these materials is of great importance and interest. We present previously unreported spectroscopic data for C60 and C70 fullerenes in high-solubility solvents, including error bounds, so as to allow reliable colorimetric analysis of these materials. The Beer-Lambert-Bouguer law is found to be valid at all wavelengths. The measured data were highly reproducible, and yielded high-precision molar absorbance coefficients for C60 and C70 in o-xylene and o-dichlorobenzene, which both exhibit a high solubility for these fullerenes, and offer the prospect of improved extraction efficiency. A photometric method for a C60/C70 mixture analysis was validated with standard mixtures, and subsequently improved for real samples by correcting for light scattering, using a power-law fit. The method was successfully applied to the analysis of C60/C70 mixtures extracted from fullerene soot.

Preparation of Essential Oil-Based Microemulsions for Improving the Solubility, pH Stability, Photostability, and Skin Permeation of Quercetin.

Science.gov (United States)

Lv, Xia; Liu, Tiantian; Ma, Huipeng; Tian, Yan; Li, Lei; Li, Zhen; Gao, Meng; Zhang, Jianbin; Tang, Zeyao

2017-11-01

Quercetin can bring many benefits to skin based on its various bioactivities. However, the therapeutic effect of quercetin is limited due to the poor water solubility, pH instability, light instability, and skin permeation. The aim of the present work was applying essential oil-based microemulsions to improve the solubility, pH stability, photostability, and skin permeation of quercetin for topical application. Peppermint oil (PO-ME), clove oil (CO-ME), and rosemary oil (RMO-ME) were selected as model essential oils. Microemulsions composed of Cremophor EL/1,2-propanediol/essential oils (47:23:30, w/w) were selected as model formulations, based on the pseudo-ternary phase diagram and the characterizations. In the solubility study, the solubility of quercetin was improved dozens of times by microemulsions. Quercetin was found instable under alkaline condition, with 50% degraded in the solution of pH 13. However, PO-ME, CO-ME, and RMO-ME could protect quercetin from the hydroxide ions, with 47, 9, and 12% of quercetin degraded. In the photostability study, the essential oil-based microemulsions showed the capability of protecting quercetin from degradation under UV radiation. Where more than 67% of quercetin was degraded in aqueous solution, while less than 7% of quercetin degraded in microemulsions. At last, the in vitro skin permeation study showed that the essential oil-based microemulsions could enhance the permeation capacity of quercetin by 2.5-3 times compared to the aqueous solution. Hence, the prepared essential oil microemulsions could improve the solubility, pH stability, photostability, and skin permeation of quercetin, which will be beneficial for its topical application.

Enhancement of Curcumin Solubility by Phase Change from Crystalline to Amorphous in Cur-TPGS Nanosuspension.

Science.gov (United States)

Shin, Gye Hwa; Li, Jinglei; Cho, Jin Hun; Kim, Jun Tae; Park, Hyun Jin

2016-02-01

Nanosuspensions (NSs) were fabricated to enhance water solubility, dissolution rate, and oral adsorption of water insoluble curcumin using sonoprecipitation method. As a good stabilizer, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was used to improve the stability of curcumin-TPGS NSs (Cur-TPGS NSs). Ultrasonic homogenization (UH) could effectively enhance the solubility of curcumin and to produce homogeneous NSs with small particle sizes. Water solubility of curcumin was significantly improved from 0.6 μg/mL in pure water to 260 μg/mL in the mixture of curcumin and TPGS (1:10) with UH treatment. The mean particle size of Cur-TPGS NSs was decreased significantly after UH and maintained between 208 and 246 nm. Lyophilized powder of Cur-TPGS NSs was dissolved about 91.08% whereas the pristine curcumin powder was dissolved only 6.5% at pH 7.4. This study showed a great potential of Cur-TPGS NSs as a good nano-formulation of curcumin with enhanced solubility and improved oral adsorption. © 2016 Institute of Food Technologists®

Effective non-denaturing purification method for improving the solubility of recombinant actin-binding proteins produced by bacterial expression.

Science.gov (United States)

Chung, Jeong Min; Lee, Sangmin; Jung, Hyun Suk

2017-05-01

Bacterial expression is commonly used to produce recombinant and truncated mutant eukaryotic proteins. However, heterologous protein expression may render synthesized proteins insoluble. The conventional method used to express a poorly soluble protein, which involves denaturation and refolding, is time-consuming and inefficient. There are several non-denaturing approaches that can increase the solubility of recombinant proteins that include using different bacterial cell strains, altering the time of induction, lowering the incubation temperature, and employing different detergents for purification. In this study, we compared several non-denaturing protocols to express and purify two insoluble 34 kDa actin-bundling protein mutants. The solubility of the mutant proteins was not affected by any of the approaches except for treatment with the detergent sarkosyl. These results indicate that sarkosyl can effectively improve the solubility of insoluble proteins during bacterial expression. Copyright © 2016. Published by Elsevier Inc.

A Study on Improvement of Solubility of Rofecoxib and its effect on Permeation of Drug from Topical Formulations.

Science.gov (United States)

Kulkarni, Madhur; Nagarsenker, Mangal

2008-01-01

Rofecoxib, a practically insoluble cox-2 selective nonsteroidal antiinflammatory agent was subjected to improvement in solubility by preparing its binary mixtures with beta cyclodextrin using various methods such as physical mixing, co-grinding, kneading with aqueous methanol and co-evaporation from methanol-water mixture. Characterization of the resulting binary mixtures by differential scanning calorimetry and X-ray diffraction studies indicated partial amorphization of the drug in its binary mixtures. In vitro dissolution studies exhibited remarkable increase in rate and extent of dissolution of the drug from its complexes with beta -cyclodextrin. Pure rofecoxib as well as its co-ground binary mixture were formulated as aqueous gels for topical application. In vitro skin permeation of rofecoxib from formulation containing rofecoxib-cyclodextrin complex was significantly higher (p<0.05) at 1, 2, 12, 18 and 24 hr as compared to formulation containing pure rofecoxib. This could be attributed to better solubility of binary mixture in the aqueous gel vehicle leading to greater concentration gradient between the vehicle and skin and hence higher flux of the drug.

Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid proline

DEFF Research Database (Denmark)

Jensen, Katrine Birgitte Tarp; Löbmann, Korbinian; Rades, Thomas

2014-01-01

Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach...... by combining the model drug, naproxen (NAP), with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG) and a second highly soluble amino acid (proline, PRO) for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared...... the molecular interactions in the form of hydrogen bonds between all three components in the mixture. A salt formation between the acidic drug, NAP, and the basic amino acid, ARG, was found in co-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP and NAP–ARG, it could be shown that the highly...

Development of solid dispersion systems of dapivirine to enhance its solubility.

Science.gov (United States)

Gorajana, Adinarayana; Ying, Chan Chiew; Shuang, Yeen; Fong, Pooi; Tan, Zhi; Gupta, Jyoti; Talekar, Meghna; Sharma, Manisha; Garg, Sanjay

2013-06-01

Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.

Uranium solubility and solubility controls in selected Needle's Eye groundwaters

International Nuclear Information System (INIS)

Falck, W.E.; Hooker, P.J.

1991-01-01

The solubility control of uranium in selected groundwater samples from the cliff and sediments at the Needle's Eye natural analogue site is investigated using the speciation code PHREEQE and the CHEMVAL thermodynamic database (release 3). Alkali-earth bearing uranyl carbonate secondary minerals are likely to exert influence on the solubility . Other candidates are UO 2 and arsenates, depending on the prevailing redox conditions. In the absence of literature data, solubility products for important arsenates have been estimated from analogy with other arsenates and phosphates. Phosphates themselves are unlikely to exert control owing to their comparatively high solubilities. The influence of seawater flooding into the sediments is also discussed. The importance of uranyl arsenates in the retardation of uranium in shallow sediments has been demonstrated in theory, but there are some significant gaps in the thermodynamic databases used. (author)

pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

Science.gov (United States)

Wang, Xue-Qing; Zhang, Qiang

2012-10-01

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

Science.gov (United States)

Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

2015-12-07

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

Energy Technology Data Exchange (ETDEWEB)

Fauber, Benjamin P.; René, Olivier; de Leon Boenig, Gladys; Burton, Brenda; Deng, Yuzhong; Eidenschenk, Céline; Everett, Christine; Gobbi, Alberto; Hymowitz, Sarah G.; Johnson, Adam R.; La, Hank; Liimatta, Marya; Lockey, Peter; Norman, Maxine; Ouyang, Wenjun; Wang, Weiru; Wong, Harvey (Genentech); (Argenta)

2014-08-01

Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma–protein unbound fraction and improvements in cellular permeability and aqueous solubility.

A systematic evaluation of solubility enhancing excipients to enable the generation of permeability data for poorly soluble compounds in Caco-2 model.

Science.gov (United States)

Shah, Devang; Paruchury, Sundeep; Matta, Muralikrishna; Chowan, Gajendra; Subramanian, Murali; Saxena, Ajay; Soars, Matthew G; Herbst, John; Haskell, Roy; Marathe, Punit; Mandlekar, Sandhya

2014-01-01

The study presented here identified and utilized a panel of solubility enhancing excipients to enable the generation of flux data in the Human colon carcinoma (Caco-2) system for compounds with poor solubility. Solubility enhancing excipients Dimethyl acetamide (DMA) 1 % v/v, polyethylene glycol (PEG) 400 1% v/v, povidone 1% w/v, poloxamer 188 2.5% w/v and bovine serum albumin (BSA) 4% w/v did not compromise Caco-2 monolayer integrity as assessed by trans-epithelial resistance measurement (TEER) and Lucifer yellow (LY) permeation. Further, these excipients did not affect P-glycoprotein (P-gp) mediated bidirectional transport of digoxin, permeabilities of high (propranolol) or low permeability (atenolol) compounds, and were found to be inert to Breast cancer resistant protein (BCRP) mediated transport of cladribine. This approach was validated further using poorly soluble tool compounds, atazanavir (poloxamer 188 2.5% w/v) and cyclosporine A (BSA 4% w/v) and also applied to new chemical entity (NCE) BMS-A in BSA 4% w/v, for which Caco-2 data could not be generated using the traditional methodology due to poor solubility (solubility of atazanavir by >8 fold whereas BSA 4% w/v increased the solubility of cyclosporine A and BMS-A by >2-4 fold thereby enabling permeability as well as efflux liability estimation in the Caco-2 model with reasonable recovery values. To conclude, addition of excipients such as poloxamer 188 2.5% w/v and BSA 4% w/v to HBSS leads to a significant improvement in the solubility of the poorly soluble compounds resulting in enhanced recoveries without modulating transporter-mediated efflux, expanding the applicability of Caco-2 assays to poorly soluble compounds.

The binding affinity of a soluble TCR-Fc fusion protein is significantly improved by crosslinkage with an anti-C{beta} antibody

Energy Technology Data Exchange (ETDEWEB)

Ozawa, Tatsuhiko; Horii, Masae; Kobayashi, Eiji [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Jin, Aishun [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Department of Immunology, College of Basic Medical Sciences, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081 (China); Kishi, Hiroyuki, E-mail: immkishi@med.u-toyama.ac.jp [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Muraguchi, Atsushi [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

2012-06-01

Highlights: Black-Right-Pointing-Pointer A novel soluble TCR composed of TCR V and C regions with Ig Fc region is generated. Black-Right-Pointing-Pointer TCR-Fc protein immobilized by an anti-C{beta} antibody bound to a p/MHC tetramer. Black-Right-Pointing-Pointer Binding affinity of TCR-Fc was markedly increased by binding with anti-C{beta} antibody. -- Abstract: The identification and cloning of tumor antigen-specific T cell receptors (TCRs) and the production of the soluble form of the TCR (sTCR) contributed to the development of diagnostic and therapeutic tools for cancer. Recently, several groups have reported the development of technologies for the production of sTCRs. The native sTCR has a very low binding affinity for the antigenic peptide/MHC (p/MHC) complex. In this study, we established a technology to produce high affinity, functional sTCRs. We generated a novel sTCR-Fc fusion protein composed of the TCR V and C regions of the TCR linked to the immunoglobulin (Ig) Fc region. A Western blot analysis revealed that the molecular weight of the fusion protein was approximately 60 kDa under reducing conditions and approximately 100-200 kDa under non-reducing conditions. ELISAs using various antibodies showed that the structure of each domain of the TCR-Fc protein was intact. The TCR-Fc protein immobilized by an anti-C{beta} antibody effectively bound to a p/MHC tetramer. An SPR analysis showed that the TCR-Fc protein had a low binding affinity (KD; 1.1 Multiplication-Sign 10{sup -5} M) to the p/MHC monomer. Interestingly, when the TCR-Fc protein was pre-incubated with an anti-C{beta} antibody, its binding affinity for p/MHC increased by 5-fold (2.2 Multiplication-Sign 10{sup -6} M). We demonstrated a novel method for constructing a functional soluble TCR using the Ig Fc region and showed that the binding affinity of the functional sTCR-Fc was markedly increased by an anti-C{beta} antibody, which is probably due to the stabilization of the V

Thermodynamic Approach to Boron Nitride Nanotube Solubility and Dispersion

Science.gov (United States)

Tiano, A. L.; Gibbons, L.; Tsui, M.; Applin, S. I.; Silva, R.; Park, C.; Fay, C. C.

2016-01-01

Inadequate dispersion of nanomaterials is a critical issue that significantly limits the potential properties of nanocomposites and when overcome, will enable further enhancement of material properties. The most common methods used to improve dispersion include surface functionalization, surfactants, polymer wrapping, and sonication. Although these approaches have proven effective, they often achieve dispersion by altering the surface or structure of the nanomaterial and ultimately, their intrinsic properties. Co-solvents are commonly utilized in the polymer, paint, and art conservation industries to selectively dissolve materials. These co-solvents are utilized based on thermodynamic interaction parameters and are chosen so that the original materials are not affected. The same concept was applied to enhance the dispersion of boron nitride nanotubes (BNNTs) to facilitate the fabrication of BNNT nanocomposites. Of the solvents tested, dimethylacetamide (DMAc) exhibited the most stable, uniform dispersion of BNNTs, followed by N,N-dimethylformamide (DMF), acetone, and N-methyl-2-pyrrolidone (NMP). Utilizing the known Hansen solubility parameters of these solvents in comparison to the BNNT dispersion state, a region of good solubility was proposed. This solubility region was used to identify co-solvent systems that led to improved BNNT dispersion in poor solvents such as toluene, hexane, and ethanol. Incorporating the data from the co-solvent studies further refined the proposed solubility region. From this region, the Hansen solubility parameters for BNNTs are thought to lie at the midpoint of the solubility sphere: 16.8, 10.7, and 9.0 MPa(exp 1/2) for delta d, delta p, and delta h, respectively, with a calculated Hildebrand parameter of 21.8 MPa)exp 1/2).

Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

Science.gov (United States)

Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

2016-01-01

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins.

Science.gov (United States)

Abd El Azim, Heba; Nafee, Noha; Ramadan, Alyaa; Khalafallah, Nawal

2015-07-05

This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (∼ 200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2N and residence time of 4.4h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water-soluble vitamins. Copyright © 2015 Elsevier B.V. All rights reserved.

Carboxylated mesoporous carbon microparticles as new approach to improve the oral bioavailability of poorly water-soluble carvedilol.

Science.gov (United States)

Zhang, Yanzhuo; Zhi, Zhizhuang; Li, Xue; Gao, Jian; Song, Yaling

2013-09-15

The main objective of this study was to develop carboxylated ordered mesoporous carbon microparticles (c-MCMs) loaded with a poorly water-soluble drug, intended to be orally administered, able to enhance the drug loading capacity and improve the oral bioavailability. A model drug, carvedilol (CAR), was loaded onto c-MCMs via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The physicochemical properties of the drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and HPLC. It was found that c-MCM has a high drug loading level up to 41.6%, and higher than that of the mesoporous silica template. Incorporation of CAR in both drug carriers enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. After loading CAR into c-MCMs, its oral bioavailability was compared with the marketed product in dogs. The results showed that the bioavailability of CAR was improved 179.3% compared with that of the commercial product when c-MCM was used as the drug carrier. We believe that the present study will help in the design of oral drug delivery systems for enhanced oral bioavailability of poorly water-soluble drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.

Science.gov (United States)

Puolakkainen, Tero; Ma, Hongqian; Kainulainen, Heikki; Pasternack, Arja; Rantalainen, Timo; Ritvos, Olli; Heikinheimo, Kristiina; Hulmi, Juha J; Kiviranta, Riku

2017-01-19

Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.

Influence of milling process on efavirenz solubility

Directory of Open Access Journals (Sweden)

Erizal Zaini

2017-01-01

Full Text Available Introduction: The aim of this study was to investigate the influence of the milling process on the solubility of efavirenz. Materials and Methods: Milling process was done using Nanomilling for 30, 60, and 180 min. Intact and milled efavirenz were characterized by powder X-ray diffraction, scanning electron microscopy (SEM, spectroscopy infrared (IR, differential scanning calorimetry (DSC, and solubility test. Results: The X-ray diffractogram showed a decline on peak intensity of milled efavirenz compared to intact efavirenz. The SEM graph depicted the change from crystalline to amorphous habit after milling process. The IR spectrum showed there was no difference between intact and milled efavirenz. Thermal analysis which performed by DSC showed a reduction on endothermic peak after milling process which related to decreasing of crystallinity. Solubility test of intact and milled efavirenz was conducted in distilled water free CO2with 0.25% sodium lauryl sulfate media and measured using high-performance liquid chromatography method with acetonitrile: distilled water (80:20 as mobile phases. The solubility was significantly increased (P < 0.05 after milling processes, which the intact efavirenz was 27.12 ± 2.05, while the milled efavirenz for 30, 60, and 180 min were 75.53 ± 1.59, 82.34 ± 1.23, and 104.75 ± 0.96 μg/mL, respectively. Conclusions: Based on the results, the solubility of efavirenz improved after milling process.

Natural polymers: Best carriers for improving bioavailability of poorly water soluble drugs in solid dispersions

OpenAIRE

Sandip Sapkal; Mahesh Narkhede; Mukesh Babhulkar; Gautam Mehetre; Ashish Rathi

2013-01-01

ABSTRACTNatural polymers and its modified forms can be used as best alternative for improving bioavailabilityof poorly water soluble drugs in solid dispersion. Most of the natural polymersare hydrophilic and having high swelling capacity. Recent trend towards the use of naturalpolymer demands the replacement of synthetic additives with natural ones. Many plant derivednatural polymers are studied for use in solid dispersion systems, out of which naturalgums, cyclodextrin and carbohydrate are m...

Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives.

Science.gov (United States)

Breda, Susana A; Jimenez-Kairuz, Alvaro F; Manzo, Ruben H; Olivera, María E

2009-04-17

The hydrochlorides of the 1:3 aluminum:norfloxacin and aluminum:ciprofloxacin complexes were characterized according to the Biopharmaceutics Classification System (BCS) premises in comparison with their parent compounds. The pH-solubility profiles of the complexes were experimentally determined at 25 and 37 degrees C in the range of pH 1-8 and compared to that of uncomplexed norfloxacin and ciprofloxacin. Both complexes are clearly more soluble than the antibiotics themselves, even at the lowest solubility pHs. The increase in solubility was ascribed to the species controlling solubility, which were analyzed in the solid phases at equilibrium at selected pHs. Additionally, permeability was set as low, based on data reported in the scientific literature regarding oral bioavailability, intestinal and cell cultures permeabilities and also considering the influence of stoichiometric amounts of aluminum. The complexes fulfill the BCS criterion to be classified as class 3 compounds (high solubility/low permeability). Instead, the active pharmaceutical ingredients (APIs) currently used in solid dosage forms, norfloxacin and ciprofloxacin hydrochloride, proved to be BCS class 4 (low solubility/low permeability). The solubility improvement turns the complexes as potential biowaiver candidates from the scientific point of view and may be a good way for developing more dose-efficient formulations. An immediate release tablet showing very rapid dissolution was obtained. Its dissolution profile was compared to that of the commercial ciprofloxacin hydrochloride tablets allowing to dissolution of the complete dose at a critical pH such as 6.8.

Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs - a case study with valsartan.

Science.gov (United States)

Chella, Naveen; Tadikonda, Ramarao

2015-06-01

Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30 min against the plain drug which showed only 11.31% of drug release in 30 min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher Cmax compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

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Yousaf AM

2016-01-01

Full Text Available Abid Mehmood Yousaf,1,2 Omer Mustapha,1 Dong Wuk Kim,1 Dong Shik Kim,1 Kyeong Soo Kim,1 Sung Giu Jin,1 Chul Soon Yong,3 Yu Seok Youn,4 Yu-Kyoung Oh,5 Jong Oh Kim,3 Han-Gon Choi1 1College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, South Korea; 2Faculty of Pharmacy, University of Central Punjab, Johar, Lahore, Pakistan; 3College of Pharmacy, Yeungnam University, Gyongsan, North Gyeongsang, 4School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi, 5College of Pharmacy, Seoul National University, Seoul, South Korea Purpose: The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate.Methods: Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP and Labrafil® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion.Results: All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1

1,3-disubstituted ureas functionalized with ether groups are potent inhibitors of the soluble epoxide hydrolase with improved pharmacokinetic properties.

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Kim, In-Hae; Tsai, Hsing-Ju; Nishi, Kosuke; Kasagami, Takeo; Morisseau, Christophe; Hammock, Bruce D

2007-10-18

Soluble epoxide hydrolase (sEH) is a therapeutic target for treating hypertension and inflammation. 1,3-Disubstituted ureas functionalized with an ether group are potent sEH inhibitors. However, their relatively low metabolic stability leads to poor pharmacokinetic properties. To improve their bioavailability, we investigated the effect of incorporating various polar groups on the ether function on the inhibition potencies, physical properties, in vitro metabolic stability, and pharmacokinetic properties. The structure-activity relationship studies showed that a hydrophobic linker between the urea group and the ether function is necessary to keep their potency. In addition, urea-ether inhibitors having a polar group such as diethylene glycol or morpholine significantly improved their physical properties and metabolic stability without any loss of inhibitory potency. Furthermore, improved pharmacokinetic properties in murine and canine models were obtained with the resulting inhibitors. These findings will facilitate the usage of sEH inhibitors in animal models of hypertension and inflammation.

Nanosuspension Technology for Solubilizing Poorly Soluble Drugs

OpenAIRE

Deoli Mukesh

2012-01-01

Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. It is estimated that around 40% of drugs in the pipeline cannot be delivered through the preferred route or in some cases, at all owing to poor water solubility. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor1 EL). To date, nanoscale systems f...

Head-To-Head Comparison of Different Solubility-Enabling Formulations of Etoposide and Their Consequent Solubility-Permeability Interplay.

Science.gov (United States)

Beig, Avital; Miller, Jonathan M; Lindley, David; Carr, Robert A; Zocharski, Philip; Agbaria, Riad; Dahan, Arik

2015-09-01

The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility-permeability interplay. The low-solubility anticancer drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility-permeability interplay. All formulations significantly increased etoposide's apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility-permeability tradeoff associated with other formulation techniques. Accounting for the solubility-permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

IMPROVEMENT OF SOLUBILITY OF BADLY WATER SOLUBLE DRUG (IBUPROFEN) BY USING SURFACTANTS AND CARRIERS

OpenAIRE

Md. Zakaria Faruki*, Rishikesh, Elizabeth Razzaque, Mohiuddin Ahmed Bhuiyan

2013-01-01

ABSTRACT: Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of badly water-soluble drugs, their profitable use has been very limited, primarily because of manufacturing difficulties and stability problems. In this study solid solutions of drugs were generally produced by fusion method. The drug along with the excipients (surfactants and carriers) was heated first and then hardened by cooling to room te...

Improving the representation of soluble iron in climate models

Energy Technology Data Exchange (ETDEWEB)

Mahowald, Natalie [Cornell Univ., Ithaca, NY (United States)

2016-11-29

Funding from this grant supported Rachel Sanza, Yan Zhang and partially Samuel Albani. Substantial progress has been made on inclusion of mineralogy, showing the quality of the simulations, and the impact on radiation in the CAM4 and CAM5 (Scanza et al., 2015). In addition, the elemental distribution has been evaluated (and partially supported by this grant) (Zhang et al., 2015), showing that using spatial distributions of mineralogy, improved resperentation of Fe, Ca and Al are possible, compared to the limited available data. A new intermediate complexity soluble iron scheme was implemented in the Bulk Aerosol Model (BAM), which was completed as part of Rachel Scanza’s PhD thesis. Currently Rachel is writing up at least two first author papers describing the general methods and comparison to observations (Scanza et al., in prep.), as well as papers describing the sensitivity to preindustrial conditions and interannual variability. This work lead to the lead PI being asked to write a commentary in Nature (Mahowald, 2013) and two review papers (Mahowald et al., 2014, Mahowald et al., submitted) and contributed to related papers (Albani et al., 2016, Albani et al., 2014, Albani et al., 2015).

Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.

Science.gov (United States)

Fang, Xubin; Fang, Lei; Gou, Shaohua; Cheng, Lin

2013-03-01

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system.

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Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

2012-01-01

Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor(®) EL:Transcutol(®) P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.

Nanoemulsion for improving solubility and permeability of Vitex agnus-castus extract: formulation and in vitro evaluation using PAMPA and Caco-2 approaches.

Science.gov (United States)

Piazzini, Vieri; Monteforte, Elena; Luceri, Cristina; Bigagli, Elisabetta; Bilia, Anna Rita; Bergonzi, Maria Camilla

2017-11-01

The purpose of this study was to develop new formulation for an improved oral delivery of Vitex agnus-castus (VAC) extract. After the optimization and validation of analytical method for quali-quantitative characterization of extract, nanoemulsion (NE) was selected as lipid-based nanocarrier. The composition of extract-loaded NE resulted in triacetin as oil phase, labrasol as surfactant, cremophor EL as co-surfactant and water. NE contains until 60 mg/mL of extract. It was characterized by DLS and TEM analyses and its droplets appear dark with an average diameter of 11.82 ± 0.125 nm and a polydispersity index (PdI) of 0.117 ± 0.019. The aqueous solubility of the extract was improved about 10 times: the extract is completely soluble in the NE at the concentration of 60 mg/mL, while its solubility in water results less than 6 mg. The passive intestinal permeation was tested by using parallel artificial membrane permeation assay (PAMPA) and the permeation across Caco-2 cells after preliminary cytotoxicity studies were also evaluated. NE shows a good solubilizing effect of the constituents of the extract, compared with aqueous solution. The total amount of constituents permeated from NE to acceptor compartment is greater than that permeated from saturated aqueous solution. Caco-2 test confirmed PAMPA results and they revealed that NE was successful in increasing the permeation of VAC extract. This formulation could improve oral bioavailability of extract due to enhanced solubility and permeability of phytocomplex.

Synthesis and Evaluation of Orexin-1 Receptor Antagonists with Improved Solubility and CNS Permeability.

Science.gov (United States)

Perrey, David A; Decker, Ann M; Zhang, Yanan

2018-03-21

Orexins are hypothalamic neuropeptides playing important roles in many functions including the motivation of addictive behaviors. Blockade of the orexin-1 receptor has been suggested as a potential strategy for the treatment of drug addiction. We have previously reported OX 1 receptor antagonists based on the tetrahydroisoquinoline scaffold with excellent OX 1 potency and selectivity; however, these compounds had high lipophilicity (clogP > 5) and low to moderate solubility. In an effort to improve their properties, we have designed and synthesized a series of analogues where the 7-position substituents known to favor OX 1 potency and selectivity were retained, and groups of different nature were introduced at the 1-position where substitution was generally tolerated as demonstrated in previous studies. Compound 44 with lower lipophilicity (clogP = 3.07) displayed excellent OX 1 potency ( K e = 5.7 nM) and selectivity (>1,760-fold over OX 2 ) in calcium mobilization assays. In preliminary ADME studies, 44 showed excellent kinetic solubility (>200 μM), good CNS permeability ( P app = 14.7 × 10 -6 cm/sec in MDCK assay), and low drug efflux (efflux ratio = 3.3).

The solubility-permeability interplay and oral drug formulation design: Two heads are better than one.

Science.gov (United States)

Dahan, Arik; Beig, Avital; Lindley, David; Miller, Jonathan M

2016-06-01

Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility-permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure. Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

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Sonam Choudhary

2017-05-01

Full Text Available Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

[Quantitive variation of polysaccharides and alcohol-soluble extracts in F1 generation of Dendrobium officinale].

Science.gov (United States)

Zhang, Xiao-Ling; Liu, Jing-Jing; Wu, Ling-Shang; Si, Jin-Ping; Guo, Ying-Ying; Yu, Jie; Wang, Lin-Hua

2013-11-01

Using phenol-sulfuric acid method and hot-dip method of alcohol-soluble extracts, the contents of polysaccharides and alcohol-soluble extracts in 11 F1 generations of Dendrobium officinale were determined. The results showed that the polysaccharides contents in samples collected in May and February were 32.89%-43.07% and 25.77%-35.25%, respectively, while the extracts contents were 2.81%-4.85% and 7.90%-17.40%, respectively. They were significantly different among families. The content of polysaccharides in offspring could be significantly improved by hybridization between parents with low and high polysaccharides contents, and the hybrid vigor was obvious. Cross breeding was an effective way for breeding new varieties with higher polysaccharides contents. Harvest time would significantly affect the contents of polysaccharides and alcohol-soluble extracts. The contents of polysaccharides in families collected in May were higher than those of polysaccharides in families collected in February, but the extracts content had the opposite variation. The extents of quantitative variation of polysaccharides and alcohol-soluble extracts were different among families, and each family had its own rules. It would be significant in giving full play to their role as the excellent varieties and increasing effectiveness by studying on the quantitative accumulation regularity of polysaccharides and alcohol-soluble extracts in superior families (varieties) of D. officinale to determine the best harvesting time.

Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility.

Science.gov (United States)

Patel, Shruti V; Patel, Sarsvatkumar

2015-09-18

Self-micro emulsifying drug delivery system (SMEDDS) is one of the methods to improve solubility and bioavailability of poorly soluble drug(s). The knowledge of the solubility of pharmaceuticals in pure lipidic solvents and solvent mixtures is crucial for designing the SMEDDS of poorly soluble drug substances. Since, experiments are very time consuming, a model, which allows for solubility predictions in solvent mixtures based on less experimental data is desirable for efficiency. Solvents employed were Labrafil® M1944CS and Labrasol® as lipidic solvents; Capryol-90®, Capryol-PGMC® and Tween®-80 as surfactants; Transcutol® and PEG-400 as co-solvents. Solubilities of both drugs were determined in single solvent systems at temperature (T) range of 283-333K. In present study, we investigated the applicability of the thermodynamic model to understand the solubility behavior of drugs in the lipiodic solvents. By using the Van't Hoff and general solubility theory, the thermodynamic functions like Gibbs free energy, enthalpy and entropy of solution, mixing and solvation for drug in single and mixed solvents were understood. The thermodynamic parameters were understood in the framework of drug-solvent interaction based on their chemical similarity and dissimilarity. Clotrimazole and Fluconazole were used as active ingredients whose solubility was measured in single solvent as a function of temperature and the data obtained were used to derive mathematical models which can predict solubility in multi-component solvent mixtures. Model dependent parameters for each drug were calculated at each temperature. The experimental solubility data of solute in mixed solvent system were measured experimentally and further correlated with the calculates values obtained from exponent model and log-linear model of Yalkowsky. The good correlation was observed between experimental solubility and predicted solubility. Copyright © 2015 Elsevier B.V. All rights reserved.

Solubilities of uranium for TILA-99

International Nuclear Information System (INIS)

Ollila, K.; Ahonen, L.

1998-11-01

This report presents the evaluation of the uranium solubilities in the reference waters of TILA-99. The behaviour of uranium has been discussed separately in the near-field and far-field conditions. The bentonite/groundwater interactions have been considered in the compositions of the fresh and saline near-field reference waters. The far-field groundwaters' compositions include fresh, brackish, saline and very saline, almost brine-type compositions. The pH and redox conditions, as the main parameters affecting the solubilities, are considered. A literature study was made in order to obtain information on the recent dissolution and leaching experiments of UO 2 and spent fuel. The latest literature includes studies on UO 2 solubility under anoxic conditions, in which the methods for simulating the reducing conditions of deep groundwater have been improved. Studies on natural uraninite and its alteration products give a valuable insight into the long-term behaviour of spent fuel. Also the solubility equilibria for some relevant poorly known uranium minerals have been determined. The solubilities of the selected solubility-limiting phases were calculated using the geochemical code, EQ3/6. The NEA database for uranium was the basis for the modelling. The recently extended and updated SR '97 database was used for comparison. The solubility products for uranophane were taken from the latest literature. The recommended values for solubilities were given after a comparison between the calculated solubilities, experimental information and measured concentrations in natural groundwaters. The experiments include several UO 2 dissolution studies in synthetic groundwaters with compositions close to the reference groundwaters. (author)

Solubilities of uranium for TILA-99

Energy Technology Data Exchange (ETDEWEB)

Ollila, K. [VTT Chemical Technology, Espoo (Finland); Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

1998-11-01

This report presents the evaluation of the uranium solubilities in the reference waters of TILA-99. The behaviour of uranium has been discussed separately in the near-field and far-field conditions. The bentonite/groundwater interactions have been considered in the compositions of the fresh and saline near-field reference waters. The far-field groundwaters` compositions include fresh, brackish, saline and very saline, almost brine-type compositions. The pH and redox conditions, as the main parameters affecting the solubilities, are considered. A literature study was made in order to obtain information on the recent dissolution and leaching experiments of UO{sub 2} and spent fuel. The latest literature includes studies on UO{sub 2} solubility under anoxic conditions, in which the methods for simulating the reducing conditions of deep groundwater have been improved. Studies on natural uraninite and its alteration products give a valuable insight into the long-term behaviour of spent fuel. Also the solubility equilibria for some relevant poorly known uranium minerals have been determined. The solubilities of the selected solubility-limiting phases were calculated using the geochemical code, EQ3/6. The NEA database for uranium was the basis for the modelling. The recently extended and updated SR `97 database was used for comparison. The solubility products for uranophane were taken from the latest literature. The recommended values for solubilities were given after a comparison between the calculated solubilities, experimental information and measured concentrations in natural groundwaters. The experiments include several UO{sub 2} dissolution studies in synthetic groundwaters with compositions close to the reference groundwaters. (author) 81 refs.

The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

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Sean Shaw

2009-12-01

Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

Cocrystals of Hydrochlorothiazide: Solubility and Diffusion/Permeability Enhancements through Drug-Coformer Interactions.

Science.gov (United States)

Sanphui, Palash; Devi, V Kusum; Clara, Deepa; Malviya, Nidhi; Ganguly, Somnath; Desiraju, Gautam R

2015-05-04

Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multicomponent crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4-aminobenzoic acid (PABA), succinamide (SAM), and resorcinol (RES) were prepared using liquid-assisted grinding, and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane permeability were studied using a Franz diffusion cell. Except for the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All of the cocrystals showed improved diffusion/membrane permeability compared to that of HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case of PABA, NCT, and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux. This cocrystal contains a primary sulfonamide dimer synthon similar to that of HCT polymorphs, which may be a reason for its unusual behavior. Hirshfeld surface analysis was carried out in all cases to determine whether a correlation exists between cocrystal permeability and drug-coformer interactions.

Formulation of poorly water-soluble Gemfibrozil applying power ultrasound.

Science.gov (United States)

Ambrus, R; Naghipour Amirzadi, N; Aigner, Z; Szabó-Révész, P

2012-03-01

The dissolution properties of a drug and its release from the dosage form have a basic impact on its bioavailability. Solubility problems are a major challenge for the pharmaceutical industry as concerns the development of new pharmaceutical products. Formulation problems may possibly be overcome by modification of particle size and morphology. The application of power ultrasound is a novel possibility in drug formulation. This article reports on solvent diffusion and melt emulsification, as new methods supplemented with drying in the field of sonocrystallization of poorly water-soluble Gemfibrozil. During thermoanalytical characterization, a modified structure was detected. The specific surface area of the drug was increased following particle size reduction and the poor wettability properties could also be improved. The dissolution rate was therefore significantly increased. Copyright © 2011 Elsevier B.V. All rights reserved.

Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies

International Nuclear Information System (INIS)

Zhou Pei; Wagner, Gerhard

2010-01-01

Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs.

SORPTION AND SOLUBILITY OF LOW-SHRINKAGE RESIN-BASED DENTAL COMPOSITES

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Sevda Yantcheva

2016-04-01

Full Text Available Background: Resin-based composites are well-established restorative materials. However, these materials may absorb significant amounts of water when exposed to aqueous environments. Sorption and solubility are affecting composite restorations by two different mechanisms; the first is the up taking of water producing an increased weight and the second is the dissolution of materials in water, leading to a weight reduction of the final conditioned samples. Objective: To measure the water sorption and solubility of different low-shrinkage resin-based composites. Six materials were selected: Filtek P60, Filtek Ultimate, SonicFill, Filtek Silorane, Kalore and Venus Diamond. Materials and methods: Five disc specimens were prepared of each material and polymerized with diode light-curing unit. Water sorption and solubility of the different materials were were calculated by means of weighting the samples before and after water immersion and desiccation. Data were statistically analyzed using Shapiro-Wilk One Way Analysis of Variance followed by the Holm-Sidak comparison test . Results: There were significant differences (p<=0.001 between materials regarding sorption and solubility. Regarding sorption F. Silorane showed lowest values, followed by SonicFill, without significant difference between them. Statistical significant differences exist between F. Silorane and F.P60, F. Ultimate, Kalore. Significant differences exist between SonicFill and F. Ultimate. F.Silorane (-0.018 and Kalore (-0.010 showed lowest values of solubility but there were marginal difference among all composites investigated. Conclusions: 1.The material with lowest values of sorption and solubility was F.Silorane. 2. The attained sorption and solubility values for composites are influenced by the differences in resin matrix composition and filler contend. 3. Modifications of dimethacrylate matrix did not minimize significantly sorption and solubility of composites. 4. Besides water

Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

Science.gov (United States)

Ozeki, Tetsuya; Tagami, Tatsuaki

2013-01-01

The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

Enhancing production and cytotoxic activity of polymeric soluble FasL-based chimeric proteins by concomitant expression of soluble FasL.

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Aurore Morello

Full Text Available Membrane FasL is the natural trigger of Fas-mediated apoptosis. A soluble homotrimeric counterpart (sFasL also exists which is very weakly active, and needs oligomerization beyond its trimeric state to induce apoptosis. We recently generated a soluble FasL chimera by fusing the immunoglobulin-like domain of the leukemia inhibitory factor receptor gp190 to the extracellular region of human FasL, which enabled spontaneous dodecameric homotypic polymerization of FasL. This polymeric soluble human FasL (pFasL displayed anti-tumoral activity in vitro and in vivo without systemic cytotoxicity in mouse. In the present work, we focused on the improvement of pFasL, with two complementary objectives. First, we developed more complex pFasL-based chimeras that contained a cell-targeting module. Secondly, we attempted to improve the production and/or the specific activity of pFasL and of the cell-targeting chimeras. We designed two chimeras by fusing to pFasL the extracellular portions of the HLA-A2 molecule or of a human gamma-delta TCR, and analyzed the consequences of co-expressing these molecules or pFasL together with sFasL on their heterotopic cell production. This strategy significantly enhanced the production of pFasL and of the two chimeras, as well as the cytotoxic activity of the two chimeras but not of pFasL. These results provide the proof of concept for an optimization of FasL-based chimeric proteins for a therapeutic use.

Improved Extraction and Quality Characterization of Water-Soluble Polysaccharide from Gamma-Irradiated Lentinus edodes.

Science.gov (United States)

Akram, Kashif; Shahbaz, Hafiz Muhammad; Kim, Gui-Ran; Farooq, Umar; Kwon, Joong-Ho

2017-02-01

Gamma irradiation was applied to the improved extraction of water-soluble polysaccharides (WSPs) from dried Lentinus edodes. Irradiation provided a dose-dependent increase in extraction yield (0 kGy, 2.01%; 7.5 kGy, 4.03%; 15 kGy, 7.17%) and purity (0 kGy, 78.8%; 7.5 kGy, 83.1%; 15 kGy, 85.6%) of the WSPs from hot-water extraction. The effect of irradiation was evident in the degraded microstructures and reduced molecular weights of the WSPs. However, nuclear magnetic resonance, Fourier-transform infrared, and X-ray diffraction spectroscopic analyses provided comparable structures of WSPs from nonirradiated and irradiated samples. UV-visible spectra showed a dose-dependent decline in intensity, but an improvement in thermal properties of the WSPs from the irradiated mushroom samples was observed. © 2017 Institute of Food Technologists®.

Ionic liquid-assisted solublization for improved enzymatic esterification of phenolic acids

DEFF Research Database (Denmark)

Yang, Zhiyong; Guo, Zheng; Xu, Xuebing

2012-01-01

in a binary system, which is composed of ionic liquid tOMA•TFA (trioctylmethylammonium Trifluoroacetate) and octanol. Ionic liquid tOMA•TFA has great solubility towards most of phenolic acid. The strategy of increasing the solubility of phenolic in ionic liquid tOMA•TFA was proved to be an efficient way...... for increasing conversion of phenolic acids. The mixture ratio between tOMA•TFA and octanol was varied from 1:4 to 1:16 (v/v), it was found that the highest conversion of dihydrocaffeic acid (DHCA) was achieved when tOMA•TFA and octanol was mixed as 1:12 (v/v). It was also found that conversion of DHCA at 70 o...

Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative.

Science.gov (United States)

Bitsch, R; Wolf, M; Möller, J; Heuzeroth, L; Grüneklee, D

1991-01-01

The bioequivalence of thiamin in 2 therapeutically used preparations was tested in 10 healthy young men. Thiamin was orally administered either as lipophilic benfotiamine or as water-soluble thiamin mononitrate. Biokinetic data, measured as area under the curve and maximal concentration in plasma and hemolysate after ingestion, demonstrated a significantly improved bioavailability from the lipophilic derivative despite an ingested dose of only 40% as compared with the water-soluble salt. A superior cellular efficacy of benfotiamine was also concluded from the short-term stimulation of the thiamin-dependent transketolase activity in erythrocytes.

Serum Soluble Corin is Decreased in Stroke.

Science.gov (United States)

Peng, Hao; Zhu, Fangfang; Shi, Jijun; Han, Xiujie; Zhou, Dan; Liu, Yan; Zhi, Zhongwen; Zhang, Fuding; Shen, Yun; Ma, Juanjuan; Song, Yulin; Hu, Weidong

2015-07-01

Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke. © 2015 American Heart Association, Inc.

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate.

Science.gov (United States)

Yousaf, Abid Mehmood; Mustapha, Omer; Kim, Dong Wuk; Kim, Dong Shik; Kim, Kyeong Soo; Jin, Sung Giu; Yong, Chul Soon; Youn, Yu Seok; Oh, Yu-Kyoung; Kim, Jong Oh; Choi, Han-Gon

2016-01-01

The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil(®) M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of water-soluble fenofibrate.

Incorporation of Mg and Ca into nanostructured Fe2O3 improves Fe solubility in dilute acid and sensory characteristics in foods.

Science.gov (United States)

Hilty, Florentine M; Knijnenburg, Jesper T N; Teleki, Alexandra; Krumeich, Frank; Hurrell, Richard F; Pratsinis, Sotiris E; Zimmermann, Michael B

2011-01-01

Iron deficiency is one of the most common micronutrient deficiencies worldwide. Food fortification can be an effective and sustainable strategy to reduce Fe deficiency but selection of iron fortificants remains a challenge. Water-soluble compounds, for example, FeSO(4), usually demonstrate high bioavailability but they often cause unacceptable sensory changes in foods. On the other hand, poorly acid-soluble Fe compounds, for example FePO(4), may cause fewer adverse sensory changes in foods but are usually not well bioavailable since they need to be dissolved in the stomach prior to absorption. The solubility and the bioavailability of poorly acid-soluble Fe compounds can be improved by decreasing their primary particle size and thereby increasing their specific surface area. Here, Fe oxide-based nanostructured compounds with added Mg or Ca were produced by scalable flame aerosol technology. The compounds were characterized by nitrogen adsorption, X-ray diffraction, transmission electron microscopy, and Fe solubility in dilute acid. Sensory properties of the Fe-based compounds were tested in 2 highly reactive, polyphenol-rich food matrices: chocolate milk and fruit yoghurt. The Fe solubility of nanostructured Fe(2)O(3) doped with Mg or Ca was higher than that of pure Fe(2)O(3). Since good solubility in dilute acid was obtained despite the inhomogeneity of the powders, inexpensive precursors, for example Fe- and Ca-nitrates, can be used for their manufacture. Adding Mg or Ca lightened powder color, while sensory changes when added to foods were less pronounced than for FeSO(4). The combination of high Fe solubility and low reactivity in foods makes these flame-made nanostructured compounds promising for food fortification. Practical Application: The nanostructured iron-containing compounds presented here may prove useful for iron fortification of certain foods; they are highly soluble in dilute acid and likely to be well absorbed in the gut but cause less severe

In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin-epichlorohydrin polymers.

Science.gov (United States)

Nie, Shufang; Zhang, Shu; Pan, Weisan; Liu, Yanli

2011-05-01

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin-epichlorohydrin polymer (β-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with β-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A(L), which indicated the formation of 1:1 complex between glipizide and β-CDP. β-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-β-CD. The dissolution rate of drug from the β-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/β-CDP systems was higher than that from the corresponding ones with HP-β-CD, which indicated that β-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide /β-CDP inclusion complex after oral administration to beagle dogs.

Poly(glycolide multi-arm star polymers: Improved solubility via limited arm length

Directory of Open Access Journals (Sweden)

Florian K. Wolf

2010-06-01

Full Text Available Due to the low solubility of poly(glycolic acid (PGA, its use is generally limited to the synthesis of random copolyesters with other hydroxy acids, such as lactic acid, or to applications that permit direct processing from the polymer melt. Insolubility is generally observed for PGA when the degree of polymerization exceeds 20. Here we present a strategy that allows the preparation of PGA-based multi-arm structures which significantly exceed the molecular weight of processable oligomeric linear PGA (<1000 g/mol. This was achieved by the use of a multifunctional hyperbranched polyglycerol (PG macroinitiator and the tin(II-2-ethylhexanoate catalyzed ring-opening polymerization of glycolide in the melt. With this strategy it is possible to combine high molecular weight with good molecular weight control (up to 16,000 g/mol, PDI = 1.4–1.7, resulting in PGA multi-arm star block copolymers containing more than 90 wt % GA. The successful linkage of PGA arms and PG core via this core first/grafting from strategy was confirmed by detailed NMR and SEC characterization. Various PG/glycolide ratios were employed to vary the length of the PGA arms. Besides fluorinated solvents, the materials were soluble in DMF and DMSO up to an average arm length of 12 glycolic acid units. Reduction in the Tg and the melting temperature compared to the homopolymer PGA should lead to simplified processing conditions. The findings contribute to broadening the range of biomedical applications of PGA.

Plutonium solubilities

International Nuclear Information System (INIS)

Puigdomnech, I.; Bruno, J.

1991-02-01

Thermochemical data has been selected for plutonium oxide, hydroxide, carbonate and phosphate equilibria. Equilibrium constants have been evaluated in the temperature range 0 to 300 degrees C at a pressure of 1 bar to T≤100 degrees C and at the steam saturated pressure at higher temperatures. Measured solubilities of plutonium that are reported in the literature for laboratory experiments have been collected. Solubility data on oxides, hydroxides, carbonates and phosphates have been selected. No solubility data were found at temperatures higher than 60 degrees C. The literature solubility data have been compared with plutonium solubilities calculated with the EQ3/6 geochemical modelling programs, using the selected thermodynamic data for plutonium. (authors)

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

Science.gov (United States)

Ramprasath, Vanu R; Jenkins, David J A; Lamarche, Benoit; Kendall, Cyril W C; Faulkner, Dorothea; Cermakova, Luba; Couture, Patrick; Ireland, Chris; Abdulnour, Shahad; Patel, Darshna; Bashyam, Balachandran; Srichaikul, Korbua; de Souza, Russell J; Vidgen, Edward; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W; Frohlich, Jiri; Jones, Peter J H

2014-10-18

Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction

Chemical analysis of simulated high level waste glasses to support stage III sulfate solubility modeling

Energy Technology Data Exchange (ETDEWEB)

Fox, K. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-03-17

The U.S. Department of Energy (DOE), Office of Environmental Management (EM) is sponsoring an international, collaborative project to develop a fundamental model for sulfate solubility in nuclear waste glass. The solubility of sulfate has a significant impact on the achievable waste loading for nuclear waste forms within the DOE complex. These wastes can contain relatively high concentrations of sulfate, which has low solubility in borosilicate glass. This is a significant issue for low-activity waste (LAW) glass and is projected to have a major impact on the Hanford Tank Waste Treatment and Immobilization Plant (WTP). Sulfate solubility has also been a limiting factor for recent high level waste (HLW) sludge processed at the Savannah River Site (SRS) Defense Waste Processing Facility (DWPF). The low solubility of sulfate in glass, along with melter and off-gas corrosion constraints, dictate that the waste be blended with lower sulfate concentration waste sources or washed to remove sulfate prior to vitrification. The development of enhanced borosilicate glass compositions with improved sulfate solubility will allow for higher waste loadings and accelerate mission completion.The objective of the current scope being pursued by SHU is to mature the sulfate solubility model to the point where it can be used to guide glass composition development for DWPF and WTP, allowing for enhanced waste loadings and waste throughput at these facilities. A series of targeted glass compositions was selected to resolve data gaps in the model and is identified as Stage III. SHU fabricated these glasses and sent samples to SRNL for chemical composition analysis. SHU will use the resulting data to enhance the sulfate solubility model and resolve any deficiencies. In this report, SRNL provides chemical analyses for the Stage III, simulated HLW glasses fabricated by SHU in support of the sulfate solubility model development.

Improving the de-agglomeration and dissolution of a poorly water soluble drug by decreasing the agglomerate strength of the cohesive powder.

Science.gov (United States)

Allahham, Ayman; Stewart, Peter J; Das, Shyamal C

2013-11-30

Influence of ternary, poorly water-soluble components on the agglomerate strength of cohesive indomethacin mixtures during dissolution was studied to explore the relationship between agglomerate strength and extent of de-agglomeration and dissolution of indomethacin (Ind). Dissolution profiles of Ind from 20% Ind-lactose binary mixtures, and ternary mixtures containing additional dibasic calcium phosphate (1% or 10%; DCP), calcium sulphate (10%) and talc (10%) were determined. Agglomerate strength distributions were estimated by Monte Carlo simulation of particle size, work of cohesion and packing fraction distributions. The agglomerate strength of Ind decreased from 1.19 MPa for the binary Ind mixture to 0.84 MPa for 1DCP:20Ind mixture and to 0.42 MPa for 1DCP:2Ind mixture. Both extent of de-agglomeration, demonstrated by the concentration of the dispersed indomethacin distribution, and extent of dispersion, demonstrated by the particle size of the dispersed indomethacin, were in descending order of 1DCP:2Ind>1DCP:20Ind>binary Ind. The addition of calcium sulphate dihydrate and talc also reduced the agglomerate strength and improved de-agglomeration and dispersion of indomethacin. While not definitively causal, the improved de-agglomeration and dispersion of a poorly water soluble drug by poorly water soluble components was related to the agglomerate strength of the cohesive matrix during dissolution. Copyright © 2013 Elsevier B.V. All rights reserved.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

Directory of Open Access Journals (Sweden)

Chen ZQ

2012-02-01

Full Text Available Zhi-Qiang Chen, Ying Liu, Ji-Hui Zhao, Lan Wang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaBackground: Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS was developed to improve the oral bioavailability of indirubin.Methods: A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats.Results: The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor® EL:Transcutol® P (15:40:45, w/w/w. Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS.Conclusion: The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.Keywords: supersaturatable self-microemulsifying drug delivery system, indirubin, bioavailability, oral drug delivery, hydrophilic polymer

Pure Phase Solubility Limits: LANL

International Nuclear Information System (INIS)

C. Stockman

2001-01-01

The natural and engineered system at Yucca Mountain (YM) defines the site-specific conditions under which one must determine to what extent the engineered and the natural geochemical barriers will prevent the release of radioactive material from the repository. Most important mechanisms for retention or enhancement of radionuclide transport include precipitation or co-precipitation of radionuclide-bearing solid phases (solubility limits), complexation in solution, sorption onto surfaces, colloid formation, and diffusion. There may be many scenarios that could affect the near-field environment, creating chemical conditions more aggressive than the conditions presented by the unperturbed system (such as pH changes beyond the range of 6 to 9 or significant changes in the ionic strength of infiltrated waters). For an extended period of time, the near-field water composition may be quite different and more extreme in pH, ionic strength, and CO 2 partial pressure (or carbonate concentration) than waters at some distance from the repository. Reducing conditions, high pH (up to 11), and low carbonate concentration may be present in the near-field after reaction of infiltrating groundwater with engineered barrier systems, such as cementitious materials. In the far-field, conditions are controlled by the rock-mass buffer providing a near-neutral, oxidizing, low-ionic-strength environment that controls radionuclide solubility limits and sorption capacities. There is the need for characterization of variable chemical conditions that affect solubility, speciation, and sorption reactions. Modeling of the groundwater chemistry is required and leads to an understanding of solubility and speciation of the important radionuclides. Because experimental studies cannot be performed under the numerous potential chemical conditions, solubility limitations must rely on geochemical modeling of the radionuclide's chemistry. Fundamental thermodynamic properties, such as solubility products

Pure Phase Solubility Limits: LANL

Energy Technology Data Exchange (ETDEWEB)

C. Stockman

2001-01-26

The natural and engineered system at Yucca Mountain (YM) defines the site-specific conditions under which one must determine to what extent the engineered and the natural geochemical barriers will prevent the release of radioactive material from the repository. Most important mechanisms for retention or enhancement of radionuclide transport include precipitation or co-precipitation of radionuclide-bearing solid phases (solubility limits), complexation in solution, sorption onto surfaces, colloid formation, and diffusion. There may be many scenarios that could affect the near-field environment, creating chemical conditions more aggressive than the conditions presented by the unperturbed system (such as pH changes beyond the range of 6 to 9 or significant changes in the ionic strength of infiltrated waters). For an extended period of time, the near-field water composition may be quite different and more extreme in pH, ionic strength, and CO{sub 2} partial pressure (or carbonate concentration) than waters at some distance from the repository. Reducing conditions, high pH (up to 11), and low carbonate concentration may be present in the near-field after reaction of infiltrating groundwater with engineered barrier systems, such as cementitious materials. In the far-field, conditions are controlled by the rock-mass buffer providing a near-neutral, oxidizing, low-ionic-strength environment that controls radionuclide solubility limits and sorption capacities. There is the need for characterization of variable chemical conditions that affect solubility, speciation, and sorption reactions. Modeling of the groundwater chemistry is required and leads to an understanding of solubility and speciation of the important radionuclides. Because experimental studies cannot be performed under the numerous potential chemical conditions, solubility limitations must rely on geochemical modeling of the radionuclide's chemistry. Fundamental thermodynamic properties, such as solubility

Clinical significance of detecting soluble glycocalicin and thrombopoietin in the differential diagnosis of idiopathic thrombocytopenic purpura and aplstic anemia

International Nuclear Information System (INIS)

Zhao Yiming; He Yang; Xu Haiyan; Ruan Changgeng

2010-01-01

Objective: To investigate the clinical significance of detecting soluble platelet glycocalicin (sGC) and thrombopoietin (TPO) in the differential diagnosis of idiopathic thrombocytopenic purpura (ITP) and aplastic anemia (AA). Methods: Plasma sGC and serum TPO in 83 patients with ITP, 47 patients with AA and 50 normal individuals were detected by iminunoradiometric assay (IRMA) and enzymelinked immunosorbent assay (ELISA), respectively. Statistical analysis was performed using Q test and P value of 0.05). But serum TPO level in AA group was significantly higher than that in ITP and normal groups: (857.43 ± 228.43) ng/L vs (90.32 ± 39.43) ng/L and (70.29 ± 25.16) ng/L, and they were considered statistically significant (Q=24.45 and 18.25, both P < 0.01). Conclusion: Detecting plasma sGC and serum TPO might be helpful for differentiating ITP and AA and for understanding the pathophysiology of thrombocytopenia. (authors)

The solubility of palladium(II) bis-dimethylglyoximate

International Nuclear Information System (INIS)

Maghzian, R.

1978-01-01

The solubility of palladium(II) bis-dimethylglyoximate in different solutions has been determined. Values obtained for the solubility of the palladium complex are tabulated. The solubility is the lowest in water, ammonium acetate and a 25% acetone-water mixture. It is highest in dilute HCl and acetone but precipitation from aqueous acetone should be satisfactory for most purposes if the acetone content of the solvent is roughly less than 50% by volume. The solubility in dilute HCl reflects the concern by previous workers for losses in precipitation from mineral acid. In general, however, the losses are unlikely to be significant unless the quantity of palladium to be precipitated and weighed is small. (T.G.)

Soluble and stable zethrenebis(dicarboximide) and its quinone

KAUST Repository

Sun, Zhe

2010-10-15

Soluble and stable zethrenebis(dicarboximide) (1) was synthesized by an in situ Stille cross coupling/transannular cyclization reaction. 1 showed largely improved photostability and solubility compared with the very unstable zethrene and it also exhibited far-red absorption and emission with high photoluminescence quantum yield. Bromination of 1 with NBS/DMF gave its quinone form 2 via an unusual pathway. © 2010 American Chemical Society.

Quantifying solubility enhancement due to particle size reduction and crystal habit modification: case study of acetyl salicylic acid.

Science.gov (United States)

Hammond, Robert B; Pencheva, Klimentina; Roberts, Kevin J; Auffret, Tony

2007-08-01

The poor solubility of potential drug molecules is a significant problem in the design of pharmaceutical formulations. It is well known, however, that the solubility of crystalline materials is enhanced when the particle size is reduced to submicron levels and this factor can be expected to enhance drug product bioavailability. Direct estimation of solubility enhancement, as calculated via the Gibbs-Thompson relationship, demands reasonably accurate values for the particle/solution interfacial tension and, in particular, its anisotropy with respect to the crystal product's habit and morphology. In this article, an improved, more molecule-centered, approach is presented towards the calculation of solubility enhancement factors in which molecular modeling techniques are applied, and the effects associated with both crystal habit modification and solvent choice are examined. A case study for facetted, acetyl salicylic acid (aspirin) crystals in equilibrium with saturated aqueous ethanol solution reveals that their solubility will be enhanced in the range (7-58%) for a crystal size of 0.02 microm, with significantly higher enhancement for crystal morphologies in which the hydrophobic crystal faces are more predominant than the hydrophilic faces and for solvents in which the solubility is smaller. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Poly(3-hydroxybutyrate) and Eudragit E microparticles: a release system to enhance the aqueous solubility of felodipine and simvastatin

International Nuclear Information System (INIS)

Bazzo, Giovana C.; Pezzini, Bianca R.; Zetola, Melissa; Wagner, Theodoro M.; Caetano, Daniela B.; Boch, Maura; Schmucker, Iara C.; Schucko, Sacha K.

2009-01-01

Poor water-soluble drugs are a problem for the development of oral solid dosage forms, since it has great potential for low bioavailability. Thus, release systems that promote the increase of aqueous solubility of these drugs are advantageous. This study aimed to evaluate the feasibility of incorporation of felodipine and simvastatin in polymeric microparticles, to improve the aqueous solubility of the drugs. Microparticles of poly(3-hydroxybutyrate) [PHB] and Eudragit E was prepared by emulsion - solvent evaporation technique and characterized as to morphology and encapsulation efficiency of the drugs. Particles with spherical shapes and high levels of drug encapsulated were obtained. There was a significant increase in aqueous solubility of felodipine and simvastatin after its incorporation into the polymeric microparticles. X-ray diffraction analysis showed the conversion of both drugs to amorphous form, which may have contributed to increased the solubility. (author)

Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO2(cr)

International Nuclear Information System (INIS)

Rai, Dhanpat; Kitamura, Akira; Rosso, Kevin M.; Sasaki, Takayuki; Kobayashi, Taishi

2016-01-01

Solubility studies were conducted with HfO 2 (cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg -1 . These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO 2 (am) suspensions to 90 C to ascertain whether the HfO 2 (am) converts to HfO 2 (cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO 2 (cr) contains a small fraction of less crystalline, but not amorphous, material [HfO 2 (lcr)] and this, rather than the HfO 2 (cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log 10 K 0 values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO 2 (lcr)[HfO 2 (lcr) + 2H 2 O ↔ Hf 4+ + 4OH - ]. The log 10 of the solubility product of HfO 2 (cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.

Science.gov (United States)

Brownfoot, Fiona C; Hastie, Roxanne; Hannan, Natalie J; Cannon, Ping; Tuohey, Laura; Parry, Laura J; Senadheera, Sevvandi; Illanes, Sebastian E; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

2016-03-01

explant-conditioned media (to whole vessels). Finally, we examined the effects of metformin on angiogenesis on maternal omental vessel explants. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary endothelial cells, villous cytotrophoblast cells, and preterm preeclamptic placental villous explants. The reduction in soluble fms-like tyrosine kinase 1 and soluble endoglin secretion was rescued by coadministration of succinate, which suggests that the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin were likely to be regulated at the level of the mitochondria. In addition, the mitochondrial electron transport chain inhibitors rotenone and antimycin reduced soluble fms-like tyrosine kinase 1 secretion, which further suggests that soluble fms-like tyrosine kinase 1 secretion is regulated through the mitochondria. Mitochondrial electron transport chain activity in preterm preeclamptic placentas was increased compared with gestation-matched control subjects. Metformin improved features of endothelial dysfunction relevant to preeclampsia. It reduced endothelial cell messenger RNA expression of vascular cell adhesion molecule 1 that was induced by tumor necrosis factor-α (vascular cell adhesion molecule 1 is an inflammatory adhesion molecule up-regulated with endothelial dysfunction and is increased in preeclampsia). Placental conditioned media impaired bradykinin-induced vasodilation; this effect was reversed by metformin. Metformin also improved whole blood vessel angiogenesis impaired by fms-like tyrosine kinase 1. Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain. The activity of the mitochondrial electron transport chain was increased in preterm preeclamptic placenta. Metformin reduced endothelial dysfunction, enhanced vasodilation in omental arteries, and induced

Improving the Representation of Soluble Iron in Climate Models

Energy Technology Data Exchange (ETDEWEB)

Perez Garcia-Pando, Carlos [Columbia Univ., New York, NY (United States)

2016-03-13

Mineral dust produced in the arid and semi-arid regions of the world is the dominant source of iron (Fe) in atmospheric aerosol inputs to the open ocean. The bioavailable Fe fraction of atmospheric dust is thought to regulate and occasionally limit the primary productivity in large oceanic regions, which influences the CO2 uptake from the atmosphere affecting the Earth’s climate. Because Fe bioavailability cannot be directly measured, it is assumed that the dissolved Fe or highly reactive Fe in the dust is bioavailable. The fraction of soluble Fe in dust is mainly controlled by: (1) the mineral composition of the soils and the emitted dust from the source areas; (2) the atmospheric processing that converts the Fe in Fe-bearing minerals into highly soluble forms of Fe. The project has mainly focused on constraining the mineral composition of dust aerosols (1), a previously neglected, yet a key issue to constrain the deposition of soluble iron. Deriving aerosol mineral composition requires global knowledge of the soil mineral content, which is available from poorly constrained global atlases. In addition, the mineral content of the emitted aerosol differs from that of the parent soil. Measurements of soil mineral fractions are based upon wet sedimentation (or ’wet sieving’) techniques that disturb the soil sample, breaking aggregates that are found in the original, undispersed soil that is subject to wind erosion. Wet sieving alters the soil size distribution, replacing aggregates that are potentially mobilized as aerosols with a collection of smaller particles. A major challenge is to derive the size-distributed mineral fractions of the emitted dust based upon their fractions measured from wet-sieved soils. Finally, representations of dust mineral composition need to account for mixtures of minerals. Examination of individual particles shows that iron, an element that is central to many climate processes, is often found as trace impurities of iron oxide

Measuring Compartment Size and Gas Solubility in Marine Mammals

Science.gov (United States)

2015-09-30

bends? Effect of diving behaviour and physiology on modelled gas exchange for three species: Ziphius cavirostris, Mesoplodon densirostris and Hyperoodon...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Measuring Compartment Size and Gas Solubility in Marine...is to develop methods to estimate marine mamal tissue compartment sizes, and tissue gas solubility. We aim to improve the data available for the

Nanonization strategies for poorly water-soluble drugs.

Science.gov (United States)

Chen, Huabing; Khemtong, Chalermchai; Yang, Xiangliang; Chang, Xueling; Gao, Jinming

2011-04-01

Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor(®) EL). In this review, several major nanonization techniques that seek to overcome these limitations for drug solubilization are presented. Strategies including drug nanocrystals, nanoemulsions and polymeric micelles are reviewed. Finally, perspectives on existing challenges and future opportunities are highlighted. Published by Elsevier Ltd.

Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol.

Science.gov (United States)

Zoghbi, Abdelmoumin; Geng, Tianjiao; Wang, Bo

2017-11-01

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.

Hydrogen solubility in FLiNaK mixed with titanium powder

International Nuclear Information System (INIS)

Yagi, Juro; Sagara, Akio; Watanabe, Takashi; Tanaka, Teruya; Takayama, Sadatsugu; Muroga, Takeo

2015-01-01

Highlights: • The hydrogen solubility in a FLiNaK mixed with Ti powder was investigated. • A significant increase in hydrogen solubility was observed. • Controlling the purity of the molten salt was found to be one of the key issues. • A vanadium alloy would be compatible with the Ti powder/molten salt mixture. - Abstract: The hydrogen solubility in a FLiNaK molten salt mixed with Ti powder was investigated. A hydrogen-soluble metal powder mixed with a molten salt can increase the effective hydrogen solubility of the molten salt, which is currently a major disadvantage of molten salts. A significant increase in hydrogen solubility was observed, even with a mass fraction of Ti powder of only 0.1 wt%. The increase of hydrogen solubility was so large that a vanadium alloy would be compatible with the Ti powder/molten salt mixture, unlike typical molten salts that result in an unacceptably large tritium inventory in the vanadium alloy. In addition, contamination of the Ti powder by oxidation suppressed the hydrogen uptake and release capability. Controlling the purity of the molten salt was found to be one of the key issues for the metal powder mixture concept.

Curcumin-Zn(II) complex for enhanced solubility and stability: an approach for improved delivery and pharmacodynamic effects.

Science.gov (United States)

Sareen, Rashmi; Jain, Nitin; Dhar, K L

2016-08-01

The aim of present investigation was to prepare Curcumin-Zn(II) complex in a view to enhance solubility, stability and pharmacodynamic effect in experimentally induced ulcerative colitis. Curcumin-Zn(II) complex was prepared by stirring curcumin with anhydrous zinc chloride at a molar ratio of 1:1. The prepared curcumin metallocomplex was characterized by TLC, FTIR, UV spectroscopy and (1)H NMR. In vitro kinetic degradation and solubility of Curcumin and Curcumin-Zn(II) complex was analyzed spectrophotometrically. Pharmacodynamic evaluation of curcumin and its metal complex was assessed in ulcerative colitis in mice. Curcumin showed chelation with zinc ion as confirmed by the TLC, FTIR, UV spectroscopy and (1)H NMR. The results of TLC [Rf value], IR Spectroscopy [shifting of stretching vibrations of υ(C=C) and υ(C=O)], UV spectra [deconvoluted with absorption band at 432-466.4 nm] of Curcumin-Zn(II) complex compared to curcumin confirmed the formation of metallocomplex. (1)HNMR spectra of Curcumin-Zn(II) showed the upfield shift of Ha and Hb. Kinetic stability studies showed metallocomplex with zinc exhibited good stability. In vivo study revealed significant reduction in severity and extent of colonic damage with Curcumin-Zn(II) which were further confirmed by histopathological study. This study recognizes higher solubility and stability of Curcumin-Zn(II) complex and suggested better pharmacodynamic effects.

Resveratrol cocrystals with enhanced solubility and tabletability.

Science.gov (United States)

Zhou, Zhengzheng; Li, Wanying; Sun, Wei-Jhe; Lu, Tongbu; Tong, Henry H Y; Sun, Changquan Calvin; Zheng, Ying

2016-07-25

Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased serum soluble corin in dyslipidemia: A cross-sectional study.

Science.gov (United States)

Wang, Xiaolei; Chen, Shi; Zhang, Qiu; Liu, Yan; Liu, Lu; Li, Huiling; Peng, Hao

2015-10-23

Natriuretic peptides have been associated with dyslipidemia. As a physiological activator of natriuretic peptides, corin might also be associated with dyslipidemia. However, this association has not yet been studied in Chinese populations. Serum soluble corin and blood lipid profiles were determined for 2496 participants aged above 30y. A logistic regression model was applied to evaluate the association between serum soluble corin and dyslipidemia. Serum soluble corin was significantly increased in participants with dyslipidemia in both men (Pdyslipidemia positively increased with increasing levels of serum soluble corin in men (P for trend=0.011) and women (P for trend=0.043). Participants with a high corin level were more likely to have dyslipidemia than those with a low corin level in men (OR, 95% CI: 1.45, 1.07-1.97) and women (OR, 95% CI: 1.33, 1.04-1.70). Serum soluble corin was significantly and positively associated with dyslipidemia. Our findings suggested that serum soluble corin may be a marker or risk factor for dyslipidemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Issues concerning the determination of solubility products of sparingly soluble crystalline solids. Solubility of HfO{sub 2}(cr)

Energy Technology Data Exchange (ETDEWEB)

Rai, Dhanpat [Rai Enviro-Chem, LLC, Yachats, OR (United States); Kitamura, Akira [Japan Atomic Energy Agency, Ibaraki (Japan); Rosso, Kevin M. [Pacific Northwest National Laboratory, Richland, WA (United States); Sasaki, Takayuki; Kobayashi, Taishi [Kyoto Univ. (Japan)

2016-11-01

Solubility studies were conducted with HfO{sub 2}(cr) solid as a function HCl and ionic strength ranging from 2.0 to 0.004 mol kg{sup -1}. These studies involved (1) using two different amounts of the solid phase, (2) acid washing the bulk solid phase, (3) preheating the solid phase to 1400 C, and (4) heating amorphous HfO{sub 2}(am) suspensions to 90 C to ascertain whether the HfO{sub 2}(am) converts to HfO{sub 2}(cr) and to determine the solubility from the oversaturation direction. Based on the results of these treatments it is concluded that the HfO{sub 2}(cr) contains a small fraction of less crystalline, but not amorphous, material [HfO{sub 2}(lcr)] and this, rather than the HfO{sub 2}(cr), is the solubility-controlling phase in the range of experimental variables investigated in this study. The solubility data are interpreted using both the Pitzer and SIT models and they provide log{sub 10} K{sup 0} values of -(59.75±0.35) and -(59.48±0.41), respectively, for the solubility product of HfO{sub 2}(lcr)[HfO{sub 2}(lcr) + 2H{sub 2}O ↔ Hf{sup 4+} + 4OH{sup -}]. The log{sub 10} of the solubility product of HfO{sub 2}(cr) is estimated to be < -63. The observation of a small fraction of less crystalline higher solubility material is consistent with the general picture that mineral surfaces are often structurally and/or compositionally imperfect leading to a higher solubility than the bulk crystalline solid. This study stresses the urgent need, during interpretation of solubility data, of taking precautions to make certain that the observed solubility behavior for sparingly-soluble solids is assigned to the proper solid phase.

Improvement of aqueous solubility and rectal absorption of 6-mercaptopurine by addition of sodium benzoate.

Science.gov (United States)

Takeichi, Y; Kimura, T

1994-10-01

The solubility of 6-mercaptopurine (6-MP) in water increased as the concentration of sodium benzoate or sodium hippurate in the solution increased. The solubility of 6-MP in 20% (w/v) sodium benzoate or sodium hippurate solution was about 6-fold larger than that of 6-MP alone. The stability constant of the soluble complex of 6-MP with sodium benzoate was estimated to be 2-8 M-1 from (1) phase-solubility study and (2) analysis of chemical shifts observed in 1H-NMR. Partition of 6-MP from the saturated solution to n-octanol was also greatly increased by the addition of sodium benzoate or sodium hippurate, the degree being less in the latter. Administration of 6-MP with 20% (w/v) sodium benzoate to rat rectum resulted in enhanced absorption and the area under the plasma concentration-time curve was comparable to that obtained by intravenous administration (bioavailability = 100%), while the bioavailability after intrarectal administration of 6-MP with 20% (w/v) sodium hippurate was only 9%. The reason for the difference was discussed.

Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution.

Science.gov (United States)

Dash, Rajendra Narayan; Mohammed, Habibuddin; Humaira, Touseef; Ramesh, Devi

2015-10-01

A solid self-nanoemulsifying drug-delivery system (solid SNEDDS) has been explored to improve the solubility and dissolution profile of glipizide. SNEDDS preconcentrate was systematically optimized using a circumscribed central composite design by varying Captex 355 (Oil), Solutol HS15 (Surfactant) and Imwitor 988 (Co-surfactant). The optimized SNEDDS preconcentrate consisted of Captex 355 (30% w/w), Solutol HS15 (45% w/w) and Imwitor 988 (25% w/w). The saturation solubility (SS) of glipizide in optimized SNEDDS preconcentrate was found to be 45.12 ± 1.36 mg/ml, indicating an improvement (1367 times) of glipizide solubility as compared to its aqueous solubility (0.033 ± 0.0021 mg/ml). At 90% SS, glipizide was loaded to the optimized SNEDDS. In-vitro dilution of liquid SNEDDS resulted in a nanoemulsion with a mean droplet size of 29.4 nm. TEM studies of diluted liquid SNEDDS confirmed the uniform shape and size of the globules. The liquid SNEDDS was adsorbed onto calcium carbonate and talc to form solid SNEDDS. PXRD, DSC, and SEM results indicated that, the presence of glipizide as an amorphous and as a molecular dispersion state within solid SNEDDS. Glipizide dissolution improved significantly (p < 0.001) from the solid SNEDDS (∼100% in 15 min) as compared to the pure drug (18.37%) and commercial product (65.82) respectively.

A theoretical and experimental study on solubility of curatives in rubbers

NARCIS (Netherlands)

Guo, R.; Talma, Auke; Datta, Rabin; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

2009-01-01

The current study provides indications for improving the properties of dissimilar rubber blends. As solubility is a key factor for the distribution and a driving force for the migration of curatives in dissimilar rubber blends, it is of importance to have precise data of their solubilities. The

Improvement of dissolution behavior of poorly water soluble drugs by biodegradable polymeric submicron carriers containing sparingly methylated β-cyclodextrin.

Science.gov (United States)

Singhavi, Dilesh J; Khan, Shagufta; Yeole, Pramod G

2013-04-01

The objective of this study was to develop submicron carriers of two drugs that are practically insoluble in water, i.e. meloxicam and aceclofenac, to improve their dissolution behavior. The phase solubility of the drugs was studied using different concentrations of sparingly methylated β-cyclodextrin, Kleptose(®) Crysmeβ (Crysmeb), in the presence and absence of 0.2 % w/v water-soluble chitosan. Drug-loaded submicron particles (SMPs) were prepared using chitosan chlorhydrate and Crysmeb by the ionotropic gelation method. The SMPs were characterized in terms of powder X-ray diffraction, Fourier transforms infrared spectroscopy, size determination, process yield, drug loading, encapsulation efficiency, surface morphology and in vitro release. The drug loading in the SMPs was enhanced in the presence of Crysmeb. The in vitro drug release was found to be enhanced with SMPs prepared using higher concentrations of Crysmeb. These results indicate that SMPs formed from chitosan chlorhydrate and Crysmeb are promising submicron carriers for enhancing the dissolution of meloxicam and aceclofenac.

Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction.

Science.gov (United States)

Lee, Jung-Mi; Park, Kyung-Mi; Lim, Soo-Jeong; Lee, Mi-Kyung; Kim, Chong-Kook

2002-01-01

Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics.

Gas solubilities widespread applications

CERN Document Server

Gerrard, William

1980-01-01

Gas Solubilities: Widespread Applications discusses several topics concerning the various applications of gas solubilities. The first chapter of the book reviews Henr's law, while the second chapter covers the effect of temperature on gas solubility. The third chapter discusses the various gases used by Horiuti, and the following chapters evaluate the data on sulfur dioxide, chlorine data, and solubility data for hydrogen sulfide. Chapter 7 concerns itself with solubility of radon, thoron, and actinon. Chapter 8 tackles the solubilities of diborane and the gaseous hydrides of groups IV, V, and

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

Directory of Open Access Journals (Sweden)

Bhaskar Daravath

2018-05-01

Full Text Available ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05 in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%. The mean dissolution time (MDT was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min. indicating faster drug release. The DE (% dissolution efficiency was increased by 2.5 folds (61.63% compared to conventional tablets (23.71%. From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

Directory of Open Access Journals (Sweden)

Sandra Geschka

Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

Solubility of hydrogen isotopes in liquid LiPb

International Nuclear Information System (INIS)

Konishi, S.; Yamamoto, Y.; Noborio, K.; Calderoni, P.; Merrill, B.

2014-01-01

This research was performed mainly in the first half of the task 1-2 of TITAN project to investigate the interaction between hydrogen isotopes and liquid LiPb. Solubility of hydrogen in liquid LiPb was measured under a static condition. Kyoto University provided the first experimental apparatus shipped to Idaho, and Kyushu University succeeded the experiment and further improved. Obtained solubility generally agreed with some previous reports, but varied orders of magnitudes suggesting influence of impurity or other chemical processes. (author)

1,3-Disubstituted Ureas Functionalized with Ether Groups are Potent Inhibitors of the Soluble Epoxide Hydrolase with Improved Pharmacokinetic Properties

OpenAIRE

Kim, In-Hae; Tsai, Hsing-Ju; Nishi, Kosuke; Kasagami, Takeo; Morisseau, Christophe; Hammock, Bruce D.

2007-01-01

Soluble epoxide hydrolase (sEH) is a therapeutic target for treating hypertension and inflammation. 1,3-Disubstituted ureas functionalized with an ether group are potent sEH inhibitors. However, their relatively low metabolic stability leads to poor pharmacokinetic properties. To improve their bioavailability, we investigated the effect of incorporating various polar groups on the ether function on the inhibition potencies, physical properties, in vitro metabolic stability, and pharmacokineti...

Fullerene solubility-current density relationship in polymer solar cells

International Nuclear Information System (INIS)

Renz, Joachim A.; Gobsch, Gerhard; Hoppe, Harald; Troshin, Pavel A.; Razumov, V.F.

2008-01-01

During the last decade polymer solar cells have undergone a steady increase in overall device efficiency. To date, essential efficiency improvements of polymer-fullerene solar cells require the development of new materials. Whilst most research efforts aim at an improved or spectrally extended absorption of the donor polymer, not so much attention has been paid to the fullerene properties themselves. We have investigated a number of structurally related fullerenes, in order to study the relationship between chemical structure and resulting polymer-fullerene bulk heterojunction photovoltaic properties. Our study reveals a clear connection between the fullerene solubility as material property on one hand and the solar cells short circuit photocurrent on the other hand. The tendency of the less soluble fullerene derivates to aggregate was accounted for smaller current densities in the respective solar cells. Once a minimum solubility of approx. 25 mg/ml in chlorobenzene was overcome by the fullerene derivative, the short circuit current density reached a plateau, of about 8-10 mA/cm 2 . Thus the solubility of the fullerene derivative directly influences the blend morphology and displays an important parameter for efficient polymer-fullerene bulk heterojunction solar cell operation. (copyright 2008 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (Abstract Copyright [2008], Wiley Periodicals, Inc.)

Modulation of solubility and dissolution of furosemide by preparation of phospholipid complex

Directory of Open Access Journals (Sweden)

Mona Semalty

2014-01-01

Full Text Available Aim: The aim of this study is to improve the solubility and dissolution of furosemide (a potent high ceiling diuretic used for the treatment of hypertension and a Class IV drug that is low solubility and low permeability drug as per the Biopharmaceutical Classification System by preparing its phospholipid complexes or pharmacosomes. Materials and Methods: Furosemide was complexed with phosphatidylcholine in four different molar ratios (1:1, 1:2, 1:3 and 1:4 by conventional solvent-evaporation technique. The pharmacosomes prepared were evaluated for drug content, solubility, X-ray powder diffraction (XRPD and in-vitro dissolution study. Results: Pharmacosomes of furosemide showed high drug content ranging from 88.30% to 100%. XRPD studies confirmed the formation of phospholipid complex and the amorphization of drug in the complex. The water solubility was found to be increased up to six-fold in the complexes. The octanol solubility also increased in the complexes indicating the probable increase in permeability. The in-vitro dissolution profile of the prepared complexes was found to be much better than furosemide. Conclusion: It was concluded that the phospholipid complexes can be effectively used for improving the solubility, dissolution, permeability and hence the bioavailability of furosemide like Class IV drugs.

Impact of bleaching agents on water sorption and solubility of resin luting cements.

Science.gov (United States)

Torabi Ardakani, Mahshid; Atashkar, Berivan; Bagheri, Rafat; Burrow, Michael F

2017-08-01

The aim of the present study was to evaluate the effect of distilled water and home and office bleaching agents on the sorption and solubility of resin luting cements. A total of 18 disc-shaped specimens were prepared from each of four resin cements: G-CEM LinkAce, Panavia F, Rely X Unicem, and seT. Specimens were cured according to the manufacturers' instructions and randomly divided into three groups of six, where they were treated with either an office or home bleaching agent or immersed in distilled water (control). Water sorption and solubility were measured by weighing the specimens before and after immersion and desiccation. Data were analyzed using Pearson correlation coefficient, two-way analysis of variance (ANOVA) and Tukey's test. There was a significant, positive correlation between sorption and solubility. Two-way anova showed significant differences among all resin cements tested for either sorption or solubility. Water sorption and solubility of all cements were affected significantly by office bleaching, and even more by home bleaching agents. Sorption and solubility behavior of the studied cements were highly correlated and significantly affected by applying either office or home bleaching agents; seT showed the highest sorption and solubility, whereas Rely X Unicem revealed the lowest. © 2016 John Wiley & Sons Australia, Ltd.

Active intestinal drug absorption and the solubility-permeability interplay.

Science.gov (United States)

Porat, Daniel; Dahan, Arik

2018-02-15

The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

Science.gov (United States)

Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

2012-11-01

A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

Revised thermodynamic properties of brucite determined by solubility studies and its significance to nuclear waste isolation

International Nuclear Information System (INIS)

Xiong, Yongliang

2007-01-01

MgO is the only engineered barrier certified by EPA for the Waste Isolation Pilot Plant (WIPP) in USA. The German Asse repository will also employ an Mg(OH) 2 (brucite)-based engineered barrier. The chemical function of the engineered barrier is to consume CO 2 that may be generated by the microbial degradation of organic materials in waste packages. Experimental results at SNL indicate that MgO is first hydrated as brucite, and then brucite is carbonated as hydromagnesite (5424) (Mg 5 (CO 3 ) 4 (OH) 2 · 4H 2 O). As MgO is in excess relative to CO 2 that may be produced, the brucite-hydromagnesite (5424) assemblage would buffer f CO2 in the repository. Consequently, the thermodynamic properties of this assemblage is of great significance to the performance assessment (PA) as actinide solubility is strongly affected by f CO2 . In turn, PA is important to the demonstration of the long-term safety of nuclear waste repositories, as assessed by the use of probabilistic performance calculations. There is a substantial discrepancy for Δ f G brucite 0 in recent publications, ranging from -830.4 (Harvie et al., 1984; Geochim. Cosmochim. Acta, 723-751), through -831.9 (Brown et al., 1996; J. Chem. Soc., Dalton Trans., 3071-3075), through -833.5 (Robie and Hemingway, 1995; USGS Bull., 2131), and to -835.9 kJ mol -1 (Konigsberger et al., 1999; Geochim. Cosmochim. Acta, 3105-3119). Using the Δ f G hydromagnesite (5424) 0 from Konigsberger et al., the predicted log f CO2 for this assemblage would range from -5.96 (Δ f G brucite 0 from Harvie et al.) to -4.84 (Δ f G brucite 0 from Konigsberger et al.). Therefore, it is desirable to better constrain the Δ f G brucite 0 . For this reason, a series of solubility experiments involving brucite in NaCl solutions ranging from 0.01 M to 4.0 M have being conducted at SNL. The derived Δ f G brucite 0 from this study by extrapolation to infinite dilution via Pitzer formalism is -830.8 kJ mol -1 , which is in excellent agreement with

Revisiting Hansen Solubility Parameters by Including Thermodynamics

NARCIS (Netherlands)

Louwerse, Manuel J; Fernández-Maldonado, Ana María; Rousseau, Simon; Moreau-Masselon, Chloe; Roux, Bernard; Rothenberg, Gadi

2017-01-01

The Hansen solubility parameter approach is revisited by implementing the thermodynamics of dissolution and mixing. Hansen's pragmatic approach has earned its spurs in predicting solvents for polymer solutions, but for molecular solutes improvements are needed. By going into the details of entropy

Significant improvement of thermal stability of glucose 1-dehydrogenase by introducing disulfide bonds at the tetramer interface.

Science.gov (United States)

Ding, Haitao; Gao, Fen; Liu, Danfeng; Li, Zeli; Xu, Xiaohong; Wu, Min; Zhao, Yuhua

2013-12-10

Rational design was applied to glucose 1-dehydrogenase (LsGDH) from Lysinibacillus sphaericus G10 to improve its thermal stability by introduction of disulfide bridges between subunits. One out of the eleven mutants, designated as DS255, displayed significantly enhanced thermal stability with considerable soluble expression and high specific activity. It was extremely stable at pH ranging from 4.5 to 10.5, as it retained nearly 100% activity after incubating at different buffers for 1h. Mutant DS255 also exhibited high thermostability, having a half-life of 9900min at 50°C, which was 1868-fold as that of its wild type. Moreover, both of the increased free energy of denaturation and decreased entropy of denaturation of DS255 suggested that the enzyme structure was stabilized by the engineered disulfide bonds. On account of its robust stability, mutant DS255 would be a competitive candidate in practical applications of chiral chemicals synthesis, biofuel cells and glucose biosensors. Copyright © 2013 Elsevier Inc. All rights reserved.

Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt.

Science.gov (United States)

Sanphui, Palash; Tothadi, Srinu; Ganguly, Somnath; Desiraju, Gautam R

2013-12-02

Sildenafil is a drug used to treat erectile dysfunction and pulmonary arterial hypertension. Because of poor aqueous solubility of the drug, the citrate salt, with improved solubility and pharmacokinetics, has been marketed. However, the citrate salt requires an hour to reach its peak plasma concentration. Thus, to improve solubility and bioavailability characteristics, cocrystals and salts of the drug have been prepared by treating aliphatic dicarboxylic acids with sildenafil; the N-methylated piperazine of the drug molecule interacts with the carboxyl group of the acid to form a heterosynthon. Salts are formed with oxalic and fumaric acid; salt monoanions are formed with succinic and glutaric acid. Sildenafil forms cocrystals with longer chain dicarboxylic acids such as adipic, pimelic, suberic, and sebacic acids. Auxiliary stabilization via C-H···O interactions is also present in these cocrystals and salts. Solubility experiments of sildenafil cocrystal/salts were carried out in 0.1N HCl aqueous medium and compared with the solubility of the citrate salt. The glutarate salt and pimelic acid cocrystal dissolve faster than the citrate salt in a two hour dissolution experiment. The glutarate salt exhibits improved solubility (3.2-fold) compared to the citrate salt in water. Solubilities of the binary salts follow an inverse correlation with their melting points, while the solubilities of the cocrystals follow solubilities of the coformer. Pharmacokinetic studies on rats showed that the glutarate salt exhibits doubled plasma AUC values in a single dose within an hour compared to the citrate salt. The high solubility of glutaric acid, in part originating from the strained conformation of the molecule and its high permeability, may be the reason for higher plasma levels of the drug.

Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

Directory of Open Access Journals (Sweden)

Hadjira Rabti

2014-06-01

Full Text Available Elementary osmotic pump (EOP is a unique extended release (ER drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ, a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA, respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30 and sodium lauryl sulfate (SLS. The plasticizer amount and molecular weight (MW together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.

Impact of Conventional and Integrated Management Systems on the Water-Soluble Vitamin Content in Potatoes, Field Beans, and Cereals.

Science.gov (United States)

Freitag, Sabine; Verrall, Susan R; Pont, Simon D A; McRae, Diane; Sungurtas, Julia A; Palau, Raphaëlle; Hawes, Cathy; Alexander, Colin J; Allwood, J William; Foito, Alexandre; Stewart, Derek; Shepherd, Louise V T

2018-01-31

The reduction of the environmental footprint of crop production without compromising crop yield and their nutritional value is a key goal for improving the sustainability of agriculture. In 2009, the Balruddery Farm Platform was established at The James Hutton Institute as a long-term experimental platform for cross-disciplinary research of crops using two agricultural ecosystems. Crops representative of UK agriculture were grown under conventional and integrated management systems and analyzed for their water-soluble vitamin content. Integrated management, when compared with the conventional system, had only minor effects on water-soluble vitamin content, where significantly higher differences were seen for the conventional management practice on the levels of thiamine in field beans (p water-soluble vitamin content of the crops analyzed here.

The thermal Z-isomerization-induced change in solubility and physical properties of (all-E)-lycopene.

Science.gov (United States)

Murakami, Kazuya; Honda, Masaki; Takemura, Ryota; Fukaya, Tetsuya; Kubota, Mitsuhiro; Wahyudiono; Kanda, Hideki; Goto, Motonobu

2017-09-16

The effect of Z-isomerization of (all-E)-lycopene on its solubility in organic solvents and physical properties was investigated. Lycopene samples containing different Z-isomer contents (23.8%, 46.9%, and 75.6% of total lycopene) were prepared from high-purity (all-E)-lycopene by thermal Z-isomerization in dichloromethane (CH 2 Cl 2 ). As the Z-isomer content increased, the relative solubility of lycopene significantly improved. Although (all-E)-lycopene barely dissolved in ethanol (0.6 mg/L), the solubilities of lycopene containing 23.8%, 46.9%, and 75.6% Z-isomers were 484.5, 914.7, and 2401.7 mg/L, respectively. Furthermore, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses clearly indicated that (all-E)-lycopene was present in the crystal state, while Z-isomers of lycopene were present in amorphous states. A number of studies have suggested that Z-isomers of lycopene are better absorbed in the human body than the all-E-isomer. This may be due to the change in solubility and physical properties of lycopene by the Z-isomerization. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro solubility of calcium, iron and zinc in relation to phytic acid levels in rice-based consumer products in China.

Science.gov (United States)

Liang, Jianfen; Han, Bei-Zhong; Nout, M J Robert; Hamer, Robert J

2010-02-01

In vitro solubility of calcium, iron and zinc in relation to phytic acid (PA) levels in 30 commercial rice-based foods from China was studied. Solubility of minerals and molar ratios of PA to minerals varied with degrees of processing. In primary products, [PA]/[Ca] values were less than 5 and [PA]/[Fe] and [PA]/[Zn] similarly ranged between 5 and 74, with most values between 20 and 30. [PA]/[mineral] molar ratios in intensively processed products were lower. Solubility of calcium ranged from 0% to 87%, with the lowest in brown rice (12%) and the highest in infant foods (50%). Iron solubility in two-thirds of samples was lower than 30%, and that of zinc narrowly ranged from 6% to 30%. Solubility of minerals was not significantly affected by [PA]/[mineral]. At present, neither primary nor intensively processed rice-based products are good dietary sources of minerals. Improvements should be attempted by dephytinization, mineral fortification or, preferably, combination of both.

Neptunium (IV) oxalate solubility

International Nuclear Information System (INIS)

Luerkens, D.W.

1983-07-01

The equilibrium solubility of neptunium (IV) oxalate in nitric/oxalic acid solutions was determined at 22 0 C, 45 0 C, and 60 0 C. The concentrations of nitric/oxalic acid solutions represented a wide range of free oxalate ion concentration. A mathematical solubility model was developed which is based on the formation of the known complexes of neptunium (IV) oxalate. the solubility model uses a simplified concentration parameter which is proportional to the free oxalate ion concentration. The solubility model can be used to estimate the equilibrium solubility of neptunium (IV) oxalate over a wide range of oxalic and nitric acid concentrations at each temperature

Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.

Science.gov (United States)

Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergström, Christel A S

2013-03-28

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Science.gov (United States)

Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

2007-01-01

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Total and soluble oxalate content of some Indian spices.

Science.gov (United States)

Ghosh Das, Sumana; Savage, G P

2012-06-01

Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.

Biochemical characterization of soluble proteins in pecan [Carya illinoinensis (Wangenh.) K. Koch].

Science.gov (United States)

Venkatachalam, Mahesh; Roux, Kenneth H; Sathe, Shridhar K

2008-09-10

Pecans (cv. Desirable) contained approximately 10% protein on a dry weight basis. The minimum nitrogen solubility (5.9-7.5%) at 0.25-0.75 M trichloroacetic acid represented the nonprotein nitrogen. Among the solvents assessed for protein solubilization, 0.1 M NaOH was the most effective, while borate saline buffer (pH 8.45) was judged to be optimal for protein solubilization. The protein solubility was minimal in the pH range of 3-7 and significantly increased on either side of this pH range. Increasing the NaCl concentration from 0 to 4 M significantly improved ( approximately 8-fold increase) protein solubilization. Following Osborne protein fractionation, the alkali-soluble glutelin fraction (60.1%) accounted for a major portion of pecan proteins followed by globulin (31.5%), prolamin (3.4%), and albumin (1.5%), respectively. The majority of pecan polypeptides were in the molecular mass range of 12-66 kDa and in the pI range of 4.0-8.3. The pecan globulin fraction was characterized by the presence of several glycoprotein polypeptides. Lysine was the first limiting essential amino acid in the defatted flour, globulin, prolamin, and alkaline glutelin fractions. Leucine and tryptophan were the first limiting essential amino acids in albumin and acid glutelin fractions, respectively. Rabbit polyclonal antibodies detected a range of pecan polypeptides in the 12-60 kDa range, of which the globulin fraction contained the most reactive polypeptides.

Hydrogen solubility measurements of analyzed tall oil fractions and a solubility model

International Nuclear Information System (INIS)

Uusi-Kyyny, Petri; Pakkanen, Minna; Linnekoski, Juha; Alopaeus, Ville

2017-01-01

Highlights: • Hydrogen solubility was measured in four tall oil fractions between 373 and 597 K. • Continuous flow synthetic isothermal and isobaric method was used. • A Henry’s law model was developed for the distilled tall oil fractions. • The complex composition of the samples was analyzed and is presented. - Abstract: Knowledge of hydrogen solubility in tall oil fractions is important for designing hydrotreatment processes of these complex nonedible biobased materials. Unfortunately measurements of hydrogen solubility into these fractions are missing in the literature. This work reports hydrogen solubility measured in four tall oil fractions between 373 and 597 K and at pressures from 5 to 10 MPa. Three of the fractions were distilled tall oil fractions their resin acids contents are respectively 2, 20 and 23 in mass-%. Additionally one fraction was a crude tall oil (CTO) sample containing sterols as the main neutral fraction. Measurements were performed using a continuous flow synthetic isothermal and isobaric method based on the visual observation of the bubble point. Composition of the flow was changed step-wise for the bubble point composition determination. We assume that the tall oil fractions did not react during measurements, based on the composition analysis performed before and after the measurements. Additionally the densities of the fractions were measured at atmospheric pressure from 293.15 to 323.15 K. A Henry’s law model was developed for the distilled tall oil fractions describing the solubility with an absolute average deviation of 2.1%. Inputs of the solubility model are temperature, total pressure and the density of the oil at 323.15 K. The solubility of hydrogen in the CTO sample can be described with the developed model with an absolute average deviation of 3.4%. The solubility of hydrogen increases both with increasing pressure and/or increasing temperature. The more dense fractions of the tall oil exhibit lower hydrogen

Molecular Design of Soluble Biopolyimide with High Rigidity

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Sumant Dwivedi

2018-03-01

Full Text Available New soluble biopolyimides were prepared from a diamine derived from an exotic amino acid (4-aminocinnamic acid with several kinds of tetracarboxylic dianhydride. The biopolyimide molecular structural flexibility was tailored by modifying the tetracarboxylic dianhydride moiety. The obtained polyimides were soluble in various solvents such as N-methyl-2-pyrrolidone, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, and even tetrahydrofuran. It was observed that the biopolyimide solubility was greatly dependent upon the structural flexibility (torsion energy. Flexible structure facilitated greater solubility. The synthesized biopolyimides were largely amorphous and had number-average molecular weight (Mn in the range (5–8 × 105. The glass transition temperatures (Tg of the polymers ranged from 259–294 °C. These polymers exhibited good thermal stability without significant weight loss up to 410 °C. The temperatures at 10% weight loss (Td10 for synthesized biopolyimide ranged from 375–397 °C.

Renal excretion of water-soluble contrast media after enema in the neonatal period.

Science.gov (United States)

Kim, Hee Sun; Je, Bo-Kyung; Cha, Sang Hoon; Choi, Byung Min; Lee, Ki Yeol; Lee, Seung Hwa

2014-08-01

When abdominal distention occurs or bowel obstruction is suspected in the neonatal period, a water-soluble contrast enema is helpful for diagnostic and therapeutic purposes. The water-soluble contrast medium is evacuated through the anus as well as excreted via the kidneys in some babies. This study was designed to evaluate the incidence of renal excretion after enemas using water-soluble contrast media and presume the causes. Contrast enemas using diluted water-soluble contrast media were performed in 23 patients under 2 months of age. After the enema, patients were followed with simple abdominal radiographs to assess the improvement in bowel distention, and we could also detect the presence of renal excretion of contrast media on the radiographs. Reviewing the medical records and imaging studies, including enemas and consecutive abdominal radiographs, we evaluated the incidence of renal excretion of water-soluble contrast media and counted the stay duration of contrast media in urinary tract, bladder, and colon. Among 23 patients, 12 patients (52%) experienced the renal excretion of water-soluble contrast media. In these patients, stay-in-bladder durations of contrast media were 1-3 days and stay-in-colon durations of contrast media were 1-10 days, while stay-in-colon durations of contrast media were 1-3 days in the patients not showing renal excretion of contrast media. The Mann-Whitney test for stay-in-colon durations demonstrated the later evacuation of contrast media in the patients with renal excretion of contrast media (p = 0.07). The review of the medical records showed that 19 patients were finally diagnosed as intestinal diseases, including Hirschsprung's disease, meconium ileum, meconium plug syndrome, and small bowel atresia or stenosis. Fisher's exact test between the presence of urinary excretion and intestinal diseases indicated a statistically significant difference (p = 0.04). The intestinal diseases causing bowel obstruction may increase the

Dissolution and Solubility Enhancement of the Highly Lipophilic Drug Phenytoin via Interaction with Poly(N-isopropylacrylamide-co-vinylpyrrolidone) Excipients.

Science.gov (United States)

Widanapathirana, Lakmini; Tale, Swapnil; Reineke, Theresa M

2015-07-06

Excipients of natural or synthetic origin play an important role in pharmaceutical performance to enhance the solubility, bioavailability, release, and stability of insoluble drugs. Herein, a series of seven excipient models was prepared by both homopolymerization and copolymerization of 1-vinyl-2-pyrrolidone (VP) and N-isopropylacrylamide (NIPAAm) by free radical polymerization yielding two homopolymers poly(VP) and poly(NIPAAm) and five copolymers of poly(NIPAAm-co-VP) at difference compositions. While the VP monomer provided aqueous solubility at a variety of conditions to the excipient, the incorporation of NIPAAm into the copolymer offered additional hydrogen bond donating sites to optimize the drug-polymer interactions in the system. Due to the presence of NIPAAm, the copolymers were sensitive to temperature as well. It was found that as the proportion of VP was increased (from 0 to 100%), the lower critical solution temperature (LCST) and the water solubility of the polymer models increased. To examine the role of specific drug-polymer interactions during dissolution on drug solubility and bioavailability, the polymers were formulated with the anticonvulsant drug phenytoin, which is a poorly water-soluble BCS class II drug where oral absorption is limited by the drug solubility. Amorphous solid dispersions (ASD) were prepared via spray drying of phenytoin with the polymer excipient models to contain 10% and 25% by weight drug loading. Physical characterization of the ASDs by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) revealed that the polymers held the drug in a high-energy amorphous phase in all the formulations prepared. All ASDs exhibited improved in vitro dissolution rates compared to drug only and physical mixtures of the polymers and the drug. Drug solubility was the highest with the ASDs containing poly(NIPAAm-co-VP) 60:40 and 50:50, which showed a solubility enhancement of near 14-fold increase compared to pure drug

The solubility-permeability interplay and its implications in formulation design and development for poorly soluble drugs.

Science.gov (United States)

Dahan, Arik; Miller, Jonathan M

2012-06-01

While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

Directory of Open Access Journals (Sweden)

Kyeong-Ok Choi

2016-05-01

Full Text Available The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

Science.gov (United States)

Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

2016-05-20

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

Science.gov (United States)

Dey, Soma; Sreenivasan, K

2014-01-01

Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Significant improvement in the thermal annealing process of optical resonators

Science.gov (United States)

Salzenstein, Patrice; Zarubin, Mikhail

2017-05-01

Thermal annealing performed during process improves the quality of the roughness of optical resonators reducing stresses at the periphery of their surface thus allowing higher Q-factors. After a preliminary realization, the design of the oven and the electronic method were significantly improved thanks to nichrome resistant alloy wires and chopped basalt fibers for thermal isolation during the annealing process. Q-factors can then be improved.

Thermodynamic model of Ni(II) solubility, hydrolysis and complex formation with ISA

Energy Technology Data Exchange (ETDEWEB)

Gonzalez-Siso, Maria Rosa; Duro, Lara; Bruno, Jordi [Amphos21, Barcelona (Spain); Gaona, Xavier; Altmaier, Marcus [Karlsruhe Institute of Technology (KIT), Karlsruhe (Germany). Inst. for Nuclear Waste Disposal

2018-04-01

the low solubility (<10{sup -7} M) of Ni(II) in hyperalkaline pH conditions representative of cementitious environments (10 ≤ pH ≤ 13), which increases to up to 10{sup -5} M in the presence of 0.2 M NaISA. These results significantly improve source term estimations for Ni(II) in environments relevant for the disposal of low and intermediate level radioactive waste (L/ILW). The chemical and thermodynamic models derived in this work can be implemented in geochemical models/calculations, and provide further confidence in the safety analysis of repositories for the disposal of L/ILW.

Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

Energy Technology Data Exchange (ETDEWEB)

Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J

2007-08-29

The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

Solubility of Stevioside and Rebaudioside A in water, ethanol and their binary mixtures

Directory of Open Access Journals (Sweden)

Liliana S. Celaya

2016-10-01

Full Text Available In order to investigate the solubility of Stevioside and Rebaudioside A in different solvents (ethanol, water, ethanol:water 30:70 and ethanol:water 70:30, supersaturated solutions of pre-crystalized steviol glycosides were maintained at different temperatures (from 5 °C to 50 °C to reach equilibrium. Under these conditions significant differences were found in the extent of solubility. Rebaudioside A was poorly soluble in ethanol and water, and Stevioside was poorly soluble in water. Solvent mixtures more effectively promoted solubilisation, and a significant effect of temperature on solubility was observed. The two steviol glycosides showed higher solubilities and this behavior was promoted by the presence of the other sweetener. The polarity indices of the solvents were determined, and helped to explain the observed behavior. Several solute-solvent and solute-solute interactions can occur, along with the incidence of a strong affinity between solvents. The obtained results are in accordance with technological applications of ethanol, water and their binary mixtures for Stevioside and Rebaudioside A separations.

[Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa].

Science.gov (United States)

Jiskra, J; Haluzík, M; Svobodová, J; Haluzíková, D; Nedvídková, J; Parízková, J; Kotrlíková, E

2000-10-25

Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

Science.gov (United States)

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

Application of Liquisolid Technology for Enhancing Solubility and Dissolution of Rosuvastatin

Directory of Open Access Journals (Sweden)

Pavan Ram Kamble

2014-03-01

Full Text Available Purpose: Rosuvastatin is a poorly water soluble drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Hence it is necessary to increase the solubility of the Rosuvastatin. Methods: Several liquisolid tablets formulations containing various drug concentrations in liquid medication (ranging from 15% to 25% w/w were prepared. The ratio of Avicel PH 102 (carrier to Aerosil 200 (coating powder material was kept 10, 20, 30. The prepared liquisolid systems were evaluated for their flow properties and possible drug-excipient interactions by Infrared spectra (IR analysis, differential scanning calorimetry (DSC and X- ray powder diffraction (XRPD. Results: The liquisolid system showed acceptable flow properties. The IR and DSC studies demonstrated that there is no significant interaction between the drug and excipients. The XRPD analysis confirmed formation of a solid solution inside the compact matrix. The tabletting properties of the liquisolid compacts were within the acceptable limits. Liquisolid compacts demonstrated significantly higher drug release rates than those of conventional and marketed tablet due to increasing wetting properties and surface area of the drug. Conclusion: This study shows that liquisolid technique is a promising alternative for improvement of the dissolution rate of water insoluble drug.

The solubilities and solubility products of zirconium hydroxide and oxide after aging at 278, 313, and 333 K

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Taishi; Uemura, Takuya; Sasaki, Takayuki; Takagi, Ikuji [Kyoto Univ. (Japan). Dept. of Nuclear Engineering; Moriyama, Hirotake [Kyoto Univ. (Japan). Research Reactor Inst.

2016-07-01

The solubilities of zirconium hydroxide and oxide after aging at 278, 313, and 333 K were measured at 278, 298, 313, and 333 K in the pH{sub c} range of 0.3-7 in a 0.5 M ionic strength solution of NaClO{sub 4} and HClO{sub 4}. Size distributions of the colloidal species were investigated by ultrafiltration using membranes with different pore sizes, and the solid phases were examined by X-ray diffraction. The apparent solubility of zirconium amorphous hydroxide (Zr(OH){sub 4}(am)), prepared by the oversaturation method, decreased with increasing aging temperature (T{sub a}), and the size distributions obtained after aging at elevated temperatures indicated the growth of the colloidal species. We, therefore, suggested that agglomeration of the colloidal species and dehydration and crystallization of Zr(OH){sub 4}(am) as the solubility-limiting solid phase occurred over the course of aging at elevated temperatures. For sample solutions of the crystalline oxide (ZrO{sub 2}(cr)), the aging temperature had no significant effect on the solubility, but the solubility data at lower temperatures were found to be slightly higher than those at higher temperatures, implying a small fraction of the amorphous components. In the analysis of different solid phases (Zr(OH){sub 4}(s,T{sub a}), T{sub a} = 278, 313, and 333 K) depending on the aging temperatures, the solubility products (K{sub sp}, T{sub a}) were determined at different measurement temperatures, and the enthalpy change (Δ{sub r}H {sup circle}) for Zr{sup 4+} 4OH{sup -} <=> Zr(OH){sub 4}(s,T{sub a}) was calculated using the van't Hoff equation. The solid-phase-transformation process at elevated temperatures was also analyzed based on the obtained K{sub sp}, T{sub a} and Δ{sub r}H {sup circle} values.

Indomethacin solubility estimation in 1,4-dioxane + water mixtures by the extended hildebrand solubility approach

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Miller A Ruidiaz

2011-09-01

Full Text Available Extended Hildebrand Solubility Approach (EHSA was successfully applied to evaluate the solubility of Indomethacin in 1,4-dioxane + water mixtures at 298.15 K. An acceptable correlation-performance of EHSA was found by using a regular polynomial model in order four of the W interaction parameter vs. solubility parameter of the mixtures (overall deviation was 8.9%. Although the mean deviation obtained was similar to that obtained directly by means of an empiric regression of the experimental solubility vs. mixtures solubility parameters, the advantages of EHSA are evident because it requires physicochemical properties easily available for drugs.

Experimental studies to validate model calculations and maximum solubility limits for Plutonium and Americium

International Nuclear Information System (INIS)

2017-01-01

This report focuses on studies of KIT-INE to derive a significantly improved description of the chemical behaviour of Americium and Plutonium in saline NaCl, MgCl 2 and CaCl 2 brine systems. The studies are based on new experimental data and aim at deriving reliable Am and Pu solubility limits for the investigated systems as well as deriving comprehensive thermodynamic model descriptions. Both aspects are of high relevance in the context of potential source term estimations for Americium and Plutonium in aqueous brine systems and related scenarios. Americium and Plutonium are long-lived alpha emitting radionuclides which due to their high radiotoxicity need to be accounted for in a reliable and traceable way. The hydrolysis of trivalent actinides and the effect of highly alkaline pH conditions on the solubility of trivalent actinides in calcium chloride rich brine solutions were investigated and a thermodynamic model derived. The solubility of Plutonium in saline brine systems was studied under reducing and non-reducing conditions and is described within a new thermodynamic model. The influence of dissolved carbonate on Americium and Plutonium solubility in MgCl 2 solutions was investigated and quantitative information on Am and Pu solubility limits in these systems derived. Thermodynamic constants and model parameter derived in this work are implemented in the Thermodynamic Reference Database THEREDA owned by BfS. According to the quality assurance approach in THEREDA, is was necessary to publish parts of this work in peer-reviewed scientific journals. The publications are focused on solubility experiments, spectroscopy of aquatic and solid species and thermodynamic data. (Neck et al., Pure Appl. Chem., Vol. 81, (2009), pp. 1555-1568., Altmaier et al., Radiochimica Acta, 97, (2009), pp. 187-192., Altmaier et al., Actinide Research Quarterly, No 2., (2011), pp. 29-32.).

Bioinspired co-crystals of Imatinib providing enhanced kinetic solubility.

Science.gov (United States)

Reggane, Maude; Wiest, Johannes; Saedtler, Marco; Harlacher, Cornelius; Gutmann, Marcus; Zottnick, Sven H; Piechon, Philippe; Dix, Ina; Müller-Buschbaum, Klaus; Holzgrabe, Ulrike; Meinel, Lorenz; Galli, Bruno

2018-05-04

Realizing the full potential of co-crystals enhanced kinetic solubility demands a comprehensive understanding of the mechanisms of dissolution, phase conversion, nucleation and crystal growth, and of the complex interplay between the active pharmaceutical ingredient (API), the coformer and co-existing forms in aqueous media. One blueprint provided by nature to keep poorly water-soluble bases in solution is the complexation with phenolic acids. Consequently, we followed a bioinspired strategy for the engineering of co-crystals of a poorly water-soluble molecule - Imatinib - with a phenolic acid, syringic acid (SYA). The dynamics of dissolution and solution-mediated phase transformations were monitored by Nuclear Magnetic Resonance (NMR) spectroscopy, providing mechanistic insights into the 60 fold-increased long lasting concentrations achieved by the syringate co-crystals as compared to Imatinib base and Imatinib mesylate. This lasting effect was linked to SYA's ability to delay the formation and nucleation of Imatinib hydrate - the thermodynamically stable form in aqueous media - through a metastable association of SYA with Imatinib in solution. Results from permeability studies evidenced that SYA did not impact Imatinib's permeability across membranes while suggesting improved bioavailability through higher kinetic solubility at the biological barriers. These results reflect that some degree of hydrophobicity of the coformer might be key to extend the kinetic solubility of co-crystals with hydrophobic APIs. Understanding how kinetic supersaturation can be shaped by the selection of an interactive coformer may help achieving the needed performance of new forms of poorly water-soluble, slowly dissolving APIs. Copyright © 2018. Published by Elsevier B.V.

Solubility Temperature Dependence Predicted from 2D Structure

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Alex Avdeef

2015-12-01

Full Text Available The objective of the study was to find a computational procedure to normalize solubility data determined at various temperatures (e.g., 10 – 50 oC to values at a “reference” temperature (e.g., 25 °C. A simple procedure was devised to predict enthalpies of solution, ΔHsol, from which the temperature dependence of intrinsic (uncharged form solubility, log S0, could be calculated. As dependent variables, values of ΔHsol at 25 °C were subjected to multiple linear regression (MLR analysis, using melting points (mp and Abraham solvation descriptors. Also, the enthalpy data were subjected to random forest regression (RFR and recursive partition tree (RPT analyses. A total of 626 molecules were examined, drawing on 2040 published solubility values measured at various temperatures, along with 77 direct calori    metric measurements. The three different prediction methods (RFR, RPT, MLR all indicated that the estimated standard deviations in the enthalpy data are 11-15 kJ mol-1, which is concordant with the 10 kJ mol-1 propagation error estimated from solubility measurements (assuming 0.05 log S errors, and consistent with the 7 kJ mol-1 average reproducibility in enthalpy values from interlaboratory replicates. According to the MLR model, higher values of mp, H‑bond acidity, polarizability/dipolarity, and dispersion forces relate to more positive (endothermic enthalpy values. However, molecules that are large and have high H-bond basicity are likely to possess negative (exothermic enthalpies of solution. With log S0 values normalized to 25 oC, it was shown that the interlaboratory average standard deviations in solubility measurement are reduced to 0.06 ‑ 0.17 log unit, with higher errors for the least-soluble druglike molecules. Such improvements in data mining are expected to contribute to more reliable in silico prediction models of solubility for use in drug discovery.

Enhancement of solubility and dissolution rate of atorvastatin ...

African Journals Online (AJOL)

Purpose: To investigate the formation of atorvastatin calcium (AC) co-crystal to improve its solubility and dissolution rate. Method: Co-crystallization of AC in equimolar ratio with isonicotinamide (INA) was carried out by slow solvent evaporation method using methanol. The solid obtained was characterized by powder x-ray ...

Solubility and Permeability Studies of Aceclofenac in Different Oils

African Journals Online (AJOL)

assess the in vivo bioavailability of the drug [1]. Forty percent of ... administration with hepatic first-pass metabolism. [11]. Due its ... suitable oils that would improve solubility and in .... Baboota S, Faisal MS, Ali J, Ahuja A. Effect of poloxamer.

Soluble Non-ammonia Nitrogen in Ruminal and Omasal Digesta of Korean Native Steers Supplemented with Soluble Proteins

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C. W. Choi

2012-09-01

Full Text Available An experiment was conducted to study the effect of soluble protein supplements on concentration of soluble non-ammonia nitrogen (SNAN in the liquid phase of ruminal (RD and omasal digesta (OD of Korean native steers, and to investigate diurnal pattern in SNAN concentration in RD and OD. Three ruminally cannulated Korean native steers in a 3×3 Latin square design consumed a basal diet of rice straw and corn-based concentrate (control, and that supplemented (kg/d DM basis with intact casein (0.24; IC or acid hydrolyzed casein (0.46; AHC. Ruminal digesta was sampled using a vacuum pump, whereas OD was collected using an omasal sampling system at 2.0 h intervals after a morning feeding. The SNAN fractions (free amino acid (AA, peptide and soluble protein in RD and OD were assessed using the ninhydrin assay. Concentrations of free AA and total SNAN in RD were significantly (p<0.05 lower than those in OD. Although free AA concentration was relatively high, mean peptide was quantitatively the most important fraction of total SNAN in both RD and OD, indicating that degradation of peptide to AA rather than hydrolysis of soluble protein to peptide or deamination may be the most limiting step in rumen proteolysis of Korean native steers. Diurnal variation in peptide concentration in OD for the soluble protein supplemented diets during the feeding cycle peaked 2 h post-feeding and decreased thereafter whereas that for the control was relatively constant during the entire feeding cycle. Diurnal variation in peptide concentration was rather similar between RD and OD.

Significant Improvement of Catalytic Efficiencies in Ionic Liquids

International Nuclear Information System (INIS)

Song, Choong Eui; Yoon, Mi Young; Choi, Doo Seong

2005-01-01

The use of ionic liquids as reaction media can confer many advantages upon catalytic reactions over reactions in organic solvents. In ionic liquids, catalysts having polar or ionic character can easily be immobilized without additional structural modification and thus the ionic solutions containing the catalyst can easily be separated from the reagents and reaction products, and then, be reused. More interestingly, switching from an organic solvent to an ionic liquid often results in a significant improvement in catalytic performance (e.g., rate acceleration, (enantio)selectivity improvement and an increase in catalyst stability). In this review, some recent interesting results which can nicely demonstrate these positive 'ionic liquid effect' on catalysis are discussed

On the solubility of yttrium in RuO2

International Nuclear Information System (INIS)

Music, Denis; Zumdick, Naemi A.; Hallstedt, Bengt; Schneider, Jochen M.

2011-01-01

We have investigated the solubility of Y in rutile RuO 2 using experimental and theoretical methods. Nanostructured Ru-Y-O thin films were synthesized via combinatorial reactive sputtering with an O/metal ratio of 2.6 and a Y content of 0.3 to 12.6 at. %. A solubility limit of 1.7 at. % was identified using x-ray photoelectron spectroscopy and x-ray diffraction. Based on ab initio and thermodynamic modeling, the solubility of Y can be understood. Smaller Y amounts are incorporated into the lattice, forming a metastable film, with local structural deformations due to size effects. As the Y content is increased, extensive local structural deformations are observed, but phase separation does not occur due to kinetic limitations. Nanostructured RuO 2 alloyed with Y might lead to enhanced phonon scattering and quantum confinement effects, which in turn improve the thermoelectric efficiency.

The solubility of hydrogen and deuterium in alloyed, unalloyed and impure plutonium metal

Energy Technology Data Exchange (ETDEWEB)

Richmond, Scott [Los Alamos National Laboratory; Bridgewater, Jon S [Los Alamos National Laboratory; Ward, John W [Los Alamos National Laboratory; Allen, Thomas A [Los Alamos National Laboratory

2009-01-01

Pressure-Composition-Temperature (PCT) data are presented for the plutonium-hydrogen (Pu-H) and plutonium-deuterium (Pu-D) systems in the solubility region up to terminal solubility (precipitation of PuH{sub 2}). The heats of solution for PuH{sub s} and PuD{sub s} are determined from PCT data in the ranges 350-625 C for gallium alloyed Pu and 400-575 C for unalloyed Pu. The solubility of high purity plutonium alloyed with 2 at.% gallium is compared to high purity unalloyed plutonium. Significant differences are found in hydrogen solubility for unalloyed Pu versus gallium alloyed Pu. Differences in hydrogen solubility due to an apparent phase change are observable in the alloyed and unalloyed solubilities. The effect of iron impurities on Pu-Ga alloyed Pu is shown via hydrogen solubility data as preventing complete homogenization.

The solubility of hydrogen and deuterium in alloyed, unalloyed and impure plutonium metal

International Nuclear Information System (INIS)

Richmond, S; Bridgewater, J S; Ward, J W; Allen, T H

2010-01-01

Pressure-Composition-Temperature (PCT) data are presented for the plutonium-hydrogen (Pu-H) and plutonium-deuterium (Pu-D) systems in the solubility region up to terminal solubility (precipitation of PuH 2 ). The heats of solution for PuH S and PuD S are determined from PCT data in the ranges 350-625 deg. C for gallium alloyed Pu and 400-575 deg. C for unalloyed Pu. The solubility of high purity plutonium alloyed with 2 at.% gallium is compared to high purity unalloyed plutonium. Significant differences are found in hydrogen solubility for unalloyed Pu versus gallium alloyed Pu. Differences in hydrogen solubility due to an apparent phase change are observable in the alloyed and unalloyed solubilities. The effect of iron impurities on Pu-Ga alloyed Pu is shown via hydrogen solubility data as preventing complete homogenization.

Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

DEFF Research Database (Denmark)

Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

2007-01-01

Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). In PCOS, positive correlations were found between central fat mass and sCD36 (r=0.43), hs......CRP (r=0.43), and IL-6 (r=0.42), all pPCOS patients and controls (n=44). sCD36 and oxLDL were significant...

40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

Science.gov (United States)

2010-07-01

... in water is a significant parameter because: (A) The spatial and temporal movement (mobility) of a... Solubility in Water of Slightly Soluble, Low Volatility Organic Substances ER15DE00.054 1 = Leveling vessel...

Measurement of solubility of hydrogen isotopes in Li-Pb by adsorption and desorption method

International Nuclear Information System (INIS)

Edao, Yuki; Katayama, K.; Fukada, S.

2014-01-01

Measurement of tritium solubility in lithium lead eutectic alloy (Li-Pb) has been performed under the Japan-US collaboration work of 'TITAN'. The present paper reports that results of H and D solubility in Li-Pb which melted in an alumina tube determined by means of a constant volume method, and also reports an experimental apparatus for measurement of tritium solubility in Li-Pb in a tungsten crucible is improved and examined in the STAR facility of the Idaho National Laboratory. It was shown that H solubility in Li-Pb was easily influenced by impurities, interaction with surrounding materials and evaporated Li-Pb. The influences were suggested to be caused by large scattering among the previously reported data on solubility of hydrogen isotopes in Li-Pb. (author)

Training directionally selective motion pathways can significantly improve reading efficiency

Science.gov (United States)

Lawton, Teri

2004-06-01

This study examined whether perceptual learning at early levels of visual processing would facilitate learning at higher levels of processing. This was examined by determining whether training the motion pathways by practicing leftright movement discrimination, as found previously, would improve the reading skills of inefficient readers significantly more than another computer game, a word discrimination game, or the reading program offered by the school. This controlled validation study found that practicing left-right movement discrimination 5-10 minutes twice a week (rapidly) for 15 weeks doubled reading fluency, and significantly improved all reading skills by more than one grade level, whereas inefficient readers in the control groups barely improved on these reading skills. In contrast to previous studies of perceptual learning, these experiments show that perceptual learning of direction discrimination significantly improved reading skills determined at higher levels of cognitive processing, thereby being generalized to a new task. The deficits in reading performance and attentional focus experienced by the person who struggles when reading are suggested to result from an information overload, resulting from timing deficits in the direction-selectivity network proposed by Russell De Valois et al. (2000), that following practice on direction discrimination goes away. This study found that practicing direction discrimination rapidly transitions the inefficient 7-year-old reader to an efficient reader.

Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

Science.gov (United States)

Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

2016-09-10

The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Solubility of β-carotene in ethanol- and triolein-modified CO2

International Nuclear Information System (INIS)

Araus, Karina A.; Canales, Roberto I.; Valle, Jose M. del; Fuente, Juan C. de la

2011-01-01

Highlights: → We measure solubility of β-carotene in pure CO 2 , and with ethanol and triolein as co-solvents. → We model the solubility of β-carotene in pure CO 2 , and with co-solvents. → The co-solvent effect of triolein over solubility of β-carotene in CO 2 was higher than ethanol. - Abstract: Modification of an experimental device and methodology improved speed and reproducibility of measurement of solubility of β-carotene in pure and modified SuperCritical (SC) CO 2 at (313 to 333) K. Solubilities of β-carotene in pure CO 2 at (17 to 34) MPa ranged (0.17 to 1.06) μmol/mol and agreed with values reported in literature. The solubility of β-carotene in CO 2 modified with (1.2 to 1.6) % mol ethanol increased by a factor of 1.7 to 3.0 as compared to its solubility in pure CO 2 under equivalent conditions. The concentration of triolein in equilibrated ternary (CO 2 + β-carotene + triolein) mixtures having excess triolein reached values (0.01 to 0.39) mmol/mol corresponding to its solubility in pure SC CO 2 under equivalent conditions. Under these conditions, the solubility of β-carotene in triolein-modified CO 2 increased by a factor of up to 4.0 in relation with its solubility in pure CO 2 at comparable system temperature and pressure, reaching an uppermost value of 3.3 μmol/mol at 333 K and 32 MPa. Unlike in the case of ethanol, where enhancements in solubility where relatively independent on system conditions, solubility enhancements using triolein as co-solvent increased markedly with system pressure, being larger than using (1.2 to 1.6) % mol ethanol at about (24 to 28) MPa, depending on system temperature. The increase in the solubility β-carotene in SC CO 2 as a result of using ethanol or triolein as co-solvent apparently does not depend on the increase in density associated with the dissolution of the co-solvent in CO 2 . Enhancements may be due to an increase in the polarizability of SC CO 2 , which possibly growths markedly as triolein

Effects of a low severity prescribed fire on water-soluble elements in ash from a cork oak (Quercus suber) forest located in the northeast of the Iberian Peninsula

Science.gov (United States)

Pereira, P.; beda, X.; Martin, D.; Mataix-Solera, J.; Guerrero, C.

2011-01-01

Wildfire is the major disturbance in Mediterranean forests. Prescribed fire can be an alternative to reduce the amount of fuel and hence decrease the wildfire risk. However the effects of prescribed fire must be studied, especially on ash properties, because ash is an important nutrient source for ecosystem recovery. The aim of this study is to determine the effects of a low severity prescribed fire on water-soluble elements in ash including pH, electrical conductivity (EC), calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), aluminum (Al), manganese (Mn), iron (Fe), zinc (Zn), silica (SiO2) and total sulphur (TS). A prescribed fire was conducted in a cork oak (Quercus suber) (Q.S) forest located in the northeast part of the Iberian Peninsula. Samples were collected from a flat plot of 40??70m mainly composed of Q.S and Quercus robur (Q.R) trees. In order to understand the effects of the prescribed fire on the soluble elements in ash, we conducted our data analysis on three data groups: all samples, only Q.S samples and only Q.R samples. All three sample groups exhibited a significant increase in pH, EC (p<0.001), water-soluble Ca, Mg, Na, SiO2 and TS and a decrease in water-soluble Mn, Fe and Zn. Differences were identified between oak species for water-soluble K, Al and Fe. In Q.S samples we registered a significant increase in the first two elements p<0.001 and p<0.01, respectively, and a non-significant impact in the third, at p<0.05. In Q.R data we identified a non-significant impact on water-soluble K and Al and a significant decrease in water-soluble Fe (p<0.05). These differences are probably due to vegetation characteristics and burn severity. The fire induced a higher variability in the ash soluble elements, especially in Q.S samples, that at some points burned with higher severity. The increase of pH, EC, Ca, Mg, Na and K will improve soil fertility, mainly in the study area where soils are acidic. The application of this low severity prescribed

Determination of water-soluble and fat-soluble vitamins in tears and blood serum of infants and parents by liquid chromatography/mass spectrometry.

Science.gov (United States)

Khaksari, Maryam; Mazzoleni, Lynn R; Ruan, Chunhai; Kennedy, Robert T; Minerick, Adrienne R

2017-02-01

Tears serve as a viable diagnostic fluid with advantages including less invasive sample to collect and less complex to prepare for analysis. Several water-soluble and fat-soluble vitamins were detected and quantified in human tears and compared with blood serum levels. Samples from 15 family pairs, each pair consisting of a four-month-old infant and one parent were analyzed; vitamin concentrations were compared between tears and blood serum for individual subjects, between infants and parents, and against self-reported dietary intakes. Water-soluble vitamins B 1 , B 2 , B 3 (nicotinamide), B 5 , B 9 and fat-soluble vitamin E (α-tocopherol) were routinely detected in tears and blood serum while fat-soluble vitamin A (retinol) was detected only in blood serum. Water-soluble vitamin concentrations measured in tears and blood serum of single subjects were comparable, while higher concentrations were measured in infants compared to their parents. Fat-soluble vitamin E concentrations were lower in tears than blood serum with no significant difference between infants and parents. Serum vitamin A concentrations were higher in parents than infants. Population trends were compiled and quantified using a cross correlation factor. Strong positive correlations were found between tear and blood serum concentrations of vitamin E from infants and parents and vitamin B 3 concentrations from parents, while slight positive correlations were detected for infants B 3 and parents B 1 and B 2 concentrations. Correlations between infants and parents were found for the concentrations of B 1 , B 2 , B 3 , and E in tears, and the concentrations of B 2, A, and E in blood serum. Stronger vitamin concentration correlations were found between infants and parents for the breast-fed infants, while no significant difference was observed between breast-fed and bottle-fed infants. This work is the first to demonstrate simultaneous vitamin A, B, and E detection and to quantify correlations between

An Improved Variant of Soybean Type 1 Diacylglycerol Acyltransferase Increases the Oil Content and Decreases the Soluble Carbohydrate Content of Soybeans.

Science.gov (United States)

Roesler, Keith; Shen, Bo; Bermudez, Ericka; Li, Changjiang; Hunt, Joanne; Damude, Howard G; Ripp, Kevin G; Everard, John D; Booth, John R; Castaneda, Leandro; Feng, Lizhi; Meyer, Knut

2016-06-01

Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans. © 2016 American Society of Plant Biologists. All Rights Reserved.

Soluble polymer conjugates for drug delivery.

Science.gov (United States)

Minko, Tamara

2005-01-01

The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

Argon solubility in liquid steel

NARCIS (Netherlands)

Boom, R; Dankert, O; Van Veen, A; Kamperman, AA

2000-01-01

Experiments have been performed to establish the solubility of argon in liquid interstitial-free steel. The solubility appears to be lower than 0.1 at ppb, The results are in line with argon solubilities reported in the literature on liquid iron. Semiempirical theories and calculations based on the

[Variation of polysaccharides and alcohol-soluble extracts content of Dendrobium officinale].

Science.gov (United States)

Yu, Qiao-xian; Guo, Ying-ying; Si, Jin-ping; Wu, Ling-shang; Wang, Lin-hua

2014-12-01

To reveal the variation of polysaccharides and alcohol-soluble extract contents of Dendrobium officinale, the polysaccharides and alcohol-soluble extracts contents of three D. officinale strains were determined by phenol-sulfuric acid method and hot-dip method, respectively. The results showed that the contents of polysaccharides and alcohol-soluble extracts and their total content were significantly different among D. officinale samples collected in different periods, and the variations were closely related to the phenology of D. officinale. Additionally, the quality variation of polysaccharides was closely related to the flowering of D. officinale, while the alcohol-soluble extracts was closely associated to the formation and germination of buds. According to the dynamic variation of these two compounds, it is more reasonable to harvest D. officinale at biennials pre-bloom than at specific harvesting month considering polysaccharides content. It is better to harvest before the germination of buds considering alcohol-soluble extracts. While with regards to both polysaccharides and alcohol-soluble extract, it is better to harvest this plant at the period from the sprouting to pre-bloom next year.

Water Solubility of Plutonium and Uranium Compounds and Residues at TA-55

International Nuclear Information System (INIS)

Reilly, Sean Douglas; Smith, Paul Herrick; Jarvinen, Gordon D.; Prochnow, David Adrian; Schulte, Louis D.; DeBurgomaster, Paul Christopher; Fife, Keith William; Rubin, Jim; Worl, Laura Ann

2016-01-01

Understanding the water solubility of plutonium and uranium compounds and residues at TA-55 is necessary to provide a technical basis for appropriate criticality safety, safety basis and accountability controls. Individual compound solubility was determined using published solubility data and solution thermodynamic modeling. Residue solubility was estimated using a combination of published technical reports and process knowledge of constituent compounds. The scope of materials considered includes all compounds and residues at TA-55 as of March 2016 that contain Pu-239 or U-235 where any single item in the facility has more than 500 g of nuclear material. This analysis indicates that the following materials are not appreciably soluble in water: plutonium dioxide (IDC=C21), plutonium phosphate (IDC=C66), plutonium tetrafluoride (IDC=C80), plutonium filter residue (IDC=R26), plutonium hydroxide precipitate (IDC=R41), plutonium DOR salt (IDC=R42), plutonium incinerator ash (IDC=R47), uranium carbide (IDC=C13), uranium dioxide (IDC=C21), U 3 O 8 (IDC=C88), and uranium filter residue (IDC=R26). This analysis also indicates that the following materials are soluble in water: plutonium chloride (IDC=C19) and uranium nitrate (IDC=C52). Equilibrium calculations suggest that PuOCl is water soluble under certain conditions, but some plutonium processing reports indicate that it is insoluble when present in electrorefining residues (R65). Plutonium molten salt extraction residues (IDC=R83) contain significant quantities of PuCl 3 , and are expected to be soluble in water. The solubility of the following plutonium residues is indeterminate due to conflicting reports, insufficient process knowledge or process-dependent composition: calcium salt (IDC=R09), electrorefining salt (IDC=R65), salt (IDC=R71), silica (IDC=R73) and sweepings/screenings (IDC=R78). Solution thermodynamic modeling also indicates that fire suppression water buffered with a commercially-available phosphate

Water Solubility of Plutonium and Uranium Compounds and Residues at TA-55

Energy Technology Data Exchange (ETDEWEB)

Reilly, Sean Douglas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Smith, Paul Herrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Jarvinen, Gordon D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Prochnow, David Adrian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Schulte, Louis D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; DeBurgomaster, Paul Christopher [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Fife, Keith William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Rubin, Jim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States; Worl, Laura Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States

2016-06-13

Understanding the water solubility of plutonium and uranium compounds and residues at TA-55 is necessary to provide a technical basis for appropriate criticality safety, safety basis and accountability controls. Individual compound solubility was determined using published solubility data and solution thermodynamic modeling. Residue solubility was estimated using a combination of published technical reports and process knowledge of constituent compounds. The scope of materials considered includes all compounds and residues at TA-55 as of March 2016 that contain Pu-239 or U-235 where any single item in the facility has more than 500 g of nuclear material. This analysis indicates that the following materials are not appreciably soluble in water: plutonium dioxide (IDC=C21), plutonium phosphate (IDC=C66), plutonium tetrafluoride (IDC=C80), plutonium filter residue (IDC=R26), plutonium hydroxide precipitate (IDC=R41), plutonium DOR salt (IDC=R42), plutonium incinerator ash (IDC=R47), uranium carbide (IDC=C13), uranium dioxide (IDC=C21), U₃O₈ (IDC=C88), and uranium filter residue (IDC=R26). This analysis also indicates that the following materials are soluble in water: plutonium chloride (IDC=C19) and uranium nitrate (IDC=C52). Equilibrium calculations suggest that PuOCl is water soluble under certain conditions, but some plutonium processing reports indicate that it is insoluble when present in electrorefining residues (R65). Plutonium molten salt extraction residues (IDC=R83) contain significant quantities of PuCl₃, and are expected to be soluble in water. The solubility of the following plutonium residues is indeterminate due to conflicting reports, insufficient process knowledge or process-dependent composition: calcium salt (IDC=R09), electrorefining salt (IDC=R65), salt (IDC=R71), silica (IDC=R73) and sweepings/screenings (IDC=R78). Solution thermodynamic modeling also indicates that fire suppression water buffered with a

Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran.

Science.gov (United States)

Parhizkar, Elahehnaz; Ahmadi, Fatemeh; Daneshamouz, Saeid; Mohammadi-Samani, Soliman; Sakhteman, Amirhossein; Parhizkar, Golnaz

2017-11-24

Cabazitaxel (CTX) is a second- generation taxane derivative, a class of potent anticancer drugs with very low water solubility. CTX is used in patients with resistant prostate cancer unresponsive to the first generation taxane, docetaxel. Currently marketed formulations of CTX contain high concentrations of surfactant and ethanol, which cause severe hypersensitivity reactions in patients. In order to increase its solubility, two hemiester analogs; CTX-succinate and CTX-glutarate were synthesized and characterized. To improve the solubility of hemiesters even more, dextran as a biocompatible polymer was also conjugated to hemiester analogs. MTT assay was performed on MCF-7 cell line to evaluate the cytotoxicity effect of hemiesters and conjugates. Based on the results, hemiester analogs increased water solubility of the drug up to about 3 and 8 fold. Conjugation to dextran enhanced the CTX solubility to more than 1500 fold. These conjugates released the conjugated CTX in less than 24 hours in a pH dependent manner and showed proper hemocompatibility characteristics. The hemiesters had approximately similar cytotoxicity in comparison with CTX and the dextran conjugates showed higher cytotoxicity effect on MCF-7 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhancement of soluble CD28 levels in the serum of Graves' disease.

Science.gov (United States)

Sun, Zhongwen; Yi, Lixian; Tao, Hong; Huang, Jingfang; Jin, Zhenghong; Xiao, Yang; Feng, Caiyun; Sun, Jing

2014-01-01

Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.

Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin

DEFF Research Database (Denmark)

Søndergaard, Klaus; Deleuran, Mette; Heickendorff, Lene

1998-01-01

In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma...... from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from...

Solubilization of poorly water-soluble drugs using solid dispersions.

Science.gov (United States)

Tran, Thao T-D; Tran, Phuong H-L; Khanh, Tran N; Van, Toi V; Lee, Beom-Jin

2013-08-01

Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible.

Equilibrium solubility versus intrinsic dissolution: characterization of lamivudine, stavudine and zidovudine for BCS classification

Directory of Open Access Journals (Sweden)

André Bersani Dezani

2013-12-01

Full Text Available Solubility and dissolution rate of drugs are of major importance in pre-formulation studies of pharmaceutical dosage forms. The solubility improvement allows the drugs to be potential biowaiver candidates and may be a good way to develop more dose-efficient formulations. Solubility behaviour of lamivudine, stavudine and zidovudine in individual solvents (under pH range of 1.2 to 7.5 was studied by equilibrium solubility and intrinsic dissolution methods. In solubility study by equilibrium method (shake-flask technique, known amounts of drug were added in each media until to reach saturation and the mixture was subjected to agitation of 150 rpm for 72 hours at 37 ºC. In intrinsic dissolution test, known amount of each drug was compressed in the matrix of Wood's apparatus and subjected to dissolution in each media with agitation of 50 rpm at 37 ºC. In solubility by equilibrium method, lamivudine and zidovudine can be considered as highly soluble drugs. Although stavudine present high solubility in pH 4.5, 6.8, 7.5 and water, the solubility determination in pH 1.2 was not possible due stability problems. Regarding to intrinsic dissolution, lamivudine and stavudine present high speed of dissolution. Considering a boundary value presented by Yu and colleagues (2004, all drugs studied present high solubility characteristics in intrinsic dissolution method. Based on the obtained results, intrinsic dissolution seems to be superior for solubility studies as an alternative method for biopharmaceutical classification purposes.

PES/POSS Soluble Veils as Advanced Modifiers for Multifunctional Fiber Reinforced Composites

Directory of Open Access Journals (Sweden)

Gianluca Cicala

2017-07-01

Full Text Available Novel polyhedral oligomeric silsesquioxanes (POSS-filled thermoplastic electrospun veils were used to tailor the properties of the interlaminar region of epoxy-based composites. The veils were designed to be soluble upon curing in the epoxy matrix, so that POSS could be released within the interlaminar region. Three different POSS contents, varying from 1 to 10 wt %, were tested while the percentage of coPolyethersulphone (coPES dissolved in the epoxy resin was kept to a fixed value of 10 wt %. Good quality veils could be obtained at up to 10 wt % of POSS addition, with the nanofibers’ diameters varying from 861 nm for the coPES to 428 nm upon POSS addition. The feasibility of the soluble veils to disperse POSS in the interlaminar region was proved, and the effect of POSS on phase morphology and viscoelastic properties studied. POSS was demonstrated to significantly affect the morphology and viscoelastic properties of epoxy composites, especially for the percentages 1% and 5%, which enabled the composites to avoid POSS segregates occurring. A dynamic mechanical analysis showed a significant improvement to the storage modulus, and a shift of more than 30 °C due to the POSS cages hindering the motion of the molecular chains and network junctions.

Effect of Fermentation and Cooking on Soluble and Bound Phenolic Profiles of Finger Millet Sour Porridge.

Science.gov (United States)

Gabaza, Molly; Shumoy, Habtu; Muchuweti, Maud; Vandamme, Peter; Raes, Katleen

2016-10-12

The aim of this study was to evaluate the soluble and bound phenolic content of finger millet and the impact of process induced changes on phenolic profiles of their sour porridge. Finger millet porridge and intermediate products were collected from four groups of households in the Hwedza communal area, Zimbabwe, after which soluble and bound phenolic compounds (PC) including condensed tannins (CT) were quantified. Bound PC and CT contributed 95% of the total PC and CT. The CT were only detected in the red varieties. Major individual PC identified were catechin occurring in the soluble fraction only, while ferulic, sinapic, and salicylic acid were mainly present in the bound fraction. Fermentation and cooking caused a more than 2-fold increase in soluble PC, CT, and individual PC. Improved traditional processing techniques optimized for improved bioavailability and health benefits of phenolics are highly relevant for the low income populations.

Low hygroscopic spray-dried powders with trans-glycosylated food additives enhance the solubility and oral bioavailability of ipriflavone.

Science.gov (United States)

Fujimori, Miki; Kadota, Kazunori; Kato, Kouki; Seto, Yoshiki; Onoue, Satomi; Sato, Hideyuki; Ueda, Hiroshi; Tozuka, Yuichi

2016-01-01

The improvement in the solubility and dissolution rate may promote a superior absorption property towards the human body. The spray-dried powders (SDPs) of ipriflavone, which was used as a model hydrophobic flavone, with trans-glycosylated rutin (Rutin-G) showed the highest solubilizing effect of ipriflavone among three types of trans-glycosylated food additives. The SDPs of ipriflavone with Rutin-G have both a significant higher dissolution rate and solubility enhancement of ipriflavone. This spray-dried formulation of ipriflavone with Rutin-G exhibited a low hygroscopicity as a critical factor in product preservation. In addition, an improvement in the oral absorption of ipriflavone was achieved by means of preparing composite particles of ipriflavone/Rutin-G via spray drying, indicating a 4.3-fold increase in the area under the plasma concentration-time curve compared with that of untreated ipriflavone. These phenomena could be applicable to food ingredients involving hydrophobic flavones for producing healthy food with a high quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Students’ misconceptions on solubility equilibrium

Science.gov (United States)

Setiowati, H.; Utomo, S. B.; Ashadi

2018-05-01

This study investigated the students’ misconceptions of the solubility equilibrium. The participants of the study consisted of 164 students who were in the science class of second year high school. Instrument used is two-tier diagnostic test consisting of 15 items. Responses were marked and coded into four categories: understanding, misconception, understand little without misconception, and not understanding. Semi-structured interviews were carried out with 45 students according to their written responses which reflected different perspectives, to obtain a more elaborated source of data. Data collected from multiple methods were analyzed qualitatively and quantitatively. Based on the data analysis showed that the students misconceptions in all areas in solubility equilibrium. They had more misconceptions such as in the relation of solubility and solubility product, common-ion effect and pH in solubility, and precipitation concept.

Radiation crosslinking of starch/water-soluble polymer blends for hydrogel

International Nuclear Information System (INIS)

Hashim, K.; Mohid, N.; Bahari, K.; Dahlan, K.Z.

2000-01-01

Water-soluble polymers such as PVP(polyvinyl pyrrolidone) and PVA(polyvinyl alcohol), in aqueous solution can form hydrogel easily upon gamma or electron beam irradiation. The properties of hydrogels, particularly for wound dressing application, can be further improved by adding sago starch to the blend. Results show improved gel strength and elongation properties of the hydrogel with increasing sago concentration. It was found that the PVA/sago hydrogel gives better gel strength and elongation than the PVP/sago hydrogel. The tackiness property of the PVA/sago hydrogel increased with increase amount of sago starch added. In case of PVP/sago hydrogel, the tackiness property shows significant increase with increasing amount of sago except for the 5%PVP composition. The swelling properties of PVP/sago and PVA/sago hydrogel decreased with increasing amount of sago but the crosslink density of the hydrogels also reduced. (author)

Radiation crosslinking of starch/water-soluble polymer blends for hydrogel

Energy Technology Data Exchange (ETDEWEB)

Hashim, K.; Mohid, N.; Bahari, K.; Dahlan, K.Z. [Radiation Processing Technology Division, Malaysian Institute Nuclear Technology Research Malaysia (MINT), Bangi, 43000 Kajang (Malaysia)

2000-03-01

Water-soluble polymers such as PVP(polyvinyl pyrrolidone) and PVA(polyvinyl alcohol), in aqueous solution can form hydrogel easily upon gamma or electron beam irradiation. The properties of hydrogels, particularly for wound dressing application, can be further improved by adding sago starch to the blend. Results show improved gel strength and elongation properties of the hydrogel with increasing sago concentration. It was found that the PVA/sago hydrogel gives better gel strength and elongation than the PVP/sago hydrogel. The tackiness property of the PVA/sago hydrogel increased with increase amount of sago starch added. In case of PVP/sago hydrogel, the tackiness property shows significant increase with increasing amount of sago except for the 5%PVP composition. The swelling properties of PVP/sago and PVA/sago hydrogel decreased with increasing amount of sago but the crosslink density of the hydrogels also reduced. (author)

[Emission Characteristics of Water-Soluble Ions in Fumes of Coal Fired Boilers in Beijing].

Science.gov (United States)

Hu, Yue-qi; Ma, Zhao-hui; Feng, Ya-jun; Wang, Chen; Chen, Yuan-yuan; He, Ming

2015-06-01

Selecting coal fired boilers with typical flue gas desulfurization and dust extraction systems in Beijing as the study objects, the issues and characteristics of the water-soluble ions in fumes of coal fired boilers and theirs influence factors were analyzed and evaluated. The maximum mass concentration of total water-soluble ions in fumes of coal fired boilers in Beijing was 51.240 mg x m(-3) in the benchmark fume oxygen content, the minimum was 7.186 mg x m(-3), and the issues of the water-soluble ions were uncorrelated with the fume moisture content. SO4(2-) was the primary characteristic water-soluble ion for desulfurization reaction, and the rate of contribution of SO4(2-) in total water-soluble ions ranged from 63.8% to 81.0%. F- was another characteristic water-soluble ion in fumes of thermal power plant, and the rate of contribution of F- in total water-soluble ions ranged from 22.2% to 32.5%. The fume purification technologies significantly influenced the issues and the emission characteristics of water-soluble ions in fumes of coal fired boilers. Na+ was a characteristic water-soluble ion for the desulfurizer NaOH, NH4+ and NO3+ were characteristic for the desulfurizer NH4HCO3, and Mg2+ was characteristic for the desulfurizer MgO, but the Ca2+ emission was not increased by addition of the desulfurizer CaO or CaCO3 The concentrations of NH4+ and NO3- in fumes of thermal power plant were lower than those in fumes of industrial or heating coal fired boilers. The form of water-soluble ions was significantly correlated with fume temperature. The most water-soluble ions were in superfine state at higher fume temperature and were not easily captured by the filter membrane.

Some physicochemical aspects of water-soluble mineral flotation.

Science.gov (United States)

Wu, Zhijian; Wang, Xuming; Liu, Haining; Zhang, Huifang; Miller, Jan D

2016-09-01

Some physicochemical aspects of water-soluble mineral flotation including hydration phenomena, associations and interactions between collectors, air bubbles, and water-soluble mineral particles are presented. Flotation carried out in saturated salt solutions, and a wide range of collector concentrations for effective flotation of different salts are two basic aspects of water-soluble mineral flotation. Hydration of salt ions, mineral particle surfaces, collector molecules or ions, and collector aggregates play an important role in water-soluble mineral flotation. The adsorption of collectors onto bubble surfaces is suggested to be the precondition for the association of mineral particles with bubbles. The association of collectors with water-soluble minerals is a complicated process, which may include the adsorption of collector molecules or ions onto such surfaces, and/or the attachment of collector precipitates or crystals onto the mineral surfaces. The interactions between the collectors and the minerals include electrostatic and hydrophobic interactions, hydrogen bonding, and specific interactions, with electrostatic and hydrophobic interactions being the common mechanisms. For the association of ionic collectors with minerals with an opposite charge, electrostatic and hydrophobic interactions could have a synergistic effect, with the hydrophobic interactions between the hydrophobic groups of the previously associated collectors and the hydrophobic groups of oncoming collectors being an important attractive force. Association between solid particles and air bubbles is the key to froth flotation, which is affected by hydrophobicity of the mineral particle surfaces, surface charges of mineral particles and bubbles, mineral particle size and shape, temperature, bubble size, etc. The use of a collector together with a frother and the use of mixed surfactants as collectors are suggested to improve flotation. Copyright © 2016 Elsevier B.V. All rights reserved.

Prediction of the solubility of selected pharmaceuticals in water and alcohols with a group contribution method

International Nuclear Information System (INIS)

Pelczarska, Aleksandra; Ramjugernath, Deresh; Rarey, Jurgen; Domańska, Urszula

2013-01-01

Highlights: ► The prediction of solubility of pharmaceuticals in water and alcohols was presented. ► Improved group contribution method UNIFAC was proposed for 42 binary mixtures. ► Infinite activity coefficients were used in a model. ► A semi-predictive model with one experimental point was proposed. ► This model qualitatively describes the temperature dependency of Pharms. -- Abstract: An improved group contribution approach using activity coefficients at infinite dilution, which has been proposed by our group, was used for the prediction of the solubility of selected pharmaceuticals in water and alcohols [B. Moller, Activity of complex multifunctional organic compounds in common solvents, PhD Thesis, Chemical Engineering, University of KwaZulu-Natal, 2009]. The solubility of 16 different pharmaceuticals in water, ethanol and octan-1-ol was predicted over a fairly wide range of temperature with this group contribution model. The predicted values, along with values computed with the Schroeder-van Laar equation, are compared to experimental results published by us previously for 42 binary mixtures. The predicted solubility values were lower than those from the experiments for most of the mixtures. In order to improve the prediction method, a semi-predictive calculation using one experimental solubility value was implemented. This one point prediction has given acceptable results when comparison is made to experimental values

Effect of the structure, solid state and lipophilicity on the solubility of novel bicyclic derivatives

International Nuclear Information System (INIS)

Blokhina, Svetlana V.; Ol’khovich, Marina V.; Sharapova, Angelica V.; Volkova, Tatyana V.; Proshin, Alexey N.; Perlovich, German L.

2014-01-01

Highlights: • The solubility in buffer pH 7.4 of novel bicyclo-derivatives of amine were measured. • The influence of melting parameters and lipophilicity on the solubility was studied. • The thermodynamic parameters of the solubility process were calculated. - Abstract: Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer rH 7.4 has been measured within the range of (9.02 · 10 −5 to 1.05 · 10 −4 ) mol/l. The relationship between the chemical nature and the structure of the aryl substituents and the solubility parameter was investigated. The fusion temperatures, enthalpies and entropies have been determined experimentally. The influence of thermophysical characteristics and lipophilicity on the solubility was studied using regression analysis. The calculations by the solubility/lipophilicity equation showed an overall improvement of the predictions equal to 0.5 log units. It was concluded that the solvation has a considerable influence on the solubility of the compounds under consideration. It was also determined that the alkyl- and halogen-derivatives solubility values correlate with HYBOT descriptors characterizing the (donor + acceptor) properties of the substances. The thermodynamic parameters of the solubility process were calculated using the temperature dependences. The study also revealed that the solubility of the bicyclic compounds is characterized by high endothermicity of the processes and negative entropies

Crosslinked hydrogels?a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

OpenAIRE

Sun, Dajun D.; Lee, Ping I.

2014-01-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a ...

Optimization of translation profiles enhances protein expression and solubility.

Directory of Open Access Journals (Sweden)

Anne-Katrin Hess

Full Text Available mRNA is translated with a non-uniform speed that actively coordinates co-translational folding of protein domains. Using structure-based homology we identified the structural domains in epoxide hydrolases (EHs and introduced slow-translating codons to delineate the translation of single domains. These changes in translation speed dramatically improved the solubility of two EHs of metagenomic origin in Escherichia coli. Conversely, the importance of transient attenuation for the folding, and consequently solubility, of EH was evidenced with a member of the EH family from Agrobacterium radiobacter, which partitions in the soluble fraction when expressed in E. coli. Synonymous substitutions of codons shaping the slow-transiting regions to fast-translating codons render this protein insoluble. Furthermore, we show that low protein yield can be enhanced by decreasing the free folding energy of the initial 5'-coding region, which can disrupt mRNA secondary structure and enhance ribosomal loading. This study provides direct experimental evidence that mRNA is not a mere messenger for translation of codons into amino acids but bears an additional layer of information for folding, solubility and expression level of the encoded protein. Furthermore, it provides a general frame on how to modulate and fine-tune gene expression of a target protein.

Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions.

Science.gov (United States)

Wang, Dan; Li, Haiyan; Gu, Jingkai; Guo, Tao; Yang, Shuo; Guo, Zhen; Zhang, Xueju; Zhu, Weifeng; Zhang, Jiwen

2013-09-01

The purpose of this study was to simultaneously improve the solubility and stability of dihydroartemisinin (DHA) in aqueous solutions by a ternary cyclodextrin system comprised of DHA, hydroxypropyl-β-cyclodextrin (HP-β-CD) and a third auxiliary substance. Solubility and phase solubility studies were carried out to evaluate the solubilizing efficiency of HP-β-CD in association with various auxiliary substances. Then, the solid binary (DHA-HP-β-CD or DHA-lecithin) and ternary systems were prepared and characterized by Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD). The effect of the ternary system on the solubility, dissolution and stability of DHA in aqueous solutions was also investigated. As a result, the soybean lecithin was found to be the most promising third component in terms of solubility enhancement. For the solid characterization, the disappearance of the drug crystallinity indicated the formation of new solid phases, implicating the formation of the ternary system. The dissolution rate of the solid ternary system was much faster than that of the drug alone and binary systems. Importantly, compared with binary systems, the ternary system showed a significant improvement in the stability of DHA in Hank's balanced salt solutions (pH 7.4). The solubility and stability of DHA in aqueous solutions were simultaneously enhanced by the ternary system, which might be attributed to the possible formation of a ternary complex. For the ternary interactions, results of molecular docking studies further indicated that the lecithin covered the top of the wide rim of HP-β-CD and surrounded around the peroxide bridging of DHA, providing the possibility for the ternary complex formation. In summary, the ternary system prepared in our study, with simultaneous enhancement of DHA solubility and stability in aqueous solutions, might have an important pharmaceutical potential in the development of a better

Enhanced photocatalytic activity of nano titanium dioxide coated on ethanol-soluble carbon nanotubes

International Nuclear Information System (INIS)

Fu, Xiaofei; Yang, Hanpei; He, Kuanyan; Zhang, Yingchao; Wu, Junming

2013-01-01

Graphical abstract: Homogenous and dense spreading of TiO 2 on surface modified CNTs and improved photocatalytic performance of TiO 2 was achieved by coupling TiO 2 with ethanol-soluble CNTs. Display Omitted Highlights: ► Ethanol-soluble CNTs were acquired by surface modification. ► Enhanced photoactivity of TiO 2 coated on modified CNTs was obtained. ► Improved activity of TiO 2 is attributed to the intimate contact between TiO 2 and CNTs. ► Dense heterojunctions through Ti–O–CNTs at the interface is proposed. -- Abstract: Surface functionalized carbon nanotubes (CNTs) with ethanol solubility were synthesized and the CNTs–TiO 2 nanocomposites were prepared by coupling of TiO 2 with modified CNTs through a sol–gel method. The as-prepared CNTs and composites were characterized and the composite samples were evaluated for their photocatalytic activity toward the degradation of aqueous methyl orange. It is showed that the acid oxidation of CNTs leads to the embedding of oxygenated functional groups, and as a result, the acid-treated CNTs in turn may serve as chemical reactors for subsequent covalent grafting of octadecylamine. Improved photocatalytic performance of CNTs–TiO 2 composites was obtained, which is mainly attributed to the high dispersion of TiO 2 on ethanol-soluble CNTs and the intimate contact between TiO 2 and CNTs resulted from the dense heterojunctions through the Ti-O-C structure at the interface between TiO 2 and CNTs.

Thermodynamic Solubility Profile of Carbamazepine-Cinnamic Acid Cocrystal at Different pH.

Science.gov (United States)

Keramatnia, Fatemeh; Shayanfar, Ali; Jouyban, Abolghasem

2015-08-01

Pharmaceutical cocrystal formation is a direct way to dramatically influence physicochemical properties of drug substances, especially their solubility and dissolution rate. Because of their instability in the solution, thermodynamic solubility of cocrystals could not be determined in the common way like other compounds; therefore, the thermodynamic solubility is calculated through concentration of their components in the eutectic point. The objective of this study is to investigate the effect of an ionizable coformer in cocrystal with a nonionizable drug at different pH. Carbamazepine (CBZ), a nonionizable drug with cinnamic acid (CIN), which is an acidic coformer, was selected to prepare CBZ-CIN cocrystal and its thermodynamic solubility was studied in pH range 2-7. Instead of HPLC that is a costly and time-consuming method, a chemometric-based approach, net analyte signal standard addition method, was selected for simultaneous determination of CBZ and CIN in solution. The result showed that, as pH increases, CIN ionization leads to change in CBZ-CIN cocrystal solubility and stability in solution. In addition, the results of this study indicated that there is no significant difference between intrinsic solubility of CBZ and cocrystal despite the higher ideal solubility of cocrystal. This verifies that ideal solubility is not good parameter to predict cocrystal solubility. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Modulation of solubility and dissolution of furosemide by preparation of phospholipid complex

OpenAIRE

Mona Semalty; Prateeksha Badoni; Devendra Singh; Ajay Semalty

2014-01-01

Aim: The aim of this study is to improve the solubility and dissolution of furosemide (a potent high ceiling diuretic used for the treatment of hypertension and a Class IV drug that is low solubility and low permeability drug as per the Biopharmaceutical Classification System) by preparing its phospholipid complexes or pharmacosomes. Materials and Methods: Furosemide was complexed with phosphatidylcholine in four different molar ratios (1:1, 1:2, 1:3 and 1:4) by conventional solvent-evaporati...

β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs

DEFF Research Database (Denmark)

Di Cagno, Massimiliano; Nielsen, Thorbjørn Terndrup; Lambertsen Larsen, Kim

2014-01-01

The aim of this work was to assess the potential of β-cyclodextrin (β-CD)-dextran polymers for drug delivery, in terms of molecular mass, the complexation reaction mechanism using a model drug, and solubilization efficiency for examples of poorly soluble model drugs. For this purpose size analysis...... of different β-CD-dextrans was carried out by both size exclusion chromatography (SEC) and flow field-flow fractionation (FFF). All investigated polymers were of appropriate sizes for potential parenteral administration. Mass/mass percentage ratio between β-CD units and dextran backbones where measured by both...... of solubilization efficiencies, phase-solubility diagrams where made employing two poorly soluble model drugs, one dissociating (ibuprofen, IBP) and one pH independent (hydrocortisone, HC). Thermodynamic results demonstrated that the presence of the dextran-back bone structure improves complexation efficiency...

Solubility of cobalt in primary circuit solutions

International Nuclear Information System (INIS)

Lambert, I.; Joyer, F.

1992-01-01

The solubility of cobalt ferrite (CoFe 2 O 4 ) was measured in PWR primary circuit conditions, in the temperature range 250-350 deg C, and the results were compared with the ones obtained on magnetite and nickel ferrite. As in the former cases, it was found that, in the prevailing primary circuit conditions, the solubility of the cobalt ferrite was minimum at temperatures around 300 deg C, for cobalt as well as for iron. The equilibrium iron concentration is significantly lower than in the case of magnetite. The results are discussed in relation with the POTHY code, based only on thermodynamic laws and data, used for the prediction of the primary circuit chemistry

The Solubility Parameters of Ionic Liquids

Science.gov (United States)

Marciniak, Andrzej

2010-01-01

The Hildebrand’s solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated. PMID:20559495

The Solubility Parameters of Ionic Liquids

Directory of Open Access Journals (Sweden)

Andrzej Marciniak

2010-04-01

Full Text Available The Hildebrand’s solubility parameters have been calculated for 18 ionic liquids from the inverse gas chromatography measurements of the activity coefficients at infinite dilution. Retention data were used for the calculation. The solubility parameters are helpful for the prediction of the solubility in the binary solvent mixtures. From the solubility parameters, the standard enthalpies of vaporization of ionic liquids were estimated.

Solubility of sparingly soluble drug derivatives of anthranilic acid.

Science.gov (United States)

Domańska, Urszula; Pobudkowska, Aneta; Pelczarska, Aleksandra

2011-03-24

This work is a continuation of our systematic study of the solubility of pharmaceuticals (Pharms). All substances here are derivatives of anthranilic acid, and have an anti-inflammatory direction of action (niflumic acid, flufenamic acid, and diclofenac sodium). The basic thermal properties of pure Pharms, i.e., melting and glass-transition temperatures as well as the enthalpy of melting, have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The equilibrium mole fraction solubilities of three pharmaceuticals were measured in a range of temperatures from 285 to 355 K in three important solvents for Pharm investigations: water, ethanol, and 1-octanol using a dynamic method and spectroscopic UV-vis method. The experimental solubility data have been correlated by means of the commonly known G(E) equation: the NRTL, with the assumption that the systems studied here have revealed simple eutectic mixtures. pK(a) precise measurement values have been investigated with the Bates-Schwarzenbach spectrophotometric method. © 2011 American Chemical Society

Tetrasubstituted phenanthrolines as highly potent, water-soluble, and selective g-quadruplex ligands

DEFF Research Database (Denmark)

Larsen, Anders Foller; Nielsen, Mads Corvinius; Ulven, Trond

2012-01-01

Small molecules capable of stabilizing the G-quadruplex (G4) structure are of interest for the development of improved anticancer drugs. Novel 4,7-diamino-substituted 1,10-phenanthroline-2,9-dicarboxamides that represent hybrid structures of known phenanthroline-based ligands have been designed....... An efficient synthetic route to the compounds has been developed and their interactions with various G4 sequences have been evaluated by Förster resonance energy transfer (FRET) melting assays, fluorescent intercalator displacement (FID), electrospray ionization mass spectrometry (ESI-MS), and circular...... dichroism (CD) spectroscopy. The preferred compounds have high aqueous solubility and are strong and potent G4 binders with a high selectivity over duplex DNA; thus, they represent a significant improvement over the lead compounds. Two of the compounds are inhibitors of HeLa and HT1080 cell proliferation....

Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid.

Science.gov (United States)

Miwa, Yasushi; Hamamoto, Hidetoshi; Ishida, Tatsuhiro

2016-05-01

Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac alone patch, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine alone patch. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical Methods for the Determination of Soluble and Insoluble Non-Starch Polysaccharides - Review

Directory of Open Access Journals (Sweden)

Rodica Căpriţă

2011-10-01

Full Text Available Polysaccharides are macromolecules of monosaccharides linked by glycosidic bonds. Non-starch polysaccharides(NSP are principally non-α-glucan polysaccharides of the plant cell wall. They are a heterogeneous group ofpolysaccharides with varying degrees of water solubility, size, and structure. The water insoluble fiber fractioninclude cellulose, galactomannans, xylans, xyloglucans, and lignin, while the water-soluble fibers are the pectins,arabinogalactans, arabinoxylans, and β-(1,3(1,4-D-glucans (β-glucans. Both the enzymatic-gravimetric andenzymatic-chemical methods used for the determination of soluble and insoluble non-starch polysaccharides haveundergone a number of modifications and improvements, most occurring over the last 20 years.

On the solubility of yttrium in RuO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Music, Denis; Zumdick, Naemi A.; Hallstedt, Bengt; Schneider, Jochen M. [Materials Chemistry, RWTH Aachen University, D-52056 Aachen (Germany)

2011-09-01

We have investigated the solubility of Y in rutile RuO{sub 2} using experimental and theoretical methods. Nanostructured Ru-Y-O thin films were synthesized via combinatorial reactive sputtering with an O/metal ratio of 2.6 and a Y content of 0.3 to 12.6 at. %. A solubility limit of 1.7 at. % was identified using x-ray photoelectron spectroscopy and x-ray diffraction. Based on ab initio and thermodynamic modeling, the solubility of Y can be understood. Smaller Y amounts are incorporated into the lattice, forming a metastable film, with local structural deformations due to size effects. As the Y content is increased, extensive local structural deformations are observed, but phase separation does not occur due to kinetic limitations. Nanostructured RuO{sub 2} alloyed with Y might lead to enhanced phonon scattering and quantum confinement effects, which in turn improve the thermoelectric efficiency.

Intestinal absorption of water-soluble vitamins in health and disease

OpenAIRE

Said, Hamid M.

2011-01-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth an...

Solubility of simulated PWR primary circuit corrosion products

International Nuclear Information System (INIS)

Kunig, R.H.; Sandler, Y.L.

1986-08-01

The solubility behavior of non-stoichiometric nickel ferrites, nickel-cobalt ferrites, and magnetite, as model substances for the corrosion products (''crud'') formed in nuclear pressurized water reactors, was studied in a flow system in aqueous solutions of lithium hydroxide, boric acid, and hydrogen with pH, temperature, and hydrogen concentrations as parameters. Below the temperature region of 300 to 330 0 C, at hydrogen concentrations of 25 to 40 cm 3 /kg H 2 O as used during reactor operation, the solubility of nickel-cobalt ferrite is the same as that of Ni and Co/sub x/Fe/sub 3-x/O 4 (x 3 /kg of hydrogen, the equilibrium iron and nickel solubilities increase congruently down to about 100 0 C, in a manner consistent with the solubility of Fe 3 O 4 , but sharply decline at lower temperatures, apparently due to formation of a borated layer. A cooldown experiment on a time scale of a typical Westinghouse reactor shutdown, as well as static experiments carried out on various ferrite samples at 60 0 C show that after addition of oxygen or peroxide evolution of nickel (and possibly cobalt) above the equilibrium solubility in hydrogen depends on the presence of dissociation products prior to oxidation. Thermodynamic calculations of various reduction and oxidative decomposition reactions for stoichiometric and non-stoichiometric nickel ferrite and cobalt ferrite are presented. Their significance to evolutions of nickel and cobalt on reactor shutdown is discussed. 30 refs., 38 figs., 34 tabs

Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

Science.gov (United States)

Nawawi, H; Osman, N S; Annuar, R; Khalid, B A K; Yusoff, K

2003-08-01

Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.

Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying.

Science.gov (United States)

Meng, Jian; Zheng, Liangyuan

2007-09-01

Self-microemulsifying drug delivery systems (SMEDDS) are useful to improve the bioavailability of poorly water-soluble drugs by increasing their apparent solubility through solubilization. However, very few studies, to date, have systematically examined the level of drug apparent solubility in o/w microemulsion formed by self-microemulsifying. In this study, a mixture experimental design was used to simulate the influence of the compositions on simvastatin apparent solubility quantitatively through an empirical model. The reduced cubic polynomial equation successfully modeled the evolution of simvastatin apparent solubility. The results were presented using an analysis of response surface showing a scale of possible simvastatin apparent solubility between 0.0024 ~ 29.0 mg/mL. Moreover, this technique showed that simvastatin apparent solubility was mainly influenced by microemulsion concentration and, suggested that the drug would precipitate in the gastrointestinal tract due to dilution by gastrointestinal fluids. Furthermore, the model would help us design the formulation to maximize the drug apparent solubility and avoid precipitation of the drug.

Solubility of Carbon in Nanocrystalline -Iron

OpenAIRE

Alexander Kirchner; Bernd Kieback

2012-01-01

A thermodynamic model for nanocrystalline interstitial alloys is presented. The equilibrium solid solubility of carbon in -iron is calculated for given grain size. Inside the strained nanograins local variation of the carbon content is predicted. Due to the nonlinear relation between strain and solubility, the averaged solubility in the grain interior increases with decreasing grain size. The majority of the global solubility enhancement is due to grain boundary enrichment however. Therefor...

An Improved Variant of Soybean Type 1 Diacylglycerol Acyltransferase Increases the Oil Content and Decreases the Soluble Carbohydrate Content of Soybeans[OPEN

Science.gov (United States)

Shen, Bo; Damude, Howard G.; Everard, John D.; Booth, John R.

2016-01-01

Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae. Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm. Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans. PMID:27208257

Intrinsic solubility estimation and pH-solubility behavior of cosalane (NSC 658586), an extremely hydrophobic diprotic acid.

Science.gov (United States)

Venkatesh, S; Li, J; Xu, Y; Vishnuvajjala, R; Anderson, B D

1996-10-01

The selection of cosalane (NSC 658586) by the National Cancer Institute for further development as a potential drug candidate for the treatment of AIDS led to the exploration of the solubility behavior of this extremely hydrophobic drug, which has an intrinsic solubility (S0 approaching 1 ng/ml. This study describes attempts to reliably measure the intrinsic solubility of cosalane and examine its pH-solubility behavior. S0 was estimated by 5 different strategies: (a) direct determination in an aqueous suspension: (b) facilitated dissolution; (c) estimation from the octanol/water partition coefficient and octanol solubility (d) application of an empirical equation based on melting point and partition coefficient; and (e) estimation from the hydrocarbon solubility and functional group contributions for transfer from hydrocarbon to water. S0 estimates using these five methods varied over a 5 x 107-fold range Method (a) yielded the highest values, two-orders of magnitude greater than those obtained by method (b) (facilitated dissolution. 1.4 +/- 0.5 ng/ml). Method (c) gave a value 20-fold higher while that from method (d) was in fair agreement with that from facilitated dissolution. Method (e) yielded a value several orders-of-magnitude lower than other methods. A molecular dynamics simulation suggests that folded conformations not accounted for by group contributions may reduce cosalane's effective hydrophobicity. Ionic equilibria calculations for this weak diprotic acid suggested a 100-fold increase in solubility per pH unit increase. The pH-solubility profile of cosalane at 25 degrees C agreed closely with theory. These studies highlight the difficulty in determining solubility of very poorly soluble compounds and the possible advantage of the facilitated dissolution method. The diprotic nature of cosalane enabled a solubility enhancement of > 107-fold by simple pH adjustment.

The solubility of carbon dioxide in aqueous N-methyldiethanolamine solutions

NARCIS (Netherlands)

Huttenhuis, P. J. G.; Agrawal, N. J.; Solbraa, E.; Versteeg, G. F.

2008-01-01

In this study the electrolyte equation of state as proposed by Solbraa [E. Solbraa, Equilibrium and non-equilibrium thermodynamics of natural gas processing, Ph.D. thesis Norwegian University of Science and Technology, 2002] was systematically studied and improved to describe the solubility of

Evaluation of drug-polymer solubility curves through formal statistical analysis

DEFF Research Database (Denmark)

Knopp, Matthias Manne; Olesen, Niels Erik; Holm, Per

2015-01-01

drying or potentially film casting (if experimental reproducibility can be improved) should be used to prepare the amorphous dispersions when performing solubility measurements of this kind. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:44-51, 2015....

The solubility of uranium in cementitious near-field chemical conditions

Energy Technology Data Exchange (ETDEWEB)

Baston, G.M.N.; Brownsword, M.; Cross, J.E.; Hobley, J.; Moreton, A.D.; Smith-Briggs, J.L.; Thomason, H.P. [AEA Decommissioning and Waste Management, Harwell (United Kingdom)

1993-05-01

Tetravalent and hexavalent uranium solubilities have been measured in cement-equilibriated water for pH values from 4 to 13. Tetravalent uranium solubilities at pH 12 have been measured by three experimental techniques: oversaturation, undersaturation and by the use of an electrochemical cell which controlled the redox conditions. The experimentally obtained data have been simulated using the thermodynamic equilibrium program HARPHRQ in conjunction with three different sets of thermodynamic data for uranium. In each case, differences were found between the predicted and measured uranium behaviour. For hexavalent uranium at high pH values the model suggested the formation of anionic hydrolysis products which led to the prediction of uranium solubilities significantly higher than those observed. Refinement of the thermodynamic data used in the model enabled the derivation of maximum values for the formation constants of these species under cementitious conditions. Similarly, the experimental data have been used to refine a model of tetravalent uranium solubility under cementitious near-field conditions. (author).

The solubility of uranium in cementitious near-field chemical conditions

International Nuclear Information System (INIS)

Baston, G.M.N.; Brownsword, M.; Cross, J.E.; Hobley, J.; Moreton, A.D.; Smith-Briggs, J.L.; Thomason, H.P.

1993-05-01

Tetravalent and hexavalent uranium solubilities have been measured in cement-equilibriated water for pH values from 4 to 13. Tetravalent uranium solubilities at pH 12 have been measured by three experimental techniques: oversaturation, undersaturation and by the use of an electrochemical cell which controlled the redox conditions. The experimentally obtained data have been simulated using the thermodynamic equilibrium program HARPHRQ in conjunction with three different sets of thermodynamic data for uranium. In each case, differences were found between the predicted and measured uranium behaviour. For hexavalent uranium at high pH values the model suggested the formation of anionic hydrolysis products which led to the prediction of uranium solubilities significantly higher than those observed. Refinement of the thermodynamic data used in the model enabled the derivation of maximum values for the formation constants of these species under cementitious conditions. Similarly, the experimental data have been used to refine a model of tetravalent uranium solubility under cementitious near-field conditions. (author)

Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin.

Science.gov (United States)

Fatima, Munazza T; Chanchal, Abhishek; Yavvari, Prabhu S; Bhagat, Somnath D; Gujrati, Mansi; Mishra, Ram K; Srivastava, Aasheesh

2016-07-11

Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their

On the americium oxalate solubility

International Nuclear Information System (INIS)

Zakolupin, S.A.; Korablin, Eh.V.

1977-01-01

The americium oxalate solubility at different nitric (0.0-1 M) and oxalic (0.0-0.4 M) acid concentrations was investigated in the temperature range from 14 to 60 deg C. The dependence of americium oxalate solubility on the oxalic acid concentration was determined. Increasing oxalic acid concentration was found to reduce the americium oxalate solubility. The dependence of americium oxalate solubility on the oxalic acid concentration was noted to be a minimum at low acidity (0.1-0.3 M nitric acid). This is most likely due to Am(C 2 O 4 ) + , Am(C 2 O 4 ) 2 - and Am(C 2 O 4 ) 3 3- complex ion formation which have different unstability constants. On the basis of the data obtained, a preliminary estimate was carried out for the product of americium oxalate solubility in nitric acid medium (10 -29 -10 -31 ) and of the one in water (6.4x10 -20 )

Inhaler Reminders Significantly Improve Asthma Patients' Use of Controller Medications

Science.gov (United States)

... controller medications Share | Inhaler reminders significantly improve asthma patients’ use of controller medications Published Online: July 22, ... the burden and risk of asthma, but many patients do not use them regularly. This poor adherence ...

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods

Science.gov (United States)

Boaz, Segal M.; Champagne, Cory D.; Fowler, Melinda A.; Houser, Dorian H.; Crocker, Daniel E.

2011-01-01

Despite the importance of water-soluble vitamins to metabolism, there is limited knowledge of their serum availability in fasting wildlife. We evaluated changes in water-soluble vitamins in northern elephant seals, a species with an exceptional ability to withstand nutrient deprivation. We used a metabolomics approach to measure vitamins and associated metabolites under extended natural fasts for up to seven weeks in free-ranging lactating or developing seals. Water-soluble vitamins were not detected with this metabolomics platform, but could be measured with standard assays. Concentrations of measured vitamins varied independently, but all were maintained at detectable levels over extended fasts, suggesting that defense of vitamin levels is a component of fasting adaptation in the seals. Metabolomics was not ideal for generating complete vitamin profiles in this species, but gave novel insights into vitamin metabolism by detecting key related metabolites. For example, niacin level reductions in lactating females were associated with significant reductions in precursors suggesting downregulation of the niacin synthetic pathway. The ability to detect individual vitamins using metabolomics may be impacted by the large number of novel compounds detected. Modifications to the analysis platforms and compound detection algorithms used in this study may be required for improving water-soluble vitamin detection in this and other novel wildlife systems. PMID:21983145

Atmospheric Processing of Volcanic Glass: Effects on Iron Solubility and Redox Speciation.

Science.gov (United States)

Maters, Elena C; Delmelle, Pierre; Bonneville, Steeve

2016-05-17

Volcanic ash from explosive eruptions can provide iron (Fe) to oceanic regions where this micronutrient limits primary production. Controls on the soluble Fe fraction in ash remain poorly understood but Fe solubility is likely influenced during atmospheric transport by condensation-evaporation cycles which induce large pH fluctuations. Using glass powder as surrogate for ash, we experimentally simulate its atmospheric processing via cycles of pH 2 and 5 exposure. Glass fractional Fe solubility (maximum 0.4%) is governed by the pH 2 exposure duration rather than by the pH fluctuations, however; pH 5 exposure induces precipitation of Fe-bearing nanoparticles which (re)dissolve at pH 2. Glass leaching/dissolution release Fe(II) and Fe(III) which are differentially affected by changes in pH; the average dissolved Fe(II)/Fetot ratio is ∼0.09 at pH 2 versus ∼0.18 at pH 5. Iron release at pH 2 from glass with a relatively high bulk Fe(II)/Fetot ratio (0.5), limited aqueous Fe(II) oxidation at pH 5, and possibly glass-mediated aqueous Fe(III) reduction may render atmospherically processed ash a significant source of Fe(II) for phytoplankton. By providing new insight into the form(s) of Fe associated with ash as wet aerosol versus cloud droplet, we improve knowledge of atmospheric controls on volcanogenic Fe delivery to the ocean.

Enhancement of solubility and dissolution rate of atorvastatin ...

African Journals Online (AJOL)

solvent evaporation method using methanol. ... crystal significantly increases in solubility with a dissolution rate 2 - 3 times faster than that of ... considered one of the most effective synthetic .... temperature of 37 ± 0.5 °C. The test was carried.

Nootkatone encapsulation by cyclodextrins: Effect on water solubility and photostability.

Science.gov (United States)

Kfoury, Miriana; Landy, David; Ruellan, Steven; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

2017-12-01

Nootkatone (NO) is a sesquiterpenoid volatile flavor, used in foods, cosmetics and pharmaceuticals, possessing also insect repellent activity. Its application is limited because of its low aqueous solubility and stability; this could be resolved by encapsulation in cyclodextrins (CDs). This study evaluated the encapsulation of NO by CDs using phase solubility studies, Isothermal Titration Calorimetry, Nuclear Magnetic Resonance spectroscopy and molecular modeling. Solid CD/NO inclusion complex was prepared and characterized for encapsulation efficiency and loading capacity using UV-Visible. Thermal properties were investigated by thermogravimetric-differential thermal analysis and release studies were performed using multiple headspace extraction. Formation constants (K f ) proved the formation of stable inclusion complexes. NO aqueous solubility, photo- and thermal stability were enhanced and the release could be insured from solid complex in aqueous solution. This suggests that CDs are promising carrier to improve NO properties and, consequently, to enlarge its use in foods, cosmetics, pharmaceuticals and agrochemicals preparations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.

Science.gov (United States)

Rouxhet, L; Dinguizli, M; Latere Dwan'isa, J P; Ould-Ouali, L; Twaddle, P; Nathan, A; Brewster, M E; Rosenblatt, J; Ariën, A; Préat, V

2009-12-01

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.

Formulation of a Novel Nano emulsion System for Enhanced Solubility of a Sparingly Water Soluble Antibiotic, Clarithromycin

International Nuclear Information System (INIS)

Vatsraj, S.; Pathak, H.; Chauhan, K.

2014-01-01

The sparingly water soluble property of majority of medicinally significant drugs acts as a potential barrier towards its utilization for therapeutic purpose. The present study was thus aimed at development of a novel oil-in-water (o/w) nano emulsion (NE) system having ability to function as carrier for poorly soluble drugs with clarithromycin as a model antibiotic. The therapeutically effective concentration of clarithromycin, 5 mg/mL, was achieved using polysorbate 80 combined with olive oil as lipophilic counterion. A three-level three-factorial central composite experimental design was utilized to conduct the experiments. The effects of selected variables, polysorbate 80 and olive oil content and concentration of polyvinyl alcohol, were investigated. The particle size of clarithromycin for the optimized formulation was observed to be 30 nm. The morphology of the nano emulsion was explored using transmission electron microscopy (TEM). The emulsions prepared with the optimized formula demonstrated good physical stability during storage at room temperature. Antibacterial activity was conducted with the optimized nano emulsion NESH 01 and compared with free clarithromycin. Zone of inhibition was larger for NESH 01 as compared to that with free clarithromycin. This implies that the solubility and hence the bioavailability of clarithromycin has increased in the formulated nano emulsion system.

Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro

International Nuclear Information System (INIS)

McNeilly, Jane D.; Heal, Mathew R.; Beverland, Iain J.; Howe, Alan; Gibson, Mark D.; Hibbs, Leon R.; MacNee, William; Donaldson, Ken

2004-01-01

Epidemiological studies have consistently reported a higher incidence of respiratory illnesses such as bronchitis, metal fume fever (MFF), and chronic pneumonitis among welders exposed to high concentrations of metal-enriched welding fumes. Here, we studied the molecular toxicology of three different metal-rich welding fumes: NIMROD 182, NIMROD c276, and COBSTEL 6. Fume toxicity in vitro was determined by exposing human type II alveolar epithelial cell line (A549) to whole welding fume, a soluble extract of fume or the 'washed' particulate. All whole fumes were significantly toxic to A549 cells at doses >63 μg ml -1 (TD 50; 42, 25, and 12 μg ml -1 , respectively). NIMROD c276 and COBSTEL 6 fumes increased levels of IL-8 mRNA and protein at 6 h and protein at 24 h, as did the soluble fraction alone, whereas metal chelation of the soluble fraction using chelex beads attenuated the effect. The soluble fraction of all three fumes caused a rapid depletion in intracellular glutathione following 2-h exposure with a rebound increase by 24 h. In addition, both nickel based fumes, NIMROD 182 and NIMROD c276, induced significant reactive oxygen species (ROS) production in A549 cells after 2 h as determined by DCFH fluorescence. ICP analysis confirmed that transition metal concentrations were similar in the whole and soluble fractions of each fume (dominated by Cr), but significantly less in both the washed particles and chelated fractions. These results support the hypothesis that the enhanced pro-inflammatory responses of welding fume particulates are mediated by soluble transition metal components via an oxidative stress mechanism

Amelioration of radiation induced oxidative stress using water soluble chitosan produced by Aspergillus niger

International Nuclear Information System (INIS)

EL-Sonbaty, S.M.; Swailam, H.M.; Noaman, E.

2012-01-01

Chitosan is a natural polysaccharide synthesized by a great number of living organisms and considered as a source of potential bioactive material and has many biological applications which are greatly affected by its solubility in neutral ph. In this study low molecular weight water soluble chitosan was prepared by chemical degradation of chitosan produced by Aspergillus niger using H 2 O 2 . Chitosan chemical structure was detected before and after treatment using FTIR spectrum, and its molecular weight was determined by its viscosity using viscometer. Its antioxidant activity against gamma radiation was evaluated in vivo using rats. Rats were divided into 4 groups; group 1: control, group 2: exposed to acute dose of gamma radiation (6 Gy), group 3: received water soluble chitosan, group 4: received water soluble chitosan then exposed to gamma radiation as group 2. Gamma radiation significantly increased malonaldehyde, decreased glutathione concentration, activity of superoxide dismutase, catalase, and glutatione peroxidase, while significantly increase the activity of alanine transferase, aspartate transferase, urea and creatinine concentration. Administration of water soluble chitosan has ameliorated induced changes caused by gamma radiation. It could be concluded that water soluble chitosan by scavenging free radicals directly or indirectly may act as a potent radioprotector against ionizing irradiation.

Data representing two separate LC-MS methods for detection and quantification of water-soluble and fat-soluble vitamins in tears and blood serum

Directory of Open Access Journals (Sweden)

Maryam Khaksari

2017-04-01

Full Text Available Two separate liquid chromatography (LC-mass spectrometry (MS methods were developed for determination and quantification of water-soluble and fat-soluble vitamins in human tear and blood serum samples. The water-soluble vitamin method was originally developed to detect vitamins B1, B2, B3 (nicotinamide, B5, B6 (pyridoxine, B7, B9 and B12 while the fat-soluble vitamin method detected vitamins A, D3, 25(OHD3, E and K1. These methods were then validated with tear and blood serum samples. In this data in brief article, we provide details on the two LC-MS methods development, methods sensitivity, as well as precision and accuracy for determination of vitamins in human tears and blood serum. These methods were then used to determine the vitamin concentrations in infant and parent samples under a clinical study which were reported in "Determination of Water-Soluble and Fat-Soluble Vitamins in Tears and Blood Serum of Infants and Parents by Liquid Chromatography/Mass Spectrometry DOI:10.1016/j.exer.2016.12.007 [1]". This article provides more details on comparison of vitamin concentrations in the samples with the ranges reported in the literature along with the medically accepted normal ranges. The details on concentrations below the limits of detection (LOD and limits of quantification (LOQ are also discussed. Vitamin concentrations were also compared and cross-correlated with clinical data and nutritional information. Significant differences and strongly correlated data were reported in [1]. This article provides comprehensive details on the data with slight differences or slight correlations.

Data representing two separate LC-MS methods for detection and quantification of water-soluble and fat-soluble vitamins in tears and blood serum.

Science.gov (United States)

Khaksari, Maryam; Mazzoleni, Lynn R; Ruan, Chunhai; Kennedy, Robert T; Minerick, Adrienne R

2017-04-01

Two separate liquid chromatography (LC)-mass spectrometry (MS) methods were developed for determination and quantification of water-soluble and fat-soluble vitamins in human tear and blood serum samples. The water-soluble vitamin method was originally developed to detect vitamins B 1 , B 2 , B 3 (nicotinamide), B 5 , B 6 (pyridoxine), B 7 , B 9 and B 12 while the fat-soluble vitamin method detected vitamins A, D 3 , 25(OH)D 3, E and K 1 . These methods were then validated with tear and blood serum samples. In this data in brief article, we provide details on the two LC-MS methods development, methods sensitivity, as well as precision and accuracy for determination of vitamins in human tears and blood serum. These methods were then used to determine the vitamin concentrations in infant and parent samples under a clinical study which were reported in "Determination of Water-Soluble and Fat-Soluble Vitamins in Tears and Blood Serum of Infants and Parents by Liquid Chromatography/Mass Spectrometry DOI:10.1016/j.exer.2016.12.007 [1]". This article provides more details on comparison of vitamin concentrations in the samples with the ranges reported in the literature along with the medically accepted normal ranges. The details on concentrations below the limits of detection (LOD) and limits of quantification (LOQ) are also discussed. Vitamin concentrations were also compared and cross-correlated with clinical data and nutritional information. Significant differences and strongly correlated data were reported in [1]. This article provides comprehensive details on the data with slight differences or slight correlations.

The effects of disordered structure on the solubility and dissolution rates of some hydrophilic, sparingly soluble drugs.

Science.gov (United States)

Mosharraf, M; Sebhatu, T; Nyström, C

1999-01-15

The effects of experimental design on the apparent solubility of two sparingly soluble hydrophilic compounds (barium sulphate and calcium carbonate) were studied in this paper. The apparent solubility appeared to be primarily dependent on the amount of solute added to the solvent in each experiment, increasing with increased amounts. This effect seems to be due to the existence of a peripheral disordered layer. However physico-chemical methods used in the present study were not able to unambiguously verify the existence of any disorder in the solid state structure of the drugs. At higher proportions of solute to solvent, the solubility reached a plateau corresponding to the solubility of the disordered or amorphous molecular form of the material. Milling the powders caused the plateau to be reached at lower proportions of solute to solvent, since this further disordered the surface of the drug particles. It was also found that the apparent solubility of the drugs tested decreased after storage at high relative humidities. A model for describing the effects of a disordered surface layer of varying thickness and continuity on the solubility of a substance is presented. This model may be used as a method for detection of minute amount of disorder, where no other technique is capable of detecting the disordered structure. It is suggested that recrystallisation of the material occurs via slow solid-state transition at the surface of the drug particle; this would slowly reduce the apparent solubility of the substance at the plateau level to the thermodynamically stable value. A biphasic dissolution rate profile was obtained. The solubility of the disordered surface of the particles appeared to be the rate-determining factor during the initial dissolution phase, while the solubility of the crystalline core was the rate-determining factor during the final slower phase.

Determination of radionuclide solubility limits to be used in SR 97. Uncertainties associated to calculated solubilities

Energy Technology Data Exchange (ETDEWEB)

Bruno, J.; Cera, E.; Duro, L.; Jordana, S. [QuantiSci S.L., Barcelona (Spain); Pablo, J. de [DEQ-UPC, Barcelona (Spain); Savage, D. [QuantiSci Ltd., Henley-on-Thames (United Kingdom)

1997-12-01

The thermochemical behaviour of 24 critical radionuclides for the forthcoming SR97 PA exercise is discussed. The available databases are reviewed and updated with new data and an extended database for aqueous and solid species of the radionuclides of interest is proposed. We have calculated solubility limits for the radionuclides of interest under different groundwater compositions. A sensitivity analysis of the calculated solubilities with the composition of the groundwater is presented. Besides selecting the most likely solubility limiting phases, in this work we have used coprecipitation approaches in order to calculate more realistic solubility limits for minor radionuclides, such as Ra, Am and Cm. The comparison between the calculated solubilities and the concentrations measured in relevant natural systems (NA) and in spent fuel leaching experiments helps to assess the validity of the methodology used and to derive source term concentrations for the radionuclides studied. The uncertainties associated to the solubilities of the main radionuclides involved in the spent nuclear fuel have also been discussed in this work. The variability of the groundwater chemistry; redox conditions and temperature of the system have been considered the main factors affecting the solubilities. In this case, a sensitivity analysis has been performed in order to study solubility changes as a function of these parameters. The uncertainties have been calculated by including the values found in a major extent in typical granitic groundwaters. The results obtained from this analysis indicate that there are some radionuclides which are not affected by these parameters, i.e. Ag, Cm, Ho, Nb, Ni, Np, Pu, Se, Sm, Sn, Sr, Tc and U

Chitosan cocrystals embedded alginate beads for enhancing the solubility and bioavailability of aceclofenac.

Science.gov (United States)

Ganesh, Mani; Jeon, Ung Jin; Ubaidulla, Udhumansha; Hemalatha, Pushparaj; Saravanakumar, Arthanari; Peng, Mei Mei; Jang, Hyun Tae

2015-03-01

Enhanced oral bioavailability of aceclofenac has been achieved using chitosan cocrystals of aceclofenac and its entrapment into alginate matrix a super saturated drug delivery system (SDDS). Prepared SDDS were evaluated by various physiochemical and pharmacological methods. The result revealed that the primary cocrystals enhanced the solubility of the drug and the thick gelled polymer matrix that formed from swelling of calcium alginate beads makes it to release the drug in continuous and sustained manner by supersaturated drug diffusion. The Cmax, Tmax and relative bioavailability for aceclofenac cocrystal and aceclofenac SDDS were 2.06±0.42 μg/ml, 1 h, 159.72±10.84 and 2.01 μg/ml, 1 h, 352.76±12.91, respectively. Anti-inflammatory activity of aceclofenac was significantly improved with the SDDS. With respect to the results, it revealed that the SDDS described herein might be a promising tool for the oral sustained release of aceclofenac and likely for that of various other poorly soluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Retrograde curves of solidus and solubility

International Nuclear Information System (INIS)

Vasil'ev, M.V.

1979-01-01

The investigation was concerned with the constitutional diagrams of the eutectic type with ''retrograde solidus'' and ''retrograde solubility curve'' which must be considered as diagrams with degenerate monotectic transformation. The solidus and the solubility curves form a retrograde curve with a common retrograde point representing the solubility maximum. The two branches of the Aetrograde curve can be described with the aid of two similar equations. Presented are corresponding equations for the Cd-Zn system and shown is the possibility of predicting the run of the solubility curve

Solubility of {beta}-carotene in ethanol- and triolein-modified CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Araus, Karina A. [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Canales, Roberto I. [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Valle, Jose M. del [Departamento de Ingenieria Quimica y Bioprocesos, Pontificia Universidad Catolica de Chile, Avda. Vicuna Mackenna 4860, Macul, Santiago (Chile); Fuente, Juan C. de la, E-mail: juan.delafuente@usm.cl [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Centro Regional de Estudios en Alimentos Saludables, Blanco 1623, Valparaiso (Chile)

2011-12-15

Highlights: > We measure solubility of {beta}-carotene in pure CO{sub 2}, and with ethanol and triolein as co-solvents. > We model the solubility of {beta}-carotene in pure CO{sub 2}, and with co-solvents. > The co-solvent effect of triolein over solubility of {beta}-carotene in CO{sub 2} was higher than ethanol. - Abstract: Modification of an experimental device and methodology improved speed and reproducibility of measurement of solubility of {beta}-carotene in pure and modified SuperCritical (SC) CO{sub 2} at (313 to 333) K. Solubilities of {beta}-carotene in pure CO{sub 2} at (17 to 34) MPa ranged (0.17 to 1.06) {mu}mol/mol and agreed with values reported in literature. The solubility of {beta}-carotene in CO{sub 2} modified with (1.2 to 1.6) % mol ethanol increased by a factor of 1.7 to 3.0 as compared to its solubility in pure CO{sub 2} under equivalent conditions. The concentration of triolein in equilibrated ternary (CO{sub 2} + {beta}-carotene + triolein) mixtures having excess triolein reached values (0.01 to 0.39) mmol/mol corresponding to its solubility in pure SC CO{sub 2} under equivalent conditions. Under these conditions, the solubility of {beta}-carotene in triolein-modified CO{sub 2} increased by a factor of up to 4.0 in relation with its solubility in pure CO{sub 2} at comparable system temperature and pressure, reaching an uppermost value of 3.3 {mu}mol/mol at 333 K and 32 MPa. Unlike in the case of ethanol, where enhancements in solubility where relatively independent on system conditions, solubility enhancements using triolein as co-solvent increased markedly with system pressure, being larger than using (1.2 to 1.6) % mol ethanol at about (24 to 28) MPa, depending on system temperature. The increase in the solubility {beta}-carotene in SC CO{sub 2} as a result of using ethanol or triolein as co-solvent apparently does not depend on the increase in density associated with the dissolution of the co-solvent in CO{sub 2}. Enhancements may be due

Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals.

Science.gov (United States)

Molgaard, Simon; Demontis, Ditte; Nicholson, Alexandra M; Finch, Nicole A; Petersen, Ronald C; Petersen, Claus M; Rademakers, Rosa; Nykjaer, Anders; Glerup, Simon

2016-11-01

Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression and Purification of Soluble STAT5b/STAT3 Proteins for SH2 Domain Binding Assay.

Science.gov (United States)

Asai, Akira; Takakuma, Kazuyuki

2017-01-01

When a large hydrophobic full-length protein is expressed in bacteria, it is often challenging to obtain recombinant proteins in the soluble fraction. One way to overcome this challenge is expression of deletion mutants that have improved solubility while maintaining biological activity. In this chapter, we describe a protocol for expression of truncated forms of STAT5b and STAT3 proteins that are soluble and retain SH2-mediated activity for phospho-Tyr peptide recognition.

Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

Science.gov (United States)

Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

2017-03-01

Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

Interlaboratory validation of small-scale solubility and dissolution measurements of poorly water-soluble drugs

DEFF Research Database (Denmark)

Andersson, Sara B. E.; Alvebratt, Caroline; Bevernage, Jan

2016-01-01

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at m...

Synthesis and evaluation of mesoporous carbon/lipid bilayer nanocomposites for improved oral delivery of the poorly water-soluble drug, nimodipine.

Science.gov (United States)

Zhang, Yanzhuo; Zhao, Qinfu; Zhu, Wufu; Zhang, Lihua; Han, Jin; Lin, Qisi; Ai, Fengwei

2015-07-01

A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core-shell structure was synthesized and characterized as an oral drug delivery system for poorly water-soluble drugs. The objective of this study was to investigate the potential of MCLN-based formulation to modulate the in vitro release and in vivo absorption of a model drug, nimodipine (NIM). NIM-loaded MCLN was prepared by a procedure involving a combination of thin-film hydration and lyophilization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area analysis, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in beagle dogs was compared with that of the immediate-release formulation, Nimotop®. Our results demonstrate that the NIM-loaded MCLN formulation exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation achieved a greater degree of absorption and longer lasting plasma drug levels compared with the commercial formulation. The relative bioavailability of NIM for NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. The data reported herein suggest that the MCLN matrix is a promising carrier for controlling the drug release rate and improving the oral absorption of poorly water-soluble drugs.

Novel furosemide cocrystals and selection of high solubility drug forms.

Science.gov (United States)

Goud, N Rajesh; Gangavaram, Swarupa; Suresh, Kuthuru; Pal, Sharmistha; Manjunatha, Sulur G; Nambiar, Sudhir; Nangia, Ashwini

2012-02-01

Furosemide was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover cocrystals of improved physicochemical properties, that is high solubility and good stability. Eight novel equimolar cocrystals of furosemide were obtained by liquid-assisted grinding with (i) caffeine, (ii) urea, (iii) p-aminobenzoic acid, (iv) acetamide, (v) nicotinamide, (vi) isonicotinamide, (vii) adenine, and (viii) cytosine. The product crystalline phases were characterized by powder x-ray diffraction, differential scanning calorimetry, infrared, Raman, near IR, and (13) C solid-state NMR spectroscopy. Furosemide-caffeine was characterized as a neutral cocrystal and furosemide-cytosine an ionic salt by single crystal x-ray diffraction. The stability of furosemide-caffeine, furosemide-adenine, and furosemide-cytosine was comparable to the reference drug in 10% ethanol-water slurry; there was no evidence of dissociation of the cocrystal to furosemide for up to 48 h. The other five cocrystals transformed to furosemide within 24 h. The solubility order for the stable forms is furosemide-cytosine > furosemide-adenine > furosemide-caffeine, and their solubilities are approximately 11-, 7-, and 6-fold higher than furosemide. The dissolution rates of furosemide cocrystals were about two times faster than the pure drug. Three novel furosemide compounds of higher solubility and good phase stability were identified in a solid form screen. Copyright © 2011 Wiley Periodicals, Inc.

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

Science.gov (United States)

Čerpnjak, Katja; Zvonar, Alenka; Vrečer, Franc; Gašperlin, Mirjana

2015-01-01

Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

Molecular characterization of whey protein hydrolysate fractions with ferrous chelating and enhanced iron solubility capabilities.

Science.gov (United States)

O'Loughlin, Ian B; Kelly, Phil M; Murray, Brian A; FitzGerald, Richard J; Brodkorb, Andre

2015-03-18

The ferrous (Fe2+) chelating capabilities of WPI hydrolysate fractions produced via cascade membrane filtration were investigated, specifically 1 kDa permeate (P) and 30 kDa retentate (R) fractions. The 1 kDa-P possessed a Fe2+ chelating capability at 1 g L(-1) equivalent to 84.4 μM EDTA (for 30 kDa-R the value was 8.7 μM EDTA). Fourier transformed infrared (FTIR) spectroscopy was utilized to investigate the structural characteristics of hydrolysates and molecular interactions with Fe2+. Solid-phase extraction was employed to enrich for chelating activity; the most potent chelating fraction was enriched in histidine and lysine. The solubility of ferrous sulfate solutions (10 mM) over a range of pH values was significantly (Piron solubility was improved by 72% in the presence of the 1 kDa-P fraction following simulated gastrointestinal digestion (SGID) compared to control FeSO4·7H2O solutions.

Solubility limits of importance to leaching

International Nuclear Information System (INIS)

Ogard, A.; Bentley, G.; Bryant, E.; Duffy, C.; Grisham, J.; Norris, E.; Orth, C.; Thomas, K.

1981-01-01

The solubilities of some radionuclides, especially rare earths and actinides, may be an important and controlling factor in leaching of waste forms. These solubilities should be measured accurately as a function of pH and not as a part of a multicomponent system. Individual solubilities should be measured as a function of temperature to determine if a kinetic effect is being observed in the data. A negative temperature coefficient of solubility for actinides and rare earths in water would have important consequences for nuclear reactor safety and for the management of nuclear wastes

Impact of the counterion on the solubility and physicochemical properties of salts of carboxylic acid drugs.

Science.gov (United States)

David, S E; Timmins, P; Conway, B R

2012-01-01

Salt formation is a widely used approach to improve the physicochemical and solid state properties of an active pharmaceutical ingredient. In order to better understand the relationships between the active drug, the selected counterion and the resultant salt form, crystalline salts were formed using four different carboxylic acid drugs and a closely related series of amine counterions. Thirty-six related crystalline salts were prepared, characterized and the relationship between solubility and dissolution behaviour and other properties of the salt and the counterion studied. Salts of four model acid drugs, gemfibrozil, flurbiprofen, ibuprofen and etodolac were prepared using the counterions butylamine, hexylamine, octylamine, benzylamine, cyclohexylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, 2-amino-2-methylpropan-1,3-diol and tris(hydroxymethyl)aminomethane. Salt formation was confirmed, the salts were characterized and their corresponding solubilities determined and rationalized with respect to the counterions' properties. The properties of the salt highly dependent on the nature of the counterion and, although there is considerable variation, some general conclusion can be drawn. For the alkyl amines series, increasing chain length leads to a reduction in solubility across all the acidic drugs studied and a reduction in melting point, thus contradicting simplistic relationships between solubility and melting point. Small, compact counterions consistently produce crystalline salts with high melting point accompanied with a modest improvement in solubility and the nature of hydrogen bonding between the ions has a major impact on the solubility.

Simultaneous Description of Activity Coefficients and Solubility with eCPA

DEFF Research Database (Denmark)

Schlaikjer, Anders; Thomsen, Kaj; Kontogeorgis, Georgios

2017-01-01

with salt specific parameters. The focus is on accurate description of the salt solubility, and low deviation correlations are obtained for all salts investigated. The inclusion of the solubility data in the parametrization has, compared to parameters only parametrized to osmotic coefficients and activity...... coefficients, not significantly affected the deviations of the osmotic coefficients and activity coefficients. The average deviations of the activity coefficient does increase slightly and it was found that the increase in deviations was almost entirely due to reduced accuracy at high temperature and high...... molality. The model is, furthermore, compared to the activity coefficient model, Extended UNIQUAC. It is shown that the eCPA provides more accurate solubility description at higher temperatures than Extended UNIQUAC but also that Extended UNIQUAC is slightly better at describing the activity coefficients...

Solubility and stability of dalcetrapib in vehicles and biological media.

Science.gov (United States)

Gross, Günter; Tardio, Joseph; Kuhlmann, Olaf

2012-11-01

Dalcetrapib solubility was determined in aqueous and in non-aqueous vehicles and in biorelevant media. In a pure aqueous environment the solubility was low but could be increased by addition of surfactants or complexing agents. This was also reflected in the solubility seen in simulated gastrointestinal (GI) fluids, with almost no solubility in simulated gastric fluid, but reasonable solubilisation in simulated intestinal fluids containing lecithin and bile salt. Additionally, the stability of dalcetrapib was determined in simulated GI fluids with and without pancreatic lipase. In solutions without lipase, dalcetrapib was slowly hydrolysed, but in the presence of lipase the hydrolysis rate was significantly faster depending on pH and enzyme activity. In biological fluids, dissolved dalcetrapib appeared to behave similarly being rapidly hydrolysed in human intestinal fluids with a half-life below 20s with no degradation observed in human gastric fluids at low pH. The results provide supportive evidence that absorption is higher under fed conditions and indicate lipase inhibitors might interfere with oral absorption of dalcetrapib. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2015-01-25

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

Profiling and relationship of water-soluble sugar and protein compositions in soybean seeds.

Science.gov (United States)

Yu, Xiaomin; Yuan, Fengjie; Fu, Xujun; Zhu, Danhua

2016-04-01

Sugar and protein are important quality traits in soybean seeds for making soy-based food products. However, the investigations on both compositions and their relationship have rarely been reported. In this study, a total of 35 soybean germplasms collected from Zhejiang province of China, were evaluated for both water-soluble sugar and protein. The total water-soluble sugar (TWSS) content of the germplasms studied ranged from 84.70 to 140.91 mg/g and the water-soluble protein (WSP) content varied from 26.5% to 36.0%. The WSP content showed positive correlations with the TWSS and sucrose contents but negative correlations with the fructose and glucose contents. The clustering showed the 35 germplasms could be divided into four groups with specific contents of sugar and protein. The combination of water-soluble sugar and protein profiles provides useful information for future breeding and genetic research. This investigation will facilitate future work for seed quality improvement. Copyright © 2015. Published by Elsevier Ltd.

Rapid determination of water- and fat-soluble vitamins with microemulsion electrokinetic chromatography.

Science.gov (United States)

Yin, Changna; Cao, Yuhua; Ding, Shaodong; Wang, Yun

2008-06-06

A rapid, reliable and reproducible method based on microemulsion electrokinetic chromatography (MEEKC) for simultaneous determination of 13 kinds of water- and fat-soluble vitamins has been developed in this work. A novel microemulsion system consisting of 1.2% (w/w) sodium lauryl sulphate (SDS), 21% (v/v) 1-butanol, 18% (v/v) acetonitrile, 0.8% (w/w) n-hexane, 20mM borax buffer (pH 8.7) was applied to improve selectivity and efficiency, as well as shorten analysis time. The composition of microemulsion used as the MEEKC running buffer was investigated thoroughly to obtain stable separation medium, as well as the optimum determination conditions. Acetonitrile as the organic solvent modifier, pH of the running buffer and 1-butanol as the co-surfactant played the most important roles for the separation of the fat-soluble vitamins, water-soluble vitamins and stabilization of system, respectively. The 13 water- and fat-soluble vitamins were baseline separated within 30 min. The system was applied to determine water- and fat-soluble vitamins in commercial multivitamin pharmaceutical formulation, good accuracy and precision were obtained with recoveries between 97% and 105%, relative standard derivations (RSDs) less than 1.8% except vitamin C, and acceptable quantitative results corresponding to label claim.

Improvement of the photovoltaic parameters of perovskite solar cells using a reduced-graphene-oxide-modified titania layer and soluble copper phthalocyanine as a hole transporter.

Science.gov (United States)

Nouri, Esmaiel; Mohammadi, Mohammad Reza; Xu, Zong-Xiang; Dracopoulos, Vassilios; Lianos, Panagiotis

2018-01-24

Functional perovskite solar cells can be made by using a simple, inexpensive and stable soluble tetra-n-butyl-substituted copper phthalocyanine (CuBuPc) as a hole transporter. In the present study, TiO 2 /reduced graphene oxide (T/RGO) hybrids were synthesized via an in situ solvothermal process and used as electron acceptor/transport mediators in mesoscopic perovskite solar cells based on soluble CuBuPc as a hole transporter and on graphene oxide (GO) as a buffer layer. The impact of the RGO content on the optoelectronic properties of T/RGO hybrids and on the solar cell performance was studied, suggesting improved electron transport characteristics and photovoltaic parameters. An enhanced electron lifetime and recombination resistance led to an increase in the short circuit current density, open circuit voltage and fill factor. The device based on a T/RGO mesoporous layer with an optimal RGO content of 0.2 wt% showed 22% higher photoconversion efficiency and higher stability compared with pristine TiO 2 -based devices.

Hydrogen solubility and permeability of Nb-W-Mo alloy membrane

International Nuclear Information System (INIS)

Awakura, Y.; Nambu, T.; Matsumoto, Y.; Yukawa, H.

2011-01-01

Research highlights: → The concept for alloy design of Nb-based hydrogen permeable membrane has been applied to Nb-W-Mo ternary alloy in order to improve further the resistance to hydrogen embrittlement and hydrogen permeability. → The alloying effects of Mo on the hydriding properties of Nb-W alloy have been elucidated. → The addition of Mo and/or W into niobium improves the resistance to hydrogen embrittlement by reducing the dissolved hydrogen concentration in the alloy. → Nb-W-Mo alloy possesses excellent hydrogen permeability together with strong resistance to hydrogen embrittlement. - Abstract: The alloying effects of molybdenum on the hydrogen solubility, the resistance to hydrogen embrittlement and the hydrogen permeability are investigated for Nb-W-Mo system. It is found that the hydrogen solubility decreases by the addition of molybdenum into Nb-W alloy. As a result, the resistance to hydrogen embrittlement improves by reducing the hydrogen concentration in the alloy. It is demonstrated that Nb-5 mol%W-5 mol%Mo alloy possesses excellent hydrogen permeability without showing any hydrogen embrittlement when used under appropriate hydrogen permeation conditions, i.e., temperature and hydrogen pressures.

MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

Directory of Open Access Journals (Sweden)

Tu'uhevaha J Kaitu'u-Lino

Full Text Available Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03 up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8 compared to gestationally matched preterm controls (n = 8. However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

Solubility of 1-aminoanthraquinone and 1-nitroanthraquinone in supercritical carbon dioxide

International Nuclear Information System (INIS)

Tamura, Kazuhiro; Alwi, Ratna Surya; Tanaka, Tatsuro; Shimizu, Keisuke

2017-01-01

Highlights: • Solubility of 1-aminoanthraquinone and 1-nitroanthraquinone in scCO 2 were measured. • Temperature ranges of (323.15–383.15) K and pressures of (12.5–25.0) MPa. • Solubility of 1-aminoanthraquinone was higher than that of 1-nitroanthraquinone. • Demonstrated effect of amino and nitro groups on the solubility of anthraquinones. • Correlated well by CO 2 density models and thermodynamic models. - Abstract: The solubility of 1-aminoanthraquinone (Smoke Orange G) and 1-nitroanthraquinone in supercritical carbon dioxide (scCO 2 ) was measured at the temperatures (323.15, 353.15 and 383.15) K and over the pressure range of (12.5–25.0) MPa by a flow type apparatus. Mole fraction solubility of 1-aminoanthraquinone, 3.51 × 10 −5 , was significantly higher than that of 1-nitroanthraquinone, 2.52 × 10 −5 , as compared at 383.15 K and 25 MPa. It was found that amino group in 1-aminoanthraquinone effects to enhance the solubility of anthraquinone derivatives in supercritical carbon dioxide in comparison with nitro group in 1-nitroanthraquinone. Seven different kinds of semi-empirical models, expressed in terms of CO 2 density, were used to correlate the experimental results. Moreover, the solubilities of anthraquinone derivatives were analysed thermodynamically by the regular solution model with the Flory–Huggins theory and by the Peng–Robinson equation of state with a modification of Stryjek and Vera (PRSV-EOS). Good agreement with slightly less than 15 per cent of relative deviation between the experimental and calculated solubilities of the anthraquinone derivatives was obtained.

Prediction of aqueous and nonaqueous solubilities of chemicals with environmental interest by UNIFAC

International Nuclear Information System (INIS)

Kan, A.T.; Tomson, M.B.

1995-01-01

This paper is to investigate the accuracy and precision of predicting the aqueous and non-aqueous solubilities of a vast number of chemicals with significant environmental roles using the latest version of UNIFAC group interaction parameters. A few critical measurements to test specific UNIFAC calculations of nonaqueous solubilities are also reported. The chemicals included in the calculation have aqueous solubilities that span eleven orders of magnitude. Good agreement was observed between the UNIFAC predicted and literature reported aqueous solubilities for eleven groups of compounds. Similarly, UNIFAC successfully predicts the co-solvency of PCB in methanol/water solutions. The error between predicted and literature reported aqueous solubilities was larger for three groups of chemicals: long chain alkanes, phthalates, and chlorinated alkenes. The average absolute error in UNIFAC precision of aqueous solubilities is about 0.5 log units, but the average absolute error is only about 0.2 log units for chlorinated aromatic compounds in organic solvents. The application of UNIFAC approach to predict the fate of hydrocarbons and PCBs in soil column flushing, cosolvency and in natural gas pipeline liquids will be discussed

Uranyl Oxalate Solubility

Energy Technology Data Exchange (ETDEWEB)

Leturcq, G.; Costenoble, S.; Grandjean, S. [CEA Marcoule DEN/DRCP/SCPS/LCA - BP17171 - 30207 Bagnols sur Ceze cedex (France)

2008-07-01

The solubility of uranyl oxalate was determined at ambient temperature by precipitation in oxalic-nitric solutions, using an initial uranyl concentration of 0.1 mol/L. Oxalic concentration varied from 0.075 to 0.3 mol/L while nitric concentration ranged between 0.75 and 3 mol/L. Dissolution tests, using complementary oxalic-nitric media, were carried out for 550 hours in order to study the kinetic to reach thermodynamic equilibrium. Similar solubility values were reached by dissolution and precipitation. Using the results, it was possible to draw the solubility surface versus oxalic and nitric concentrations and to determine both the apparent solubility constant of UO{sub 2}C{sub 2}O{sub 4}, 3H{sub 2}O (Ks) and the apparent formation constant of the first uranyl-oxalate complex UO{sub 2}C{sub 2}O{sub 4} (log {beta}1), for ionic strengths varying between 1 and 3 mol/L. Ks and log {beta}1 values were found to vary from 1.9 10{sup -8} to 9.2 10{sup -9} and from 5.95 to 6.06, respectively, when ionic strength varied from 1 to 3 mol/L. A second model may fit our data obtained at an ionic strength of 3 mol/L suggesting as reported by Moskvin et al. (1959) that no complexes are formed for [H{sup +}] at 3 M. The Ks value would then be 1.3 10{sup -8}. (authors)

Solubility and fluoride release in ionomers and compomers.

Science.gov (United States)

Bertacchini, S M; Abate, P F; Blank, A; Baglieto, M F; Macchi, R L

1999-03-01

The degree of solubility and the fluoride release of glass-ionomer cements and "compomers" were determined as a function of time. Three conventional glass-ionomer cements, three hybrid ionomers, and two compomers were included in the study. Disk-shaped specimens were prepared and immersed in a lactic acid solution. Solubility was evaluated from determinations of loss of mass as a function of time. To evaluate fluoride release, similar specimens were immersed in 50 mL of deionized water to which 50 mL of buffer solution was added. A fluoride ion detector was used to read the concentration of fluoride ion in the overall solution at different times after immersion. Material and time factors had a significant influence on results. The compomers showed less corrosion and fluoride release than the ionomers. Some correlation was found between solubility and fluoride leakage values. Components of both the ionomers and compomers that were studied can dissolve in water. The materials leak fluoride ions in amounts that differ according to the characteristics of the individual products.

Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury

International Nuclear Information System (INIS)

Yin Hui; Huang Baojun; Yang Heng; Huang Yafei; Xiong Ping; Zheng Fang; Chen Xiaoping; Chen Yifa; Gong Feili

2006-01-01

The interleukin-1 receptor-like protein ST2 exists in both membrane-bound (ST2L) and soluble form (sST2). ST2L has been found to play an important regulatory role in Th2-type immune response, but the function of soluble form of ST2 remains to be elucidated. In this study, we report the protective effect of soluble ST2 on warm hepatic ischemia/reperfusion injury. We constructed a eukaryotic expression plasmid, psST2-Fc, which expresses functional murine soluble ST2-human IgG1 Fc (sST2-Fc) fusion protein. The liver damage after ischemia/reperfusion was significantly attenuated by the expression of this plasmid in vivo. sST2-Fc remarkably inhibited the activation of Kupffer cells and the production of proinflammatory mediators TNF-α and IL-6. Furthermore, the levels of TLR4 mRNA and the nuclear translocation of NF-κB were also suppressed by pretreatment with sST2-Fc. These results thus identified soluble ST2 as a negative regulator in hepatic I/R injury, possibly via ST2-TLR4 pathway

Solubility behavior of narcotic analgesics in aqueous media: solubilities and dissociation constants of morphine, fentanyl, and sufentanil.

Science.gov (United States)

Roy, S D; Flynn, G L

1989-02-01

The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35 degrees C. Dissociation constants and corresponding pKa' values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa' values of 8.08, 8.99, and 8.51, respectively. Over the pH range of 5 to 12.5 the apparent solubilities are determined by the intrinsic solubility of the free base plus the concentration of ionized drug necessary to satisfy the dissociation equilibrium at a given pH. Consequently, the drug concentrations of saturated aqueous solutions fall off precipitously as the pH is raised and ionization is suppressed. Further, at low pH's the aqueous solubility of morphine increased in a linear fashion with increases in the molar strength of citric acid which was added to acidify the medium, suggesting the formation of a soluble morphine-citrate complex.

Solubility studies of Np(IV)

International Nuclear Information System (INIS)

Zhang Yingjie; Yao Jun; Jiao Haiyang; Ren Lihong; Zhou Duo; Fan Xianhua

2001-01-01

The solubility of Np(IV) in simulated underground water and redistilled water has been measured with the variations of pH(6-12) and storage time (0-100 d) in the presence of reductant (Na 2 S 2 O 4 , metallic Fe). All experiments are performed in a low oxygen concentration glove box containing high purity Ar(99.99%), with an oxygen content of less than 5 x 10 -6 mol/mol. Experimental results show that the variation of pH in solution has little effect on the solubility of Np(IV) in the two kinds of water; the measured solubility of Np(IV) is affected by the composition of solution; with Na 2 S 2 O 4 as a reductant, the solubility of Np(IV) in simulated underground water is (9.23 +- 0.48) x 10 -10 mol/L, and that in redistilled water is (8.31 +- 0.35) x 10 -10 mol/L; with metallic Fe as a reductant, the solubility of Np(IV) in simulated underground water is (1.85 +- 0.56) x 10 -9 mol/L, and that in redistilled water is (1.48 +- 0.66) x 10 -9 mol/L

Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management.

Science.gov (United States)

Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio; Crespo, Juan J; Ríos, María T; Smolensky, Michael H

2017-10-01

Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of 6 different classes and their combinations significantly improves BP control, particularly sleep-time BP, and reduces adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Solubility of Nd in brine

International Nuclear Information System (INIS)

Khalili, F.I.; Symeopoulos, V.; Chen, J.F.; Choppin, G.R.

1994-01-01

The solubility of Nd(III) has been measured at 23±3 C in a synthetic brine at pcH 6.4, 8.4, 10.4 and 12.4. The brine consisted predominantly of (Na+K)Cl and MgCl 2 with an ionic strength of 7.8 M (9.4 m) a solid compound of Nd(III) at each pcH was assigned from X-ray diffraction patterns. The log values of the experimental solubilities decrease fomr -3 at pcH 6.4 to -5.8 at pcH 8.4; at pcH 10.4 and 12.4 the solubility was below the detection limit of -7.5. The experimental solubility does not follow closely the variation with pcH estimated from modeling of the species in solution in equilibrium with the Nd solid using S.I.T. (orig.)

National Emergency Preparedness and Response: Improving for Incidents of National Significance

National Research Council Canada - National Science Library

Clayton, Christopher M

2006-01-01

The national emergency management system has need of significant improvement in its contingency planning and early consolidation of effort and coordination between federal, state, and local agencies...

Effect of biosurfactants on the aqueous solubility of PCE and TCE.

Science.gov (United States)

Albino, John D; Nambi, Indumathi M

2009-12-01

The effect of biosurfactants on the solubility of tetrachloroethylene (PCE) and trichloroethylene (TCE) was studied in batch experiments pertaining to their use for solubilization and mobilization of such contaminants in surfactant enhanced aquifer remediation. Biosurfactants, rhamnolipid and surfactin used in solubility studies were synthesized in our laboratory by Pseudomonas aeruginosa (MTCC 2297) and Bacillus subtilis (MTCC 2423), respectively. The efficiency of the biosurfactants in solubilizing the chlorinated solvents was compared to that of synthetic surfactants. The Weight Solubilization Ratio (WSR) values for solubilization of PCE and TCE by biosurfactants were very high compared to the values obtained for synthetic surfactants. Surfactin proved to be a better surfactant over rhamnolipid. The WSR of surfactin on solubilization of PCE and TCE were 3.83 and 12.5, respectively, whereas the values obtained for rhamnolipid were 2.06 and 8.36. The solubility of the chlorinated solvents by biosurfactants was considerably affected by the changes in pH. The aqueous solubility of PCE and TCE increased tremendously with decrease in pH. The solubility of biosurfactants was observed to decrease with the pH, favoring partitioning of surfactants into the chlorinated solvents in significant amounts at lower pH. The excessive accumulation of biosurfactants at the interface facilitated interfacial tension reductions resulting in higher solubility of the chlorinated solvents at pH less than 7.

Nanotechnology Based Approaches for Enhancing Oral Bioavailability of Poorly Water Soluble Antihypertensive Drugs

Directory of Open Access Journals (Sweden)

Mayank Sharma

2016-01-01

Full Text Available Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.

Solubility of magnetite in coolant of NPP boiling reactor

International Nuclear Information System (INIS)

Zarembo, V.I.; Kritskij, V.G.; Slobodov, A.A.; Puchkov, L.V.

1988-01-01

To improve water-chemical NPP regimes calculations of iron solubility up to 600 K temperature in Fe 3 O 4 -H 2 O-O 2 and Fe(OH) 3 -H 2 O systems are performed using a system of selected and consistent values of thermal constants of various chemical iron forms in standard aqueous solution state. Calculations have shown that up to 423 K in aqueous medium containing oxygen, magnetite is unstable and is oxidized first up to Fe(OH) 3 and then - up to Fe OOH and Fe 2 O 3 . Calculations complying with experimental data have demonstrated the presence of maximum on the curve solubility-temperature in desalinized water containing 10 μkg/kg of oxygen. A sequence of processes of oxygen effect on water regime and corrosion prduct deposition in a condensate-feed circuit of NPP boiling reactor is proposed. It is proved that under oxygen water chemistry of condensate-feed circuit after magnetite transfomation into gematite, reduction of soluble iron form inlet to reactor loop occurs, which allows one to expect reduction of γ-radiation dose rate buildup around the primary loop pipelines

Importance of critical micellar concentration for the prediction of solubility enhancement in biorelevant media.

Science.gov (United States)

Ottaviani, G; Wendelspiess, S; Alvarez-Sánchez, R

2015-04-06

This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF). The solubility of 51 chemically diverse compounds was measured in FaSSIF and in phosphate buffer and the surface activity parameters were determined. This study showed that the compound critical micellar concentration parameter (CMC) correlates strongly with the solubility enhancement (SE) observed in FaSSIF compared to phosphate buffer. Thus, the intrinsic capacity of molecules to form micelles is also a determinant for each compound's affinity to the micelles of biorelevant surfactants. CMC correlated better with SE than lipophilicity (logD), especially over the logD range typically covered by drugs (2 < logD < 4). CMC can become useful to guide drug discovery scientists to better diagnose, improve, and predict solubility in biorelevant media, thereby enhancing oral bioavailability of drug candidates.

Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods.

Science.gov (United States)

Boaz, Segal M; Champagne, Cory D; Fowler, Melinda A; Houser, Dorian H; Crocker, Daniel E

2012-02-01

Despite the importance of water-soluble vitamins to metabolism, there is limited knowledge of their serum availability in fasting wildlife. We evaluated changes in water-soluble vitamins in northern elephant seals, a species with an exceptional ability to withstand nutrient deprivation. We used a metabolomics approach to measure vitamins and associated metabolites under extended natural fasts for up to 7 weeks in free-ranging lactating or developing seals. Water-soluble vitamins were not detected with this metabolomics platform, but could be measured with standard assays. Concentrations of measured vitamins varied independently, but all were maintained at detectable levels over extended fasts, suggesting that defense of vitamin levels is a component of fasting adaptation in the seals. Metabolomics was not ideal for generating complete vitamin profiles in this species, but gave novel insights into vitamin metabolism by detecting key related metabolites. For example, niacin level reductions in lactating females were associated with significant reductions in precursors suggesting downregulation of the niacin synthetic pathway. The ability to detect individual vitamins using metabolomics may be impacted by the large number of novel compounds detected. Modifications to the analysis platforms and compound detection algorithms used in this study may be required for improving water-soluble vitamin detection in this and other novel wildlife systems. Copyright © 2011 Elsevier Inc. All rights reserved.

OZONE TREATMENT OF SOLUBLE ORGANICS IN PRODUCED WATER

Energy Technology Data Exchange (ETDEWEB)

Klasson, KT

2002-03-14

This project was an extension of previous research to improve the applicability of ozonation and will help address the petroleum-industry problem of treating produced water containing soluble organics. The goal of this project was to maximize oxidation of hexane-extractable organics during a single-pass operation. The project investigated: (1) oxidant production by electrochemical and sonochemical methods, (2) increasing the mass transfer rate in the reactor by forming microbubbles during ozone injection into the produced water, and (3) using ultraviolet irradiation to enhance the reaction if needed. Several types of methodologies for treatment of soluble organics in synthetic and actual produced waters have been performed. The technologies tested may be categorized as follows: (1) Destruction via sonochemical oxidation at different pH, salt concentration, ultraviolet irradiation, and ferrous iron concentrations. (2) Destruction via ozonation at different pH, salt concentration, hydrogen peroxide concentrations, ultraviolet irradiation, temperature, and reactor configurations.

Gallic acid/hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms.

Directory of Open Access Journals (Sweden)

Guilherme Rodrigues Teodoro

Full Text Available The aim of this study was to increase the solubility of gallic acid (GA for the treatment of Candida albicans biofilm, which is very difficult to treat and requires high drug concentrations. Cyclodextrins (CDs were used for this purpose. Complexes were evaluated by phase-solubility studies, prepared by spray drying and characterized by drug loading, scanning electron microscopy (SEM and differential scanning calorimetry (DSC. The complexes were tested on C. albicans biofilm using in vitro and in vivo models. HPβCD formed soluble inclusion complexes with GA. The percentage of GA in GA/HPβCD was 10.8 ± 0.01%. The SEM and DSC analyses confirmed the formation of inclusion complexes. GA/HPβCD maintained the antimicrobial activity of the pure GA. GA/HPβCD was effective on C. albicans biofilms of 24 and 48h. The in vivo results showed an anti-inflammatory activity of GA/HPβCD with no difference in invading hypha counting among the groups. This study encourages the development of new antifungal agents.

Solubility database for TILA-99

Energy Technology Data Exchange (ETDEWEB)

Vuorinen, U.; Carlsson, T. [VTT Chemical Technology, Espoo (Finland); Kulmala, S.; Hakanen, M. [Helsinki Univ. (Finland). Lab. of Radiochemistry; Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

1998-11-01

The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water ({approx}70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites

Solubility database for TILA-99

International Nuclear Information System (INIS)

Vuorinen, U.; Carlsson, T.; Kulmala, S.; Hakanen, M.

1998-11-01

The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water (∼70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites. The

Recent Progress in the Development of Supercritical Carbon Dioxide-Soluble Metal Ion Extractants: Aggregation, Extraction, and Solubility Properties of Silicon-Substituted Alkylenediphosphonic Acids

Energy Technology Data Exchange (ETDEWEB)

Dietz, Mark L.; McAlister, Daniel R.; Stepinski, Dominique C.; Zalupski, Peter R.; Dzilawa, Julie A.; Barrans, Richard E.; Hess, J.N.; Rubas, Audris V.; Chiarizia, Renato; Lubbers, Christopher M.; Scurto, Aaron M.; Brennecke, Joan F.; Herlinger, Albert W.

2003-09-11

Partially esterified alkylenediphosphonic acids (DPAs) have been shown to be effective reagents for the extraction of actinide ions from acidic aqueous solution into conventional organic solvents. Efforts to employ these compounds in supercritical fluid extraction have been hampered by their modest solubility in unmodified supercritical carbon dioxide (SC-CO2). In an effort to design DPAs that are soluble in SC-CO2, a variety of silicon-substituted alkylenediphosphonic acids have been prepared and characterized, and their behavior compared with that of conventional alkyl-substituted reagents. Silicon substitution is shown to enhance the CO2-philicity of the reagents, while other structural features, in particular, the number of methylene groups bridging the phosphorus atoms of the extractant, are shown to exert a significant influence on their aggregation and extraction properties. The identification of DPAs combining desirable extraction properties with adequate solubility in SC-CO2 is shown to be facilitated by the application of molecular connectivity indices.

Application of spray-drying and electrospraying/electospinning for poorly water-soluble drugs

DEFF Research Database (Denmark)

Bohr, Adam; Boetker, Johan P; Rades, Thomas

2014-01-01

Solid dispersions have been widely studied as an attractive formulation strategy for the increasingly prevalent poorly water-soluble drug compounds, including herbal medicines, often leading to improvements in drug dissolution rate and bioavailability. However, several challenges are encountered...

Effect of X-irradiation on soluble nucleohistone of Pinus pinea

International Nuclear Information System (INIS)

Berkofsky, J.; Roy, R.M.

1977-01-01

Exposure of isolated nuclei from Pinus pinea cotyledons to 5 kR of 260 kVp X-rays resulted in no significant alteration of viscosity, thermal denaturation or spectral characteristics of soluble nucleohistone nor was the relative amount of DNA, RNA, histone and acidic protein affected. Pine histones, resolved into 8 sub-fractions by polyacrylamide gel electrophoresis, appeared to be unaffected with respect to mobility or relative abundance following irradiation of cotyledons, isolated nuclei, soluble nucleohistone or histones. However, phosphorylation of histones at AT 32 P following irradiation of isolated nuclei with 5 kR was significantly inhibited. Although histone F 1 phosphorylation was inhibited to the greatest extent as previously reported for mammalian tissues, significant inhibition of phosphorylation of histone F 2 a2 and F 2 b was observed. Exposure of cotyledons at the 14th day of germination to 1.0 kR resulted in an apparent G 2 mitotic block within 1 hr post irradiation. The normal increase in histone content of soluble nucleohistone associated with the termination of cell division and onset of cell elongation in the cotyledon at this time was inhibited. Mitotic activity remained arrested for approximately 2 days. Recovery of mitotic activity in the irradiated cotyledons was correlated with resumption of deposition of histone into chromatin preceding the onset of cell elongation. (author)

Coformer selection in pharmaceutical cocrystal development: a case study of a meloxicam aspirin cocrystal that exhibits enhanced solubility and pharmacokinetics.

Science.gov (United States)

Cheney, Miranda L; Weyna, David R; Shan, Ning; Hanna, Mazen; Wojtas, Lukasz; Zaworotko, Michael J

2011-06-01

Meloxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility and high permeability. Because of its low solubility under acidic conditions (e.g., pH 1-5), it can take more than 2 h for meloxicam to reach its therapeutic concentration in humans. Although the slow onset of meloxicam does not necessarily impact the current label indications, the slow onset does prevent meloxicam from its potential application for the relief of mild-to-medium-level acute pain. Pharmaceutical cocrystallization of meloxicam, which represents a promising approach to generate diverse novel crystal forms, could be used to improve the aqueous solubility and accelerate the onset of action. In this contribution, we describe how a novel method can be used for coformer selection to enable the efficient and effective development of a pharmaceutical cocrystal with desired physicochemical and pharmacokinetic properties. Aspirin was selected as the coformer for meloxicam based upon this alternative route, which combines the supramolecular synthon approach with findings in the previous pharmacological and toxicological studies of meloxicam. The resulting cocrystal of meloxicam and aspirin exhibited superior kinetic solubility and possessed the potential to significantly decrease the time required to reach the human therapeutic concentration compared with the parent drug, meloxicam. Copyright © 2010 Wiley-Liss, Inc.

A Fluid Membrane-Based Soluble Ligand Display System for Live CellAssays

Energy Technology Data Exchange (ETDEWEB)

Nam, Jwa-Min; Nair, Pradeep N.; Neve, Richard M.; Gray, Joe W.; Groves, Jay T.

2005-10-14

Cell communication modulates numerous biological processes including proliferation, apoptosis, motility, invasion and differentiation. Correspondingly, there has been significant interest in the development of surface display strategies for the presentation of signaling molecules to living cells. This effort has primarily focused on naturally surface-bound ligands, such as extracellular matrix components and cell membranes. Soluble ligands (e.g. growth factors and cytokines) play an important role in intercellular communications, and their display in a surface-bound format would be of great utility in the design of array-based live cell assays. Recently, several cell microarray systems that display cDNA, RNAi, or small molecules in a surface array format were proven to be useful in accelerating high-throughput functional genetic studies and screening therapeutic agents. These surface display methods provide a flexible platform for the systematic, combinatorial investigation of genes and small molecules affecting cellular processes and phenotypes of interest. In an analogous sense, it would be an important advance if one could display soluble signaling ligands in a surface assay format that allows for systematic, patterned presentation of soluble ligands to live cells. Such a technique would make it possible to examine cellular phenotypes of interest in a parallel format with soluble signaling ligands as one of the display parameters. Herein we report a ligand-modified fluid supported lipid bilayer (SLB) assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined. The method reported herein benefits from the naturally fluid state of the supported membrane, which allows

A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

Science.gov (United States)

Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

2017-04-01

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

The Comparison of Sorption and Solubility Behavior of Four Different Resin Luting Cements in Different Storage Media.

Science.gov (United States)

Giti, Rashin; Vojdani, Mahroo; Abduo, Jaafar; Bagheri, Rafat

2016-06-01

Structural integrity and dimensional stability are the key factors that determine the clinical success and durability of luting cements in the oral cavity. Sorption and solubility of self-adhesive resin luting cements in food-simulating solutions has not been studied sufficiently. This study aimed to compare the sorption and solubility of 2 conventional and 2 self-adhesive resin-based luting cements immersed in four different storage media. A total of 32 disc-shaped specimens were prepared from each of four resin luting cements; seT (SDI), Panavia F (Kuraray), Clearfil SA Cement (Kuraray), and Choice 2 (Bisco). Eight specimens of each material were immersed in all tested solutions including n-heptane 97%, distilled water, apple juice, or Listerine mouth wash. Sorption and solubility were measured by weighing the specimens before and after immersion and desiccation. Data were analyzed by SPSS version 18, using two-way ANOVA and Tukey's HSD test with p≤ 0.05 set as the level of significance. There was a statistically significant interaction between the materials and solutions. The effect of media on the sorption and solubility was material-dependent. While seT showed the highest values of the sorption in almost all solutions, Choice 2 showed the least values of sorption and solubility. Immersion in apple juice caused more sorption than other solutions (p≤ 0.05). The sorption and solubility behavior of the studied cements were significantly affected by their composition and the storage media. The more hydrophobic materials with higher filler content like Choice 2 resin cement showed the least sorption and solubility. Due to their lower sorption and solubility, these types of resin-based luting cements are recommended to be used clinically.

Noble gases solubility in water

International Nuclear Information System (INIS)

Crovetto, Rosa; Fernandez Prini, Roberto.

1980-07-01

The available experimental data of solubility of noble gases in water for temperatures smaller than 330 0 C have been critically surveyed. Due to the unique structure of the solvent, the solubility of noble gases in water decreases with temperature passing through a temperature of minimum solubility which is different for each gas, and then increases at higher temperatures. As aresult of the analysis of the experimental data and of the features of the solute-solvent interaction, a generalized equation is proposed which enables thecalculation of Henry's coefficient at different temperatures for all noble gases. (author) [es

Novel association of soluble intercellular adhesion molecule 1 and soluble P-selectin with the ABO blood group in a Chinese population.

Science.gov (United States)

Zhang, Wenjing; Xu, Qun; Zhuang, Yunlong; Chen, Yuanfeng

2016-08-01

Recent studies have reported that the ABO gene can affect circulating expression levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble P-selectin (sP-selectin) in Caucasians. However, several factors may affect the association, including the distribution and variations of the ABO gene, ethnic diversity and the inflammatory response status. The aim of the present study was to investigate this issue in Asian subjects of various blood groups. A total of 800 blood samples were randomly selected from healthy blood donors. The ABO blood groups were examined using standard serological tests, and ABO genotypes of group A and group AB specimens were analyzed. Plasma concentrations of sICAM-1 and sP-selectin were detected by standard enzyme-linked immunosorbent assays. In healthy Chinese individuals, blood group A was detected to be significantly associated with lower circulating expression levels of sICAM-1 and sP-selectin, compared with group O. Individuals with ≥1 A1 allele had significantly lower expression levels of sICAM-1 and sP-selectin compared with all other ABO groups. The data indicate the significant association of ABO blood group antigens with sICAM-1 and sP-selectin expression levels in a healthy Chinese population, independent of the specific variations and distributions of ABO blood groups among ethnic populations. This result provides evidence for the previously unidentified role of ABO blood group antigens in the regulation of the inflammatory adhesion process. Accordingly, it can be proposed that ABO blood groups may require consideration when soluble adhesion molecules are identified as predictors for cardiovascular disease.

Solubility of xenon in amino-acid solutions. II. Nine less-soluble amino acids

Science.gov (United States)

Kennan, Richard P.; Himm, Jeffrey F.; Pollack, Gerald L.

1988-05-01

Ostwald solubility (L) of xenon gas, as the radioisotope 133Xe, has been measured as a function of solute concentration, at 25.0 °C, in aqueous solutions of nine amino acids. The amino-acid concentrations investigated covered much of their solubility ranges in water, viz., asparagine monohydrate (0-0.19 M), cysteine (0-1.16 M), glutamine (0-0.22 M), histidine (0-0.26 M), isoleucine (0-0.19 M), methionine (0-0.22 M), serine (0-0.38 M), threonine (0-1.4 M), and valine (0-0.34 M). We have previously reported solubility results for aqueous solutions of six other, generally more soluble, amino acids (alanine, arginine, glycine, hydroxyproline, lysine, and proline), of sucrose and sodium chloride. In general, L decreases approximately linearly with increasing solute concentration in these solutions. If we postulate that the observed decreases in gas solubility are due to hydration, the results under some assumptions can be used to calculate hydration numbers (H), i.e., the number of H2O molecules associated with each amino-acid solute molecule. The average values of hydration number (H¯) obtained at 25.0 °C are 15.3±1.5 for asparagine, 6.8±0.3 for cysteine, 11.5±1.1 for glutamine, 7.3±0.7 for histidine, 5.9±0.4 for isoleucine, 10.6±0.8 for methionine, 11.2±1.3 for serine, 7.7± 1.0 for threonine, and 6.6±0.6 for valine. We have also measured the temperature dependence of solubility L(T) from 5-40 °C for arginine, glycine, and proline, and obtained hydration numbers H¯(T) in this range. Between 25-40 °C, arginine has an H¯ near zero. This may be evidence for an attractive interaction between xenon and arginine molecules in aqueous solution.

Water insoluble and soluble lipids for gene delivery.

Science.gov (United States)

Mahato, Ram I

2005-04-05

Among various synthetic gene carriers currently in use, liposomes composed of cationic lipids and co-lipids remain the most efficient transfection reagents. Physicochemical properties of lipid/plasmid complexes, such as cationic lipid structure, cationic lipid to co-lipid ratio, charge ratio, particle size and zeta potential have significant influence on gene expression and biodistribution. However, most cationic lipids are toxic and cationic liposomes/plasmid complexes do not disperse well inside the target tissues because of their large particle size. To overcome the problems associated with cationic lipids, we designed water soluble lipopolymers for gene delivery to various cells and tissues. This review provides a critical discussion on how the components of water insoluble and soluble lipids affect their transfection efficiency and biodistribution of lipid/plasmid complexes.

Temperature and curing time affect composite sorption and solubility

Directory of Open Access Journals (Sweden)

Fabrício Luscino Alves de Castro

2013-04-01

Full Text Available Objective: This study evaluated the effect of temperature and curing time on composite sorption and solubility. Material and Methods: Seventy five specimens (8×2 mm were prepared using a commercial composite resin (ICE, SDI. Three temperatures (10°C, 25°C and 60°C and five curing times (5 s, 10 s, 20 s, 40 s and 60 s were evaluated. The specimens were weighed on an analytical balance three times: A: before storage (M1; B: 7 days after storage (M2; C: 7 days after storage plus 1 day of drying (M3. The storage solution consisted of 75% alcohol/25% water. Sorption and solubility were calculated using these three weights and specimen dimensions. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U Tests (α=5%. Results: The results showed that time, temperature and their interaction influenced the sorption and solubility of the composite (p0.05. The 60°C composite temperature led to lower values of sorption for all curing times when compared with the 10°C temperature (p0.05. Solubility was similar at 40 s and 60 s for all temperatures (p>0.05, but was higher at 10°C than at 60°C for all curing times (p0.05. Conclusions: In conclusion, higher temperatures or longer curing times led to lower sorption and solubility values for the composite tested; however, this trend was only significant in specific combinations of temperature and curing times.

Cocrystal solubility-pH and drug solubilization capacity of sodium dodecyl sulfate – mass action model for data analysis and simulation to improve design of experiments

Directory of Open Access Journals (Sweden)

Alex Avdeef

2018-06-01

Full Text Available This review discusses the disposition of the anionic surfactant, sodium dodecyl sulfate (SDS; i.e., sodium lauryl sulfate, to solubilize sparingly-soluble drugs above the surfactant critical micelle concentration (CMC, as quantitated by the solubilization capacity (k. A compilation of 101 published SDS k values of mostly poorly-soluble drug molecules was used to develop a prediction model as a function of the drug’s intrinsic solubility, S0, and its calculated H-bond acceptor/donor potential. In almost all cases, the surfactant was found to solubilize the neutral form of the drug. Using the mass action model, the k values were converted to drug-micelle stoichiometric binding constants, Kn, corresponding to drug-micelle equilibria in drug-saturated solutions. An in-depth case study (data from published sources considered the micellization reactions as a function of pH of a weak base, B, (pKa 3.58, S0 52 μg/mL, where at pH 1 the BH.SDS salt was predicted to precipitate both below and above the CMC. At low SDS concentrations, two drug salts were predicted to co-precipitate: BH.Cl and BH.SDS. Solubility products of both were determined from the analysis of the reported solubility-surfactant data. Above the CMC, in a rare example, the charged form of the drug (BH+ appeared to be strongly solubilized by the surfactant. The constant for that reaction was also determined. At pH 7, the reactions were simpler, as only the neutral form of the drug was solubilized, to a significantly lesser extent than at pH 1. Case studies also featured examples of solubilization of solids in the form of cocrystals. For many cocrystal systems studied in aqueous solution, the anticipated supersaturated state is not long-lasting, as the drug component precipitates to a thermodynamically stable form, thus lowering the amount of the active ingredient available for intestinal absorption. Use of surfactant can prevent this. A recently-described method for predicting the

Sodium tetraphenylborate solubility and dissolution rates

International Nuclear Information System (INIS)

Barnes, M.J.; Peterson, R.A.; Swingle, R.F.; Reeves, C.T.

1995-01-01

The rate of solid sodium tetraphenylborate (NaTPB) dissolution in In-Tank Precipitation salt solutions has been experimentally determined. The data indicates that the dissolution rate of solid NaTPB is a minor contributor the lag time experienced in the 1983 Salt Decontamination Demonstration Test and should not be considered as the rate determining step. Current analytical models for predicting the time to reach the composite lower flammability limit assume that the lag time is not more than 6 hours, and the data supports this assumption (i.e., dissolution by itself requires much less than 6 hours). The data suggests that another step--such as mass transport, the reaction of a benzene precursor or the mixing behavior--is the rate determining factor for benzene release to the vapor space in Tank 48H. In addition, preliminary results from this program show that the degree of agitation employed is not a significant parameter in determining the rate of NaTPB dissolution. As a result of this study, an improved equation for predicting equilibrium tetraphenylborate solubility with respect to temperature and sodium ion concentration has been determined

Reliability of soluble IL-2 receptor measurements obtained with enzyme-linked immunosorbent assay

International Nuclear Information System (INIS)

Akiyama, Mitoshi; Takaishi, Masatoshi; Murakami, Yoshie; Ueda, Ryuzo; Yamakido, Michio; Tsubokura, Tokuo.

1989-09-01

Using an enzyme-linked immunosorbent assay (ELISA), human soluble interleukin-2 receptors (IL-2R) were measured in the serum of patients with various autoimmune system diseases. To study the sensitivity and specificity of the assay, soluble IL-2Rs were measured in the culture supernatants and in the cell extracts of peripheral blood mononuclear cells activated with phytohemagglutinin (PHA), purified protein derivative of tuberculin, and allogeneic lymphocytes, as well as in the serum of patients with various collagen diseases. The results correlated well with reports from other laboratories. For example, when stimulated by PHA, the greatest amount of soluble IL-2Rs was produced at the fastest rate. In addition, soluble IL-2R levels in the serum of collagen disease patients were significantly higher than those in healthy persons, who themselves exhibited low levels of detectable soluble IL-2Rs. It is hoped that reliable ELISA measurements of soluble IL-2Rs in the serum of atomic bomb survivors will assist in the interpretation of data collected during the work described in RP 2-87, a study of autoimmunity and autoimmune diseases in the Adult Health Study. (author)

Determination of soluble protein contents from RVNRL

International Nuclear Information System (INIS)

Wan Manshol Wan Zin; Nurulhuda Othman

1996-01-01

This project was carried out to determine the soluble protein contents on RVNRL film vulcanisates, with respect to the RVNRL storage time, gamma irradiation dose absorbed by the latex and the effect of different leaching time and leaching conditions. These three factors are important in the hope to determine the best possible mean of minimizing the soluble protein contents in products made from RVNRL. Within the nine months storage period employed in the study, the results show that, the longer the storage period the less the soluble protein extracted from the film samples. Gamma irradiation dose absorbed by the samples, between 5.3 kGy to 25.2 kGy seems to influence the soluble protein contents of the RVNRL films vulcanisates. The higher the dose the more was the soluble protein extracted from the film samples. At an absorbed dose of 5.3 kGy and 25.2 kGy, the soluble contents were 0. 198 mg/ml and 0.247 mg/ml respectively. At a fixed leaching temperature, the soluble proteins increases with leaching time and at a fixed leaching time, the soluble proteins increases with leaching temperature. ne highest extractable protein contents was determined at a leaching time of 10 minutes and leaching temperature of 90'C The protein analysis were done by using Modified Lowry Method

Solubility of Tc(IV) oxides

International Nuclear Information System (INIS)

Liu, D.J.; Fan, X.H.

2005-01-01

Full text of publication follows: The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 .nH 2 O. The solubility of Tc(IV) is used as a source term in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2+ . The solubility of Tc(IV) oxide has been determined in simulated groundwater and re-distilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and re-distilled water is about (1.49∼1.86) x 10 -9 mol/(L.d) under aerobic conditions, but Tc(IV) in simulated groundwater and re-distilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and re-distilled water is equal on the whole after centrifugation or ultrafiltration. The solubility of Tc(IV) oxide decreases with the increase of pH at pH 10 and is pH independent in the range 2 -8 to 10 -9 mol/L at 2 3 2- concentration. These data could be used to estimate the Tc(IV) solubility for cases where solubility limits transport of technetium in reducing environments of high-level waste repositories. (authors)

Predicting Soluble Nickel in Soils Using Soil Properties and Total Nickel.

Science.gov (United States)

Zhang, Xiaoqing; Li, Jumei; Wei, Dongpu; Li, Bo; Ma, Yibing

2015-01-01

Soil soluble nickel (Ni) concentration is very important for determining soil Ni toxicity. In the present study, the relationships between soil properties, total and soluble Ni concentrations in soils were developed in a wide range of soils with different properties and climate characteristics. The multiple regressions showed that soil pH and total soil Ni concentrations were the most significant parameters in predicting soluble Ni concentrations with the adjusted determination coefficients (Radj2) values of 0.75 and 0.68 for soils spiked with soluble Ni salt and the spiked soils leached with artificial rainwater to mimic field conditions, respectively. However, when the soils were divided into three categories (pH 8), they obtained better predictions with Radj2 values of 0.78-0.90 and 0.79-0.94 for leached and unleached soils, respectively. Meanwhile, the other soil properties, such as amorphous Fe and Al oxides and clay, were also found to be important for determining soluble Ni concentrations, indicating that they were also presented as active adsorbent surfaces. Additionally, the whole soil speciation including bulk soil properties and total soils Ni concentrations were analyzed by mechanistic speciation models WHAM VI and Visual MINTEQ3.0. It was found that WHAM VI provided the best predictions for the soils with pH 8. The Visual MINTEQ3.0 could provide better estimation for pH 8. These results indicated the possibility and applicability of these models to predict soil soluble Ni concentration by soil properties.

Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments

DEFF Research Database (Denmark)

Madsen, Cecilie Maria; Feng, Kung-I; Leithead, Andrew

2018-01-01

The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess...... studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound....

pH-metric solubility. 3. Dissolution titration template method for solubility determination.

Science.gov (United States)

Avdeef, A; Berger, C M

2001-12-01

The main objective of this study was to develop an effective potentiometric saturation titration protocol for determining the aqueous intrinsic solubility and the solubility-pH profile of ionizable molecules, with the specific aim of overcoming incomplete dissolution conditions, while attempting to shorten the data collection time. A modern theory of dissolution kinetics (an extension of the Noyes-Whitney approach) was applied to acid-base titration experiments. A thermodynamic method was developed, based on a three-component model, to calculate interfacial, diffusion-layer, and bulk-water reactant concentrations in saturated solutions of ionizable compounds perturbed by additions of acid/base titrant, leading to partial dissolution of the solid material. Ten commercial drugs (cimetidine, diltiazem hydrochloride, enalapril maleate, metoprolol tartrate, nadolol, propoxyphene hydrochloride, quinine hydrochloride, terfenadine, trovafloxacin mesylate, and benzoic acid) were chosen to illustrate the new titration methodology. It was shown that the new method is about 10 times faster in determining equilibrium solubility constants, compared to the traditional saturation shake-flask methods.

Sibutramine characterization and solubility, a theoretical study

Science.gov (United States)

Aceves-Hernández, Juan M.; Nicolás Vázquez, Inés; Hinojosa-Torres, Jaime; Penieres Carrillo, Guillermo; Arroyo Razo, Gabriel; Miranda Ruvalcaba, René

2013-04-01

Solubility data from sibutramine (SBA) in a family of alcohols were obtained at different temperatures. Sibutramine was characterized by using thermal analysis and X-ray diffraction technique. Solubility data were obtained by the saturation method. The van't Hoff equation was used to obtain the theoretical solubility values and the ideal solvent activity coefficient. No polymorphic phenomena were found from the X-ray diffraction analysis, even though this compound is a racemic mixture of (+) and (-) enantiomers. Theoretical calculations showed that the polarisable continuum model was able to reproduce the solubility and stability of sibutramine molecule in gas phase, water and a family of alcohols at B3LYP/6-311++G (d,p) level of theory. Dielectric constant, dipolar moment and solubility in water values as physical parameters were used in those theoretical calculations for explaining that behavior. Experimental and theoretical results were compared and good agreement was obtained. Sibutramine solubility increased from methanol to 1-octanol in theoretical and experimental results.

A study of transformation water - soluble forms of hevy metals at waste incenerator for detoxicationof ash.

Directory of Open Access Journals (Sweden)

Bilets'ka V. А.

2011-11-01

Full Text Available The complex research processes of transformation of soluble forms of heavy metals in sediment interaction with ash. Proved that the adsorption processes of immobilization lead to a significant decrease of soluble forms of heavy metals in the waste.

Solubility of iron from combustion source particles in acidic media linked to iron speciation.

Science.gov (United States)

Fu, Hongbo; Lin, Jun; Shang, Guangfeng; Dong, Wenbo; Grassian, Vichi H; Carmichael, Gregory R; Li, Yan; Chen, Jianmin

2012-10-16

In this study, iron solubility from six combustion source particles was investigated in acidic media. For comparison, a Chinese loess (CL) dust was also included. The solubility experiments confirmed that iron solubility was highly variable and dependent on particle sources. Under dark and light conditions, the combustion source particles dissolved faster and to a greater extent relative to CL. Oil fly ash (FA) yielded the highest soluble iron as compared to the other samples. Total iron solubility fractions measured in the dark after 12 h ranged between 2.9 and 74.1% of the initial iron content for the combustion-derived particles (Oil FA > biomass burning particles (BP) > coal FA). Ferrous iron represented the dominant soluble form of Fe in the suspensions of straw BP and corn BP, while total dissolved Fe presented mainly as ferric iron in the cases of oil FA, coal FA, and CL. Mössbauer measurements and TEM analysis revealed that Fe in oil FA was commonly presented as nanosized Fe(3)O(4) aggregates and Fe/S-rich particles. Highly labile source of Fe in corn BP could be originated from amorphous Fe form mixed internally with K-rich particles. However, Fe in coal FA was dominated by the more insoluble forms of both Fe-bearing aluminosilicate glass and Fe oxides. The data presented herein showed that iron speciation varies by source and is an important factor controlling iron solubility from these anthropogenic emissions in acidic solutions, suggesting that the variability of iron solubility from combustion-derived particles is related to the inherent character and origin of the aerosols themselves. Such information can be useful in improving our understanding on iron solubility from combustion aerosols when they undergo acidic processing during atmospheric transport.

Ideal gas solubilities and solubility selectivities in a binary mixture of room-temperature ionic liquids.

Science.gov (United States)

Finotello, Alexia; Bara, Jason E; Narayan, Suguna; Camper, Dean; Noble, Richard D

2008-02-28

This study focuses on the solubility behaviors of CO2, CH4, and N2 gases in binary mixtures of imidazolium-based room-temperature ionic liquids (RTILs) using 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2mim][Tf2N]) and 1-ethyl-3-methylimidazolium tetrafluoroborate ([C2mim][BF4]) at 40 degrees C and low pressures (approximately 1 atm). The mixtures tested were 0, 25, 50, 75, 90, 95, and 100 mol % [C2mim][BF4] in [C2mim][Tf2N]. Results show that regular solution theory (RST) can be used to describe the gas solubility and selectivity behaviors in RTIL mixtures using an average mixture solubility parameter or an average measured mixture molar volume. Interestingly, the solubility selectivity, defined as the ratio of gas mole fractions in the RTIL mixture, of CO2 with N2 or CH4 in pure [C2mim][BF4] can be enhanced by adding 5 mol % [C2mim][Tf2N].

Polymer-free nanofibers from vanillin/cyclodextrin inclusion complexes: high thermal stability, enhanced solubility and antioxidant property.

Science.gov (United States)

Celebioglu, Asli; Kayaci-Senirmak, Fatma; İpek, Semran; Durgun, Engin; Uyar, Tamer

2016-07-13

Vanillin/cyclodextrin inclusion complex nanofibers (vanillin/CD-IC NFs) were successfully obtained from three modified CD types (HPβCD, HPγCD and MβCD) in three different solvent systems (water, DMF and DMAc) via an electrospinning technique without using a carrier polymeric matrix. Vanillin/CD-IC NFs with uniform and bead-free fiber morphology were successfully produced and their free-standing nanofibrous webs were obtained. The polymer-free CD/vanillin-IC-NFs allow us to accomplish a much higher vanillin loading (∼12%, w/w) when compared to electrospun polymeric nanofibers containing CD/vanillin-IC (∼5%, w/w). Vanillin has a volatile nature yet, after electrospinning, a significant amount of vanillin was preserved due to complex formation depending on the CD types. Maximum preservation of vanillin was observed for vanillin/MβCD-IC NFs which is up to ∼85% w/w, besides, a considerable amount of vanillin (∼75% w/w) was also preserved for vanillin/HPβCD-IC NFs and vanillin/HPγCD-IC NFs. Phase solubility studies suggested a 1 : 1 molar complexation tendency between guest vanillin and host CD molecules. Molecular modelling studies and experimental findings revealed that vanillin : CD complexation was strongest for MβCD when compared to HPβCD and HPγCD in vanillin/CD-IC NFs. For vanillin/CD-IC NFs, water solubility and the antioxidant property of vanillin was improved significantly owing to inclusion complexation. In brief, polymer-free vanillin/CD-IC NFs are capable of incorporating a much higher loading of vanillin and effectively preserve volatile vanillin. Hence, encapsulation of volatile active agents such as flavor, fragrance and essential oils in electrospun polymer-free CD-IC NFs may have potential for food related applications by integrating the particularly large surface area of NFs with the non-toxic nature of CD and inclusion complexation benefits, such as high temperature stability, improved water solubility and an enhanced

Solubility of carbohydrates in heavy water.

Science.gov (United States)

Cardoso, Marcus V C; Carvalho, Larissa V C; Sabadini, Edvaldo

2012-05-15

The solubility of several mono-(glucose and xylose), di-(sucrose and maltose), tri-(raffinose) and cyclic (α-cyclodextrin) saccharides in H(2)O and in D(2)O were measured over a range of temperatures. The solution enthalpies for the different carbohydrates in the two solvents were determined using the vant' Hoff equation and the values in D(2)O are presented here for the first time. Our findings indicate that the replacement of H(2)O by D(2)O remarkably decreases the solubilities of the less soluble carbohydrates, such as maltose, raffinose and α-cyclodextrin. On the other hand, the more soluble saccharides, glucose, xylose, and sucrose, are practically insensitive to the H/D replacement in water. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Directory of Open Access Journals (Sweden)

Varaporn Buraphacheep Junyaprasert

2015-02-01

Full Text Available Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as NanoEdge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

Science.gov (United States)

Hani, Umme; Shivakumar, H G

2014-01-01

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

Water-soluble dietary fibers and cardiovascular disease.

Science.gov (United States)

Theuwissen, Elke; Mensink, Ronald P

2008-05-23

One well-established way to reduce the risk of developing cardiovascular disease (CVD) is to lower serum LDL cholesterol levels by reducing saturated fat intake. However, the importance of other dietary approaches, such as increasing the intake of water-soluble dietary fibers is increasingly recognized. Well-controlled intervention studies have now shown that four major water-soluble fiber types-beta-glucan, psyllium, pectin and guar gum-effectively lower serum LDL cholesterol concentrations, without affecting HDL cholesterol or triacylglycerol concentrations. It is estimated that for each additional gram of water-soluble fiber in the diet serum total and LDL cholesterol concentrations decrease by -0.028 mmol/L and -0.029 mmol/L, respectively. Despite large differences in molecular structure, no major differences existed between the different types of water-soluble fiber, suggesting a common underlying mechanism. In this respect, it is most likely that water-soluble fibers lower the (re)absorption of in particular bile acids. As a result hepatic conversion of cholesterol into bile acids increases, which will ultimately lead to increased LDL uptake by the liver. Additionally, epidemiological studies suggest that a diet high in water-soluble fiber is inversely associated with the risk of CVD. These findings underlie current dietary recommendations to increase water-soluble fiber intake.

Solubility classification of airborne products from uranium ores and tailings piles

International Nuclear Information System (INIS)

Kalkwarf, D.R.

1979-01-01

Airborne products generated at uranium mills were assigned solubility classifications for use in the ICRP Task Group Lung Model. No significant difference was seen between the dissolution behavior of airborne samples and sieved ground samples of the same product. If the product contained radionuclides that dissolved at different rates, composite classifications were assigned to show the solubility class of each component. If the dissolution data indicated that a radionuclide was present in two chemical forms that dissolved at different rates, a mixed classification was assigned to show the percentage of radionuclide in each solubility class. Uranium-ore dust was assigned the composite classification: ( 235 U, 238 U) W; ( 226 Ra) 10% D, 90% Y; ( 230 Th, 210 Pb, 210 Po) Y. Tailings-pile dust was classified: ( 226 Ra) 10% D, 90% Y; ( 230 Th, 210 Pb, 210 Po) Y. Uranium octoxide was classified Y, uranium tetrafluoride was also classified Y, ammonium diuranate was classified D, and yellow-cake dust was classified ( 235 U, 238 U) 60% D, 40% W. The term yellow cake, however, covers a variety of materials which differ significantly in dissolution rate. Solubility classifications based on the dissolution half-times of particular yellow-cake products should, thus, be used when available. The D, W, and Y classifications refer to biological half-times for clearance from the human respiratory tract of 0 to 10 days, 11 to 100 days, and > 100 days, respectively

Solubility of krypton in hydrofracture grout at elevated pressures

International Nuclear Information System (INIS)

Fitzgerald, C.L.; Mailen, J.C.

1982-01-01

The solubilities of krypton in water, simulated waste solution, and simulated grout at about 25 0 C and to pressures of 150 atm have been determined. The results of these studies show that preliminary calculations of krypton solubility based on the aqueous component of the hydrofracture grout were overly pessimistic. The volume of noble gas generated annually by the reference reprocessing plant would be soluble in the annual hydrofracture grout injection at ORNL at about 10 atm. The amount of krypton in the gas phase would depend on the amount of air in the hydrofracture grout mixture. At 34 atm, and with a small air volume relative to the injected krypton, the krypton would constitute about 30% of the gas bubbles. The disposal of krypton via injection with hydrofracture grout seems to be a viable process. The next logical steps would be to determine the krypton diffusion rate at injection conditions, and possibly to perform a test injection. At present, the schedule for future work is uncertain since funds for this project have been reduced significantly

Transport of soluble species in backfill and rock

International Nuclear Information System (INIS)

Chambre, P.L.; Lee, W.W.L.; Light, W.B.; Pigford, T.H.

1992-03-01

In this report we study the release and transport of soluble species from spent nuclear fuel. By soluble species we mean a fraction of certain fission product species. Our previously developed methods for calculating release rates of solubility-limited species need to be revised for these soluble species. Here we provide methods of calculating release rates of soluble species directly into rock and into backfill and then into rock. Section 2 gives a brief discussion of the physics of fission products dissolution from U0 2 spent fuel. Section 3 presents the mathematics for calculating release rates of soluble species into backfill and then into rock. The calculation of release rates directly into rock is a special case. Section 4 presents numerical illustrations of the analytic results

Speciation and Oxidative Stability of Alkaline Soluble, Non-Pertechnetate Technetium

Energy Technology Data Exchange (ETDEWEB)

Levitskaia, Tatiana G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rapko, Brian M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Anderson, Amity [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Peterson, James M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chatterjee, Sayandev [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Walter, Eric D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Cho, Herman M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Washton, Nancy M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-09-30

The long half-life, complex chemical behavior in tank waste, limited incorporation in mid- to high-temperature immobilization processes, and high mobility in subsurface environments make technetium (Tc) one of the most difficult contaminants to dispose of and/or remediate. Technetium exists predominantly in the liquid tank waste phase as the relatively mobile form of pertechnetate, TcO₄^-. However, based on experimentation to date a significant fraction of the soluble Tc cannot be effectively separated from the wastes and may be present as a non- pertechnetate species. The presence of a non-pertechnetate species significantly complicates disposition of low-activity waste (LAW), and the development of methods to either convert them to pertechnetate or to separate directly is needed. The challenge is the uncertainty regarding the chemical form of the alkaline-soluble low-valent non-pertechnetate species in the liquid tank waste. This report summarizes work done in fiscal year (FY) 2014 exploring the chemistry of a low-valence technetium(I) species, [(CO)₃Tc(H₂O)₃]⁺, a compound of interest due to its implication in the speciation of alkaline-soluble technetium in several Hanford tank waste supernatants.

The physicochemical properties and solubility of pharmaceuticals – Methyl xanthines

International Nuclear Information System (INIS)

Pobudkowska, Aneta; Domańska, Urszula; Kryska, Justyna A.

2014-01-01

the decomposition of Ph at high temperature. The important property tested was the constant acidity, to this end, the spectrophotometric method of Bates–Schwarzenbach was used. Unfortunately, with this method it was not possible to determine the value of pK a 7-(β-hydroxyethyl) theophylline. For other Phs, these values do not differ significantly from those proposed in the literature. Both awareness and knowledge of values of the drug pK a and solubility are important in Phs production. This allows the selection of a suitable solvent and allows estimation of the correct dose and its capacity to absorb in human body

Solubility limits on radionuclide dissolution

Energy Technology Data Exchange (ETDEWEB)

Kerrisk, J.F.

1984-12-31

This paper examines the effects of solubility in limiting dissolution rates of a number of important radionuclides from spent fuel and high-level waste. Two simple dissolution models were used for calculations that would be characteristics of a Yucca Mountain repository. A saturation-limited dissolution model, in which the water flowing through the repository is assumed to be saturated with each waste element, is very conservative in that it overestimates dissolution rates. A diffusion-limited dissolution model, in which element-dissolution rates are limited by diffusion of waste elements into water flowing past the waste, is more realistic, but it is subject to some uncertainty at this time. Dissolution rates of some elements (Pu, Am, Sn, Th, Zr, Sm) are always limited by solubility. Dissolution rates of other elements (Cs, Tc, Np, Sr, C, I) are never solubility limited; their release would be limited by dissolution of the bulk waste form. Still other elements (U, Cm, Ni, Ra) show solubility-limited dissolution under some conditions. 9 references, 3 tables.

Water-soluble vitamins.

Science.gov (United States)

Konings, Erik J M

2006-01-01

combination of enzymes and reaction conditions may vary depending on the composition of the food. Padrangi and Laborde showed recently that treatment with alpha-amylase had no significant effect on measured folate in spinach, although addition of protease significantly increased the release of folate. LC/MS applications gain increasing attention because of their specificity. Rychlik used stable isotope dilution assays for the determination of the folate content of broccoli and bread. Compared to data in the literature and food data bases, amounts were significantly lower. Pawlosky et al., however, found comparable values for 5-methyltetrahydrofolic acid and folic acid by HPLC analysis with fluorescent detection and HPLC/MS. Among samples analyzed were CRMs and broccoli. Besides folic acid, other water-soluble vitamins were also determined by LC/MS/MS by Leporati et al. The method was applied to the quantitative analysis of the natural content of vitamins in typical Italian pasta samples, as well as in fortified pasta samples produced for the U.S. market. Biotin.-A paper from Staggs et al. included the assertion that existing biotin data in food composition tables are inaccurate because the majority are based on bioassays with all relevant disadvantages. Data in most cases are overestimated with consequences for recommendations for dietary biotin intake. An HPLC/avidin-binding assay was used to analyze 87 foods to support the hypothesis mentioned.

[Improvement of Phi bodies stain and its clinical significance].

Science.gov (United States)

Gong, Xu-Bo; Lu, Xing-Guo; Yan, Li-Juan; Xiao, Xi-Bin; Wu, Dong; Xu, Gen-Bo; Zhang, Xiao-Hong; Zhao, Xiao-Ying

2009-02-01

The aim of this study was to improve the dyeing method of hydroperoxidase (HPO), to analyze the morphologic features of Phi bodies and to evaluate the clinical application of this method. 128 bone marrow or peripheral blood smears from patients with myeloid and lymphoid malignancies were stained by improved HPO staining. The Phi bodies were observed with detection rate of Phi bodies in different leukemias. 69 acute myeloid leukemia (AML) specimens were chosen randomly, the positive rate and the number of Phi bodies between the improved HPO and POX stain based on the same substrate of 3, 3'diaminobenzidine were compared. The results showed that the shape of bundle-like Phi bodies was variable, long or short. while the nubbly Phi bodies often presented oval and smooth. Club-like Phi bodies were found in M(3). The detection rates of bundle-like Phi bodies in AML M(1)-M(5) were 42.9% (6/14), 83.3% (15/18), 92.0% (23/25), 52.3% (11/21), 33.3% (5/15) respectively, and those of nubbly Phi bodies were 28.6% (4/14), 66.7% (12/18), 11.1% (3/25), 33.3% (7/21), 20.0% (3/15) respectively. The detection rate of bundle-like Phi bodies in M(3) was significantly higher than that in (M(1) + M(2)) or (M(4) + M(5)) groups. The detection rate of nubbly Phi bodies in (M(1) + M(2)) group was higher than that in M(3) group. In conclusion, after improvement of staining method, the HPO stain becomes simple, the detection rate of Phi bodies is higher than that by the previous method, the positive granules are more obvious, and the results become stable. This improved method plays an important role in differentiating AML from ALL, subtyping AML, and evaluating the therapeutic results.

Sizes of water-soluble luminescent quantum dots measured by fluorescence correlation spectroscopy

International Nuclear Information System (INIS)

Zhang Pudun; Li Liang; Dong Chaoqing; Qian Huifeng; Ren Jicun

2005-01-01

In this paper, fluorescence correlation spectroscopy (FCS) was applied to measure the size of water-soluble quantum dots (QDs). The measurements were performed on a home-built FCS system based on the Stokes-Einstein equation. The obtained results showed that for bare CdTe QDs the sizes from FCS were larger than the ones from transmission electron microscopy (TEM). The brightness of QDs was also evaluated using FCS technique. It was found that the stability of the surface chemistry of QDs would be significantly improved by capping it with hard-core shell. Our data demonstrated that FCS is a simple, fast, and effective method for characterizing the fluorescent quantum dots, and is especially suitable for determining the fluorescent nanoparticles less than 10 nm in water solution

Solubility of Copper(II Sulfate and Dicopper Chloride Trihydroxide for Pigs

Directory of Open Access Journals (Sweden)

C. S. Park

2016-11-01

Full Text Available This study was conducted to determine the solubility of copper (Cu in two sources of copper(II sulfate (CuSO4 including monohydrate and pentahydrate and three sources of dicopper chloride trihydroxide (dCCTH including α-form (dCCTH-α, β-form (dCCTH-β, and a mixture of α- and β-form (dCCTH-αβ at different pH and a 3-step in vitro digestion assay for pigs. In Exp. 1, Cu sources were incubated in water-based buffers at pH 2.0, 3.0, 4.8, and 6.8 for 4 h using a shaking incubator at 39°C. The CuSO4 sources were completely dissolved within 15 min except at pH 6.8. The solubility of Cu in dCCTH-α was greater (p<0.05 than dCCTH-β but was not different from dCCTH-αβ during 3-h incubation at pH 2.0 and during 2-h incubation at pH 3.0. At pH 4.8, there were no significant differences in solubility of Cu in dCCTH sources. Copper in dCCTH sources were non-soluble at pH 6.8. In Exp. 2, the solubility of Cu was determined during the 3-step in vitro digestion assay for pigs. All sources of Cu were completely dissolved in step 1 which simulated digestion in the stomach. In Exp. 3, the solubility of Cu in experimental diets including a control diet and diets containing 250 mg/kg of additional Cu from five Cu sources was determined during the in vitro digestion assay. The solubility of Cu in diets containing additional Cu sources were greater (p<0.05 than the control diet in step 1. In conclusion, the solubility of Cu was influenced by pH of digesta but was not different among sources based on the in vitro digestion assay.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives.

Science.gov (United States)

Saluja, Hardeep; Mehanna, Ahmed; Panicucci, Riccardo; Atef, Eman

2016-06-01

The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives

Directory of Open Access Journals (Sweden)

Hardeep Saluja

2016-06-01

Full Text Available The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP and droperidol (DP and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

Synthesis of novel core-shell structured dual-mesoporous silica nanospheres and their application for enhancing the dissolution rate of poorly water-soluble drugs

Energy Technology Data Exchange (ETDEWEB)

Wu, Chao, E-mail: wuchao27@126.com [Department of Pharmaceutics, Liaoning Medical University, 40 Songpo Road, Linghe District, Jinzhou, Liaoning Province 121001 (China); Sun, Xiaohu [Management Center for Experiments, Bohai University, 19 Keji Road, Songshan District, Jinzhou, Liaoning Province 121000 (China); Zhao, Zongzhe; Zhao, Ying; Hao, Yanna; Liu, Ying [Department of Pharmaceutics, Liaoning Medical University, 40 Songpo Road, Linghe District, Jinzhou, Liaoning Province 121001 (China); Gao, Yu, E-mail: gaoyu_1116@163.com [Department of Medical Oncology, First Affiliated Hospital of Liaoning Medical University, 40 Songpo Road, Linghe District, Jinzhou, Liaoning Province 121001 (China)

2014-11-01

Novel core-shell dual-mesoporous silica nanospheres (DMSS) with a tunable pore size were synthesized successfully using a styrene monomer as a channel template for the core and cetyltrimethyl ammonium bromide (CTAB) as a channel template for the shell in order to improve the dissolution rate of poorly water-soluble drugs. Simvastatin was used as a model drug and loaded into DMSS and the mesoporous core without the shell (MSC) by the solvent evaporation method. The drug loading efficiency of DMSS and MSC were determined by thermogravimetric analysis (TGA) and ultraviolet spectroscopy (UV). Characterization, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) showed that simvastatin adsorbed in DMSS and MSC was in an amorphous state, and in vitro release test results demonstrated that both DMSS and MSC increased the water solubility and dissolution rate of simvastatin. The shell structure of DMSS was able to regulate the release of simvastatin compared with MSC. It is worth noting that DMSS has significant potential as a carrier for improving the dissolution of poorly water-soluble drugs and reducing the rapid release. - Highlights: • A novel core-shell DMSS is prepared for improving the dissolution rate of simvastatin. • The diffusional resistance of the mesoporous shell can delay and regulate drug release. • Simvastatin absorbed in DMSS exists in amorphous form due to spatial confinement.

Synthesis of novel core-shell structured dual-mesoporous silica nanospheres and their application for enhancing the dissolution rate of poorly water-soluble drugs

International Nuclear Information System (INIS)

Wu, Chao; Sun, Xiaohu; Zhao, Zongzhe; Zhao, Ying; Hao, Yanna; Liu, Ying; Gao, Yu

2014-01-01

Novel core-shell dual-mesoporous silica nanospheres (DMSS) with a tunable pore size were synthesized successfully using a styrene monomer as a channel template for the core and cetyltrimethyl ammonium bromide (CTAB) as a channel template for the shell in order to improve the dissolution rate of poorly water-soluble drugs. Simvastatin was used as a model drug and loaded into DMSS and the mesoporous core without the shell (MSC) by the solvent evaporation method. The drug loading efficiency of DMSS and MSC were determined by thermogravimetric analysis (TGA) and ultraviolet spectroscopy (UV). Characterization, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) showed that simvastatin adsorbed in DMSS and MSC was in an amorphous state, and in vitro release test results demonstrated that both DMSS and MSC increased the water solubility and dissolution rate of simvastatin. The shell structure of DMSS was able to regulate the release of simvastatin compared with MSC. It is worth noting that DMSS has significant potential as a carrier for improving the dissolution of poorly water-soluble drugs and reducing the rapid release. - Highlights: • A novel core-shell DMSS is prepared for improving the dissolution rate of simvastatin. • The diffusional resistance of the mesoporous shell can delay and regulate drug release. • Simvastatin absorbed in DMSS exists in amorphous form due to spatial confinement

Hydrogen solubility in austenite of Fe-Ni-Cr alloys

International Nuclear Information System (INIS)

Zhirnova, V.V.; Mogutnov, B.M.; Tomilin, I.A.

1981-01-01

Hydrogen solubility in Fe-Ni-Cr alloys at 600-1000 deg C is determined. Hydrogen solubility in ternary alloys can not be predicted on the basis of the data on its solubility in binary Fe-Ni, Fe-Cr alloys. Chromium and nickel effect on hydrogen solubility in iron is insignificant in comparison with the effect of these elements on carbon or nitrogen solubility [ru

Water-soluble coenzyme Q10 formulation in presbycusis: long-term effects.

Science.gov (United States)

Guastini, Luca; Mora, Renzo; Dellepiane, Massimo; Santomauro, Valentina; Giorgio, Manini; Salami, Angelo

2011-05-01

These findings provide the basis for understanding the duration of the effect after the last use of the drug and encourage a larger clinical trial to collect additional evidence on the effect of coenzyme Q10 (CoQ10) in preventing the development of hearing loss in subjects with presbycusis. The aim of this study was to evaluate the long-term effects of a water-soluble formulation of CoQ10 (Q-TER) in subjects with presbycusis. Sixty patients with presbycusis were included and divided at random into three numerically equal groups. For 30 days, group A underwent therapy with Q-TER, group B underwent therapy with vitamin E, and group C received placebo. Before, at the end, and 6 months after the end of the treatment, all patients underwent evaluation of pure tone audiometry, transient evoked otoacoustic emissions and otoacoustic products of distortion, auditory brainstem response, and speech audiometry. Compared with group B, at the end of the treatment in group A the pure tone audiometry showed a significant (p < 0.05) improvement of the audiometric thresholds at 1000, 2000, 4000, and 8000 Hz. This improvement was confirmed by the speech audiometry and last check. We found no significant differences in the other parameters and in group C.

Carcinogenicity assessment of water-soluble nickel compounds.

Science.gov (United States)

Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Refuse derived soluble bio-organics enhancing tomato plant growth and productivity

Energy Technology Data Exchange (ETDEWEB)

Sortino, Orazio [Dipartimento di Scienze Agronomiche Agrochimiche e delle Produzioni Animali, Universita degli Studi di Catania, Via Valdisavoia 5, 95123 Catania (Italy); Dipasquale, Mauro [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Montoneri, Enzo, E-mail: enzo.montoneri@unito.it [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Tomasso, Lorenzo; Perrone, Daniele G. [Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino (Italy); Vindrola, Daniela; Negre, Michele; Piccone, Giuseppe [Dipartimento di Valorizzazione e Protezione delle Risorse Agroforestali, Universita di Torino, Via L. da Vinci 44, 10095 Grugliasco (Italy)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Municipal bio-wastes are a sustainable source of bio-based products. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics promote chlorophyll synthesis. Black-Right-Pointing-Pointer Refuse derived soluble bio-organics enhance plant growth and fruit ripening rate. Black-Right-Pointing-Pointer Sustainable chemistry exploiting urban refuse allows sustainable development. Black-Right-Pointing-Pointer Chemistry, agriculture and the environment benefit from biowaste technology. - Abstract: Municipal bio-refuse (CVD), containing kitchen wastes, home gardening residues and public park trimmings, was treated with alkali to yield a soluble bio-organic fraction (SBO) and an insoluble residue. These materials were characterized using elemental analysis, potentiometric titration, and 13C NMR spectroscopy, and then applied as organic fertilizers to soil for tomato greenhouse cultivation. Their performance was compared with a commercial product obtained from animal residues. Plant growth, fruit yield and quality, and soil and leaf chemical composition were the selected performance indicators. The SBO exhibited the best performance by enhancing leaf chlorophyll content, improving plant growth and fruit ripening rate and yield. No product performance-chemical composition relationship could be assessed. Solubility could be one reason for the superior performance of SBO as a tomato growth promoter. The enhancement of leaf chlorophyll content is discussed to identify a possible link with the SBO photosensitizing properties that have been demonstrated in other work, and thus with photosynthetic performance.

Refuse derived soluble bio-organics enhancing tomato plant growth and productivity

International Nuclear Information System (INIS)

Sortino, Orazio; Dipasquale, Mauro; Montoneri, Enzo; Tomasso, Lorenzo; Perrone, Daniele G.; Vindrola, Daniela; Negre, Michele; Piccone, Giuseppe

2012-01-01

Highlights: ► Municipal bio-wastes are a sustainable source of bio-based products. ► Refuse derived soluble bio-organics promote chlorophyll synthesis. ► Refuse derived soluble bio-organics enhance plant growth and fruit ripening rate. ► Sustainable chemistry exploiting urban refuse allows sustainable development. ► Chemistry, agriculture and the environment benefit from biowaste technology. - Abstract: Municipal bio-refuse (CVD), containing kitchen wastes, home gardening residues and public park trimmings, was treated with alkali to yield a soluble bio-organic fraction (SBO) and an insoluble residue. These materials were characterized using elemental analysis, potentiometric titration, and 13C NMR spectroscopy, and then applied as organic fertilizers to soil for tomato greenhouse cultivation. Their performance was compared with a commercial product obtained from animal residues. Plant growth, fruit yield and quality, and soil and leaf chemical composition were the selected performance indicators. The SBO exhibited the best performance by enhancing leaf chlorophyll content, improving plant growth and fruit ripening rate and yield. No product performance-chemical composition relationship could be assessed. Solubility could be one reason for the superior performance of SBO as a tomato growth promoter. The enhancement of leaf chlorophyll content is discussed to identify a possible link with the SBO photosensitizing properties that have been demonstrated in other work, and thus with photosynthetic performance.

Solubility study of Tc(IV) oxides

International Nuclear Information System (INIS)

Liu, D.J.; Fan, X.H.

2005-01-01

The deep geological disposal of the high level radioactive wastes is expected to be a safer disposal method in most countries. The long-lived fission product 99 Tc is present in large quantities in nuclear wastes and its chemical behavior in aqueous solution is of considerable interest. Under oxidizing conditions technetium exists as the anionic species TcO 4 - whereas under the reducing conditions, expected to exist in a deep geological repository, it is generally predicted that technetium will be present as TcO 2 ·nH 2 O. Hence, the mobility of Tc(IV) in reducing groundwater may be limited by the solubility of TcO 2 ·nH 2 O under these conditions. Due to this fact it is important to investigate the solubility of TcO 2 ·nH 2 O. The solubility determines the release of radionuclides from waste form and is used as a source term in radionuclide migration analysis in performance assessment of radioactive waste repository. Technetium oxide was prepared by reduction of a technetate solution with Sn 2 + . The solubility of Tc(IV) oxide has been determined in simulated groundwater and redistilled water under aerobic and anaerobic conditions. The effects of pH and CO 3 2- concentration of solution on solubility of Tc(IV) oxide were studied. The concentration of total technetium and Tc(IV) species in the solutions were periodically determined by separating the oxidized and reduced technetium species using a solvent extraction procedure and counting the beta activity of the 99 Tc with a liquid scintillation counter. The experimental results show that the rate of oxidation of Tc(IV) in simulated groundwater and redistilled water is about (1.49-1.86) x 10 -9 mol/(L·d) under aerobic conditions, but Tc(IV) in simulated groundwater and redistilled water is not oxidized under anaerobic conditions. Under aerobic or anaerobic conditions the solubility of Tc(IV) oxide in simulated groundwater and redistilled water is equal on the whole after centrifugation or ultrafiltration. The

Aqueous solubility, dispersibility and toxicity of biodiesels

International Nuclear Information System (INIS)

Hollebone, B.P.; Fieldhouse, B.; Lumley, T.C.; Landriault, M.; Doe, K.; Jackman, P.

2007-01-01

The renewed interest in the use of biological fuels can be attributed to that fact that feedstocks for fatty-acid ester biodiesels are renewable and can be reclaimed from waste. Although there are significant benefits to using biodiesels, their increased use leaves potential for accidental release to the environment. Therefore, their environmental behaviours and impacts must be evaluated along with the risk associated with their use. Biodiesel fuels may be made from soy oil, canola oil, reclaimed restaurant grease, fish oil and animal fat. The toxicological fate of biofuel depends on the variability of its chemical composition. This study provided an initial assessment of the aqueous fate and effects of biodiesel from a broad range of commonly available feedstocks and their blends with petroleum diesels. The study focused primarily on the fate and impact of these fuels in fresh-water. The use of chemical dispersion as a countermeasure for saltwater was also investigated. The exposure of aquatic ecosystems to biodiesels and petroleum diesel occurs via the transfer of material from the non-aqueous phase liquid (NAPL) into the aqueous phase, as both soluble and dispersed components. The aqueous solubilities of the fuels were determined from the equilibrium water-accommodated fraction concentrations. The acute toxicities of many biodiesels were reported for 3 test species used by Environment Canada for toxicological evaluation, namely rainbow trout, the water flea and a luminescent bacterium. This study also evaluated the natural potential for dispersion of the fuels in the water column in both low and high-energy wave conditions. Chemical dispersion as a potential countermeasure for biodiesel spills was also evaluated using solubility testing, acute toxicity testing, and dispersibility testing. It was shown that biodiesels have much different fates and impacts from petroleum diesels. The compounds partitioning into the water column are also very different for each

Soluble Moringa oleifera leaf extract reduces intracellular cadmium accumulation and oxidative stress in Saccharomyces cerevisiae.

Science.gov (United States)

Kerdsomboon, Kittikhun; Tatip, Supinda; Kosasih, Sattawat; Auesukaree, Choowong

2016-05-01

Moringa oleifera leaves are a well-known source of antioxidants and traditionally used for medicinal applications. In the present study, the protective action of soluble M. oleifera leaf extract (MOLE) against cadmium toxicity was investigated in the model eukaryote Saccharomyces cerevisiae. The results showed that this extract exhibited a protective effect against oxidative stress induced by cadmium and H2O2 through the reduction of intracellular reactive oxygen species. Interestingly, not only the co-exposure of soluble MOLE with cadmium but also pretreatment of this extract prior to cadmium exposure significantly reduced the cadmium uptake through an inhibition of Fet4p, a low-affinity iron(II) transporter. In addition, the supplementation of soluble MOLE significantly reduced intracellular iron accumulation in a Fet4p-independent manner. Our findings suggest the potential use of soluble extract from M. oleifera leaves as a dietary supplement for protection against cadmium accumulation and oxidative stress. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Solubility of cefoxitin acid in different solvent systems

International Nuclear Information System (INIS)

Yuan, Fuhong; Wang, Yongli; Xiao, Liping; Huang, Qiaoyin; Xu, Jinchao; Jiang, Chen; Hao, Hongxun

2016-01-01

Highlights: • The solubility of cefoxitin acid in different solvent systems was measured. • Three models were used to correlate the solubility data. • The dissolution enthalpy of the dissolution process was calculated. - Abstract: Cefoxitin acid is one kind of important pharmaceutical intermediate. Its solubility is crucial for designing and optimizing the crystallization processes. In this work, the solubility of cefoxitin acid in organic solvents (methanol, acetonitrile, ethanol, isopropanol, n-propanol and ethyl acetate), water and water-methanol mixtures was measured spectrophotometrically using a shake-flask method within the temperature range 278.15–303.15 K. PXRD data and the Karl Fischer method were used to verify the crystal form stability of cefoxitin acid in the solubility measuring process. The melting points, the enthalpy and entropy of fusion were estimated. Results showed that the solubility of cefoxitin acid increases with the increasing temperature in all tested solvents in this work, and the solubility of cefoxitin acid increases with the increasing methanol concentration in water-methanol mixtures. The experimental solubility values were well correlated using the modified Apelblat equation, NRTL model and CNIBS/R-K model. An equation proposed by Williamson was adopted to calculate the molar enthalpy during the dissolution process.

Effects of gamma irradiation on physicochemical properties of heat-induced gel prepared with chicken salt-soluble proteins

International Nuclear Information System (INIS)

Choi, Yun-Sang; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Jeong, Tae-Jun; Seo, Kwang-Wook; Kim, Young-Boong; Kim, Cheon-Jei

2015-01-01

The technological effects of gamma irradiation (0, 3, 7, and 10 kGy) on chicken salt-soluble meat proteins in a model system were investigated. There were no significant differences in protein, fat, and ash content, and sarcoplasmic protein solubility among all samples. The samples with increasing gamma irradiation levels had higher pH, lightness, yellowness, and apparent viscosity, whereas moisture content, water holding capacity, redness, myofibrillar protein solubility, total protein solubility, hardness, springiness, cohesiveness, gumminess, and chewiness were the highest in the unirradiated control. The result from meat products using gamma irradiation was intended to provide a basic resource processing technology. - Highlights: • The effect of gamma irradiation on salt-soluble meat proteins was investigated. • Gelling properties of salt-soluble protein affected by gamma irradiation. • Gamma irradiation of meat products provides a basic resource processing technology

Study of solubility of some metal cyclohexane carbonates

International Nuclear Information System (INIS)

Niyazov, A.N.; Amanov, K.B.; Trapeznikova, V.F.; Kul'maksimov, A.; Kolosova, N.

1978-01-01

The solubility of calcium, magnesium, strontium, barium, cabalt, copper and aluminium cyclohexane, carbonates (CHC) in water has been studied at 25 deg C. The salt solubility has been calculated according to the metal ion concentration in saturated solutions. It has been established, that the cobalt and rare earth cyclohexane carbonates are relatively very soluble in water and have solubility products of SP > 1x10 -5 . The solubility of CHC of multivalent metals increases with the decrease of pH values. Each salt has some ''limiting'' pH value of a solution, below which it decomposes completely and can not exist in a solution in the form of solid phase

Hydrothermal solubility of uraninite. Final technical report

International Nuclear Information System (INIS)

Parks, G.A.; Pohl, D.C.

1985-01-01

Experimental measurements of the solubility of UO 2 from 100 to 300 0 C under 500 bars H 2 , in NaCl solutions at pH from 1 to 8 do not agree with solubilities calculated using existing thermodynamic databases. For pH 2 (hyd) has precipitated and is controlling solubility. For pH > 8, solubilities at all temperatures are much lower than predicted, suggesting that the U(OH)/sub delta/ - complex is much weaker than predicted. Extrapolated to 25 0 C, high pH solubility agrees within experimental error with the upper limit suggested by Ryan and Rai (1983). In the pH range 2 to 6, solubilities are up to three orders of magnitude lower than predicted for temperatures exceeding 200 0 C and up to two orders higher than predicted at lower temperatures. pH dependence in this region is negligible suggesting that U(OH) 4 (aq) predominates, thus the stability of this species is higher than presently estimated at low temperatures, but the enthalpy of solution is smaller. A low maximum observed near pH approx. =3 is presently unexplained. 40 refs., 16 figs., 12 tabs

Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15.

Science.gov (United States)

Rajebahadur, Minal; Zia, Hossein; Nues, Anthony; Lee, Chong

2006-01-01

The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.

Predictive value of serum soluble corin in the risk of hyperglycemia: A population-based prospective cohort study in China.

Science.gov (United States)

Zhu, Zhengbao; Zhang, Qiu; Peng, Hao; Zhong, Chongke; Guo, Daoxia; Huangfu, Xinfeng; Chao, Xiangqin; Wang, Aili; Jin, Jianhua; Zhang, Yonghong

2018-04-01

Serum soluble corin has been suggested to be associated with hyperglycemia by cross-sectional study. However, the prospective relationship between them remains unclear, and whether lipid component influences the relationship between them has not yet been studied. A total of 1961 participants who were free from hyperglycemia were enrolled at baseline in 2010. The serum soluble corin concentrations were measured at baseline and all participants were followed up for hyperglycemia in 2014. The association between serum soluble corin and hyperglycemia incidence was appreciably modified by high density lipoprotein cholesterol (HDL-C) (P interaction  = 0.04). Elevated serum soluble corin was associated with the risk of hyperglycemia only in the HDL-C ≥1.04 mmol/l subgroup rather than all participants. In participants with HDL-C ≥1.04 mmol/l, the adjusted odds ratio (95% CU) of hyperglycemia associated with the fourth quartiles of corin was 1.78 (1.08-2.94) compared with the lowest quartile of serum soluble corin, and there was a positive linear dose-response relationship between them (P for linearity <0.01). The ordinal analysis showed an association between serum soluble corin and hyperglycemia severity (adjusted OR, 1.81; 95% CI, 1.10-2.99; P trend  = 0.02, when 2 extreme quartiles were compared). The addition of serum soluble corin to conventional risk factors improved risk prediction for hyperglycemia (net reclassification index: 0.16; integrated discrimination improvement: 0.01) in participants with HDL-C ≥1.04 mmol/l. Serum soluble corin might be a valuable biomarker in prediction of future hyperglycemia in population with HDL-C ≥1.04 mmol/l, suggesting that corin might play a potential role in glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Diffusion and solubility coefficients determined by permeation and immersion experiments for organic solvents in HDPE geomembrane.

Science.gov (United States)

Chao, Keh-Ping; Wang, Ping; Wang, Ya-Ting

2007-04-02

The chemical resistance of eight organic solvents in high density polyethylene (HDPE) geomembrane has been investigated using the ASTM F739 permeation method and the immersion test at different temperatures. The diffusion of the experimental organic solvents in HDPE geomembrane was non-Fickian kinetic, and the solubility coefficients can be consistent with the solubility parameter theory. The diffusion coefficients and solubility coefficients determined by the ASTM F739 method were significantly correlated to the immersion tests (pHDPE as barriers in the field.

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

Science.gov (United States)

Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

2017-01-01

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus ® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus ® , when protected from moisture.

Synthesis, characterization and solubility of a new anthelmintic salt: Mebendazole nitrate

Science.gov (United States)

Gutiérrez, Eduardo L.; Souza, Matheus S.; Diniz, Luan F.; Ellena, Javier

2018-06-01

Salt formation approach was taken to improve Mebendazole (MBZ) solubility. MBZ polymorph A was easily recrystallized as a 1:1 nitrate salt (MBZ N) in methanol. Single crystal X-ray diffraction data show that MBZ N crystallizes in the P 1 bar space group. By strong intermolecular H-bonding interactions, MBZ is associated with a nitrate anion forming a supramolecular R22(8) synthon. Crystal packing is stabilized by these H-bonds, through which each nitrate connects two molecules of MBZ forming chains along the b axis. The vibrational behavior studied by micro FT-Raman and FT-IR spectroscopy is consistent with the crystal structure. Thermal analysis of the salt indicates that the compound is stable up to 150 °C, when an almost simultaneous elimination of HNO3 and CO2 occurs. MBZ N equilibrium solubility was evaluated in hydrochloric acid 0.1 M solution and compared with those of MBZ A and C. An improvement in a factor of 5 and 1.22 was found respectively.

Comparative in vitro study for orthodontic adhesives relatively to sorption and solubility

Science.gov (United States)

Muntean, A.; Mesaros, A.; Festila, D.; Moldovan, M.; Boboia, S.; Mesaros, M.

2015-12-01

Water sorption and solubility correspond to undesirable physical characteristics because it may cause micro leakage and dissolution for composite materials used for orthodontic attachment bonding. The aim of this study was to evaluate the performance of four composite materials employed in orthodontic as adhesives, relatively to water and 50% alcoholic solution, by means of in vitro tests of sorption and solubility. We used an experimental composite sealer SO® (ICCRR Cluj Napoca) and 3 commercial products already on the market: Blugloo® (Ormco), Opal Bond MV® (Ultradent) and Bond It® (DB orthodontics). Data were recorded and specific statistic tests were performed, revealing significant differences for all materials relatively to tested solutions. The materials expressed an adequate performance in terms of sorption and solubility, offering various alternatives for orthodontists.

Diagnosing solubility limitations – the example of hydrate formation

Directory of Open Access Journals (Sweden)

Joerg Berghausen

2014-07-01

Full Text Available Solubility is regarded as one of the key challenges in many drug discovery projects. Thus, it’s essential to support the lead finding and optimization efforts by appropriate solubility data. In silico solubility prediction remains challenging and therefore a screening assay is used as a first filter, followed by selected follow-up assays to reveal what causes the low solubility of a specific compound or chemotype. Results from diagnosing the underlying reason for solubility limitation are discussed. As lipophilicity and crystal lattice forces are regarded as main contributors to limiting solubility, changes in solid state are important to be recognized. Solubility limitation by various factors will be presented and the impact of the solid-state is exemplified by compounds that are able to form hydrates.

Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D.

Science.gov (United States)

Ke, Zhongcheng; Hou, Xuefeng; Jia, Xiao-Bin

2016-01-01

The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.

Improvement of intestinal absorption of forsythoside A in weeping forsythia extract by various absorption enhancers based on tight junctions.

Science.gov (United States)

Zhou, Wei; Qin, Kun Ming; Shan, Jin Jun; Ju, Wen Zheng; Liu, Shi Jia; Cai, Bao Chang; Di, Liu Qing

2012-12-15

Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no

Drug Solubility in Fatty Acids as a Formulation Design Approach for Lipid-Based Formulations: A Technical Note.

Science.gov (United States)

Lee, Yung-Chi; Dalton, Chad; Regler, Brian; Harris, David

2018-06-06

Lipid-based drug delivery systems have been intensively investigated as a means of delivering poorly water-soluble drugs. Upon ingestion, the lipases in the gastrointestinal tract digest lipid ingredients, mainly triglycerides, within the formulation into monoglycerides and fatty acids. While numerous studies have addressed the solubility of drugs in triglycerides, comparatively few publications have addressed the solubility of drugs in fatty acids, which are the end product of digestion and responsible for the solubility of drug within mixed micelles. The objective of this investigation was to explore the solubility of a poorly water-soluble drug in fatty acids and raise the awareness of the importance of drug solubility in fatty acids. The model API (active pharmaceutical ingredient), a weak acid, is considered a BCS II compound with an aqueous solubility of 0.02 μg/mL and predicted partition coefficient >7. The solubility of API ranged from 120 mg/mL to over 1 g/mL in fatty acids with chain lengths across the range C18 to C6. Hydrogen bonding was found to be the main driver of the solubilization of API in fatty acids. The solubility of API was significantly reduced by water uptake in caprylic acid but not in oleic acid. This report demonstrates that solubility data generated in fatty acids can provide an indication of the solubility of the drug after lipid digestion. This report also highlights the importance of measuring the solubility of drugs in fatty acids in the course of lipid formulation development.

Solubility and degradation of paracetamol in subcritical water

Directory of Open Access Journals (Sweden)

Emire Zuhal

2017-01-01

Full Text Available In this study, solubility and degradation of paracetamol were examined using subcritical water. Effect of temperature and static time was investigated during solubility process in subcritical water at constant pressure (50 bar. Experimental results show that temperature and static time have crucial effect on the degradation and solubility rates. Maximum mole fraction for solubility of paracetamol was obtained at 403 K as (14.68 ± 0.74×103. Approximation model for solubility of paracetamol was proposed. O2 and H2O2 were used in degradation process of paracetamol. Maximum degradation rate was found as 68.66 ± 1.05 and 100 ± 0.00 % using O2 and H2O2, respectively.

Solubility of hydrogen in bio-oil compounds

International Nuclear Information System (INIS)

Qureshi, Muhammad Saad; Touronen, Jouni; Uusi-Kyyny, Petri; Richon, Dominique; Alopaeus, Ville

2016-01-01

Highlights: • Solubility of Hydrogen was measured in bio-oil compounds in the at temperatures from 342 to 473 K and pressures up to 16 MPa. • Phase equilibrium data were acquired using a visualization enabled continuous flow synthetic apparatus. • The measured solubility is modeled with Peng-Robinson EoS. - Abstract: The knowledge of accurate hydrogen solubility values in bio-oil compounds is essential for the design and optimization of hydroprocesses relevant to biofuel industry. This work reports the solubility of hydrogen in three industrially relevant bio-oil compounds (allyl alcohol, furan, and eugenol) at temperatures from 342 to 473 K and pressures up to 16 MPa. Phase equilibrium data were acquired using a continuous flow synthetic method. The method is based on the visual observation of the bubble point using a high resolution camera. The measured solubility is modeled with Peng-Robinson EoS with classical van der Waals one fluid mixing rules.

Separation of three water-soluble vitamins by poly(dimethylsiloxane) microchannel electrophoresis with electrochemical detection.

Science.gov (United States)

Li, Xiang-Yun; Zhang, Qian-Li; Lian, Hong-Zhen; Xu, Jing-Juan; Chen, Hong-Yuan

2007-09-01

A method for rapid separation and sensitive determination of three water-soluble vitamins, pyridoxine, ascorbic acid (VC), and p-aminobenzoic acid (PABA) has been developed by PDMS microchannel electrophoresis integrated with amperometric detection. After treatment of the microchip with oxygen plasma, the peak shapes of the three analytes were essentially improved. Pyridoxine, VC, and PABA were well separated within only 80 s in a running buffer of 20 mM borate solution (pH 8.5). Good linearity was obtained within the concentration range of 2-200 microM for the three water-soluble vitamins. The detection limits were 1.0 microM for pyridoxine and VC, and 1.5 microM for PABA. The proposed method has been successfully applied to real human urine sample, without solid phase extraction, with recoveries of 80-122% for the three water-soluble vitamins.

Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

Science.gov (United States)

Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

2015-01-01

A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

Water sorption and solubility of bulk-fill composites polymerized with a third generation LED LCU

Directory of Open Access Journals (Sweden)

Tuğba MİSİLLİ

2017-10-01

Full Text Available Abstract The aim of this study was to compare the degree of water sorption and solubility in bulk-fills after curing with a polywave light source. A total of 120 disc-shaped specimens (8 mm diameter; 4 mm depth were prepared from three regular bulk-fill materials (X-tra Fil, Tetric N-Ceram Bulk Fill, SonicFill, and a control material (Filtek Z250, cured in 3 different modes (standard: 1000 mW/cm2-20 s; high power: 1400 mW/cm2-12 s; xtra power: 3200 mW/cm2-6 s using a third generation light-emitting diode light curing unit. Water sorption and solubility levels of the specimens were measured according to the ISO 4049:2009 specification after storing in distilled water for 30 days. Data were analyzed using two-way ANOVA and Tukey’s post-hoc test (p < 0.05. The Z250 sample exposed to high power presented a higher sorption compared to the X-tra Fil and SonicFill samples. In xtra power mode, the values of Z250 and SonicFill were similar to each other and higher compared to those of X-tra Fil. Only SonicFill exhibited significantly different sorption values depending on the curing mode, the highest of which was achieved when using the xtra power mode. The highest solubility values were obtained for SonicFill. No statistically significant differences were found among other groups. No significant correlation was detected between water sorption and solubility. The traditional composite group exhibited a higher water sorption values than the bulk-fills. The reduction in polymerization time significantly increased the sorption of SonicFill. SonicFill showed the highest water solubility value among the composites tested.

Solubility and physical properties of sugars in pressurized water

International Nuclear Information System (INIS)

Saldaña, Marleny D.A.; Alvarez, Víctor H.; Haldar, Anupam

2012-01-01

Highlights: ► Sugar solubility in pressurized water and density at high pressures were measured. ► Glucose solubility was higher than that of lactose as predicted by their σ-profiles. ► Sugar aqueous solubility decreased with an increase in pressure from 15 to 120 bar. ► Aqueous glucose molecular packing shows high sensitivity to pressure. ► The COSMO-SAC model qualitatively predicted the sugar solubility data. - Abstract: In this study, the solubility, density, and refractive index of glucose and lactose in water as a function of temperature were measured. For solubility of sugars in pressurized water, experimental data were obtained at pressures of (15 to 120) bar and temperatures of (373 to 433) K using a dynamic flow high pressure system. Density data for aqueous sugar solutions were obtained at pressures of (1 to 300) bar and temperatures of (298 to 343) K. The refractive index of aqueous sugar solutions was obtained at 293 K and atmospheric pressure. Activity coefficient models, Van Laar and the Conductor-like Screening Model-Segment Activity Coefficient (COSMO-SAC), were used to fit and predict the experimental solubility data, respectively. The results obtained showed that the solubility of both sugars in pressurized water increase with an increase in temperature. However, with the increase of pressure from 15 bar to 120 bar, the solubility of both sugars in pressurized water decreased. The Van Laar model fit the experimental aqueous solubility data with deviations lower than 13 and 53% for glucose and lactose, respectively. The COSMO-SAC model predicted qualitatively the aqueous solubility of these sugars.

Evaluation of ascitic soluble human leukocyte antigen-G for distinguishing malignant ascites from benign ascites.

Science.gov (United States)

Sun, Juan; Chang, Yan-Xiang; Niu, Chun-Yan

2017-11-01

The overexpression of soluble human leukocyte antigen-G is associated with malignant tumours. The purpose of our study was to detect soluble human leukocyte antigen-G concentrations in ascites and to evaluate the value of ascitic soluble human leukocyte antigen-G for the diagnosis of malignant ascites. Enzyme-linked immunosorbent assay was used to detect soluble human leukocyte antigen-G levels in 64 patients with malignant ascites and 30 patients with benign ascites. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of ascitic soluble human leukocyte antigen-G for the detection of malignant ascites. Ascitic soluble human leukocyte antigen-G levels were significantly higher in the malignant ascites group than in the benign ascites group (20.718 ± 3.215 versus 12.467 ± 3.678 µg/L, t = 7.425, p human leukocyte antigen-G was 0.957 (95% confidence interval, 0.872-0.992). At a cut-off value of 19.60 µg/L, the sensitivity and specificity of ascitic soluble human leukocyte antigen-G were 87.5% (95% confidence interval, 71.0%-96.5%) and 100% (95% confidence interval, 88.4%-100%), respectively. With respect to area under the receiver operating characteristic curve, sensitivity and specificity, ascitic carcinoembryonic antigen (0.810, 68.75% and 83.33%, respectively) and carbohydrate antigen 19-9 (0.710, 65.63% and 70%, respectively) significantly differed (all p human leukocyte antigen-G was 75%, which was higher than the corresponding rates for ascitic carcinoembryonic antigen (31.25%) and carbohydrate antigen 19-9 (6.25%; both p human leukocyte antigen-G exhibited good performance for diagnosing malignant ascites, and particularly those that were cytology-negative and biopsy-positive.

Effect of Cyclodextrin Complexation on the Aqueous Solubility and Solubility/Dose Ratio of Praziquantel

OpenAIRE

Maragos, Stratos; Archontaki, Helen; Macheras, Panos; Valsami, Georgia

2009-01-01

Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound ...

Research on solubility characteristics of gaseous methyl iodide

International Nuclear Information System (INIS)

Zhou Yanmin; Sun Zhongning; Gu Haifeng; Wang Junlong

2014-01-01

With the deionized water as the absorbent, the solubility characteristics of the gaseous methyl iodide were studied under different temperature and pressure conditions, using a dynamic measuring method. The results show that within the range of experiment parameters, namely temperature is below 80℃ and pressure is lower than 0.3 MPa, the physical dissolution process of gaseous methyl iodide in water obeys Henry's law. The solubility coefficient under different temperature and pressure conditions was calculated based on the measurement results. Further research indicates that at atmospheric pressure, the solubility coefficient of methyl iodide in water decreases exponentially with the increase of temperature. While the pressure changes from 0.1 MPa to 0.3 MPa with equal interval, the solubility coefficient also increases linearly. The variation of the solubility coefficient with temperature under different pressure conditions all decreases exponentially. An equation is given to calculate the solubility coefficient of methyl iodide under different pressure and temperature conditions. (authors)

Uranium solubility and speciation in ground water

International Nuclear Information System (INIS)

Ollila, K.

1985-04-01

The purpose of this study has been to assess the solubility and possible species of uranium in groundwater at the disposal conditions of spent fuel. The effects of radiolysis and bentonite are considered. The assessment is based on the theoretical calculations found in the literature. The Finnish experimental results are included. The conservative estimate for uranium solubility under the oxidizing conditions caused by alpha radiolysis is based on the oxidation of uranium to the U(VI) state and formation of carbonate complex. For the groundwater with the typical carbonate content of 275 mg/l and the high carbonate content of 485 mg/l due to bentonite, the solubility values of 360 mg u/l and 950 mg U/l, are obtained, respectively. The experimental results predict considerably lower values, 0.5-20 mg U/l. The solubility of uranium under the undisturbed reducing conditions may be calculated based on the hydrolysis, carbonate complexation and redox reactions. The results vary considerably depending on the thermodynamic data used. The wide ranges of the most important groundwater parameters are seen in the solubility values. The experimental results show the same trends. As a conservative value for the solubility in reducing groundwater 50-500 μg U/l is estimated. (author)

Exploiting the biosynthetic machinery of Streptomyces pilosus to engineer a water-soluble zirconium(iv) chelator.

Science.gov (United States)

Richardson-Sanchez, Tomas; Tieu, William; Gotsbacher, Michael P; Telfer, Thomas J; Codd, Rachel

2017-07-21

The water solubility of a natural product-inspired octadentate hydroxamic acid chelator designed to coordinate Zr(iv)-89 has been improved by using a combined microbiological-chemical approach to engineer four ether oxygen atoms into the main-chain region of a methylene-containing analogue. First, an analogue of the trimeric hydroxamic acid desferrioxamine B (DFOB) that contained three main-chain ether oxygen atoms (DFOB-O 3 ) was generated from cultures of the native DFOB-producer Streptomyces pilosus supplemented with oxybis(ethanamine) (OBEA), which competed against the native 1,5-diaminopentane (DP) substrate during DFOB assembly. This precursor-directed biosynthesis (PDB) approach generated a suite of DFOB analogues containing one (DFOB-O 1 ), two (DFOB-O 2 ) or three (DFOB-O 3 ) ether oxygen atoms, with the latter produced as the major species. Log P measurements showed DFOB-O 3 was about 45 times more water soluble than DFOB. Second, a peptide coupling chain-extension reaction between DFOB-O 3 and the synthetic ether-containing endo-hydroxamic acid monomer 4-((2-(2-aminoethoxy)ethyl)(hydroxy)amino)-4-oxobutanoic acid (PBH-O 1 ) gave the water soluble tetrameric hydroxamic acid DFOB-O 3 -PBH-O 1 as an isostere of sparingly water soluble DFOB-PBH. The complex between DFOB-O 3 -PBH-O 1 and nat Zr(iv), examined as a surrogate measure of the radiolabelling procedure, analysed by LC-MS as the protonated adduct ([M + H] + , m/z obs = 855.2; m/z calc = 855.3), with supporting HRMS data. The use of a microbiological system to generate a water-soluble analogue of a natural product for downstream semi-synthetic chemistry is an attractive pathway for developing new drugs and imaging agents. The improved water solubility of DFOB-O 3 -PBH-O 1 could facilitate the synthesis and purification of downstream products, as part of the ongoing development of ligands optimised for Zr(iv)-89 immunological PET imaging.

Antimicrobial and Antifungal Effects of Acid and Water-Soluble Chitosan Extracted from Indian Shrimp (Fenneropenaeus indicus Shell

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Ali Taheri

2013-06-01

Full Text Available Background & Objective : Currently, efforts are underway to seek new and effective antimicrobial agents, and marine resources are potent candidates for this aim. The following study was conducted to investigate the efficacy of water-soluble and acid-soluble chitosan against some pathogenic organisms.   Materials & Method s: Inhibition zone of different concentrations (5, 7.5, and 10 mg/ml of acid- soluble and water-soluble chitosan were examined for in vitro antibacterial activity against 4 kinds of hospital bacteria and penicillium sp. Results were compared with 4 standard antibiotics: streptomycin, gentamicin, tetracycline, and erythromycin. Furthermore, minimum inhibitory concentration and minimum lethal concentration were determined.   Results: Inhibition activity of acid-soluble chitosan (10% showed the best result (p value < 0.05, whereas water-soluble chitosan exhibited the least antibacterial effects (p value < 0.05. Chitosan demonstrated maximum effect on V. cholera cerotype ogava , and the least effect was seen on E. coli (p value < 0.05. Acid-soluble chitosan had a more potent effect than the standard antibiotics. Also, acid-soluble chitosan (10% and water-soluble chitosan showed maximum inhibitory effects on penicillium sp.   Conclusion: Chitosan showed maximum antibacterial effect against S. aureus, V. cholerae cerotype ogava, and water-soluble chitosan demonstrated good antifungal effects, revealing a statistically significant difference with common antibacterial and antifungal medicines.

Influence of the Relative Enamel Abrasivity (REA) of Toothpastes on the Uptake of KOH-soluble and Structurally Bound Fluoride.

Science.gov (United States)

Elmazi, Valbona; Sener, Beatrice; Attin, Thomas; Imfeld, Thomas; Wegehaupt, Florian J

2015-01-01

To determine the influence of the relative enamel abrasivity (REA) of fluoridated toothpaste on the uptake of KOH-soluble and structurally bound fluoride into enamel. Bovine enamel samples were randomly allocated to 6 groups (n=36 per group). Groups A to C were treated with sodium fluoride (NaF) toothpastes and groups D to F with amine fluoride (AmF) toothpastes (1500 ppm F each). The REA in groups A and D was 2, in groups B and E it was 6 and in groups C and F it was 9. Twice a day, 18 samples of each group were immersed for 2 min in a slurry (toothpaste:artificial saliva=1:3), while the remaining samples were brushed with the respective slurry (2.5 N force; 60 strokes/min; 2 min). All samples were stored at 37°C and 100% humidity. After five days, the amount of KOH-soluble and structurally bound fluoride was determined and statistically compared by Scheffe's post-hoc tests. REA value and mode of application (immersion or brushing) had no significant influence on the amount of either kind of fluoride from NaF toothpastes. Only for the NaF toothpaste with REA 6 was the amount of KOH-soluble fluoride significantly higher after brushing. With AmF toothpastes, KOH-soluble and structurally bound fluoride concentrations were significantly higher when the samples were brushed. Furthermore, in the REA-2 group, the amounts of KOH-soluble fluoride (brushed or immersed) and structurally bound fluoride (brushed) were significantly higher than in the other groups. The REA dependency of KOH-soluble and structurally bound fluoride was found only for the AmF toothpastes. Using AmF toothpaste, the mode of application influenced the uptake of KOH-soluble and structurally bound fluoride into enamel.

Evaluation of ammonium nitrate phosphate (Suphala) having different water soluble phosphorus levels on black soils

International Nuclear Information System (INIS)

Deo Dutt; Mutatkar, V.K.; Chapke, V.G.

1974-01-01

Efficiency of the laboratory prepared 32 P tagged ammonium nitrate phosphate (Suphala) varying in water soluble P was studied both on calcareous and non-calcareous soils of Maharashtra for bajra and wheat crops under greenhouse conditions. The results revealed a significant increase in dry matter production and uptake of total and fertilizer P with Suphala containing 30-32% water-soluble phosphorus. (author)

Dry season aerosol iron solubility in tropical northern Australia

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V. H. L. Winton

2016-10-01

Full Text Available Marine nitrogen fixation is co-limited by the supply of iron (Fe and phosphorus in large regions of the global ocean. The deposition of soluble aerosol Fe can initiate nitrogen fixation and trigger toxic algal blooms in nitrate-poor tropical waters. We present dry season soluble Fe data from the Savannah Fires in the Early Dry Season (SAFIRED campaign in northern Australia that reflects coincident dust and biomass burning sources of soluble aerosol Fe. The mean soluble and total aerosol Fe concentrations were 40 and 500 ng m−3 respectively. Our results show that while biomass burning species may not be a direct source of soluble Fe, biomass burning may substantially enhance the solubility of mineral dust. We observed fractional Fe solubility up to 12 % in mixed aerosols. Thus, Fe in dust may be more soluble in the tropics compared to higher latitudes due to higher concentrations of biomass-burning-derived reactive organic species in the atmosphere. In addition, biomass-burning-derived particles can act as a surface for aerosol Fe to bind during atmospheric transport and subsequently be released to the ocean upon deposition. As the aerosol loading is dominated by biomass burning emissions over the tropical waters in the dry season, additions of biomass-burning-derived soluble Fe could have harmful consequences for initiating nitrogen-fixing toxic algal blooms. Future research is required to quantify biomass-burning-derived particle sources of soluble Fe over tropical waters.

Comparison of water sorption and solubility of Acropars and Meliodent heat cure acrylic resins

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Golbidi F

2006-06-01

Full Text Available Background and Aim: Water sorption and solubility are important properties of acrylic resins. Denture base acrylic resins have low solubility. This solubility results from the leaching out of unreacted monomer and water soluble additives into the oral fluids. The solubility of denture bases can cause oral soft tissue reactions. In addition, water absorbed into this material acts as a plasticizer and decreases the mechanical properties such as hardness, transverse strength, fatigue limit and also can change the color and dimensional stability. The aim of this study was to compare the water sorption and solubility of Acropars and Meliodent heat cure acrylic resins. Materials and Methods: This experimental study was performed on the basis of ADA specification No.12 and ISO No.1567 and standards NO: 2571 of Institute of Standards & Industrial Research of Iran. Six disc form samples of each acrylic resin were prepared, with the dimension of 50×0.5 mm. After desiccating, the samples were kept in an oven for 24 hours and weighed. Then they were immersed in water, kept in oven for 7 days and weighed again. After this phase, the samples were carried to a dessicator, for 24 hours and kept in an oven for drying and were weighed for the third time. Data were analyzed with Mann Whitney and one sample t-test. P<0.05 was considered as the limit of significance. Results: Water sorption mean values were 30.5±0.1 µg/mm3 or 0.76±0.01 mg/cm2 for Meliodent samples and 30.7±0.87 µg/mm3 or 0.77±0.009 mg/cm2 for Acropars samples. No significant difference was observed in water sorption of these two materials (P=0.9. Meliodent acrylic resin showed lower solubility (1.7±0.097 µg/mm3 or 0.042±0.001 mg/cm2 than Acropars acrylic resin (2.5±0.13 µg/mm3 or 0.062±0.001 mg/cm2 (P=0.002. Conclusion: Acropars heat cure acrylic resin matched well with the requirements of the international standards for water sorption, but its solubility was not favorable. This problem

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects.

Science.gov (United States)

Hagen, Imke; Schulte, Dominik M; Müller, Nike; Martinsen, Jessica; Türk, Kathrin; Hedderich, Jürgen; Schreiber, Stefan; Laudes, Matthias

2015-06-01

Obesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). 22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m(2)) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). Mean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=-0.642, p=0.001) and HOMA (rS=-0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=-0.650, p=0.022) during intervention. Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of an abiraterone acetate formulation with improved oral bioavailability guided by absorption modeling based on in vitro dissolution and permeability measurements.

Science.gov (United States)

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Semsey, Sándor; Molnár, László; Ránky, Soma; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-30

Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability. Abiraterone acetate is poorly water soluble which is believed to be responsible for its very low bioavailability in the fasted state and its significant positive food effect. In this work, we have successfully used in vitro dissolution, solubility and permeability measurements in biorelevant media to describe the dissolution characteristics of different abiraterone acetate formulations. Mathematical modeling of fraction dose absorbed indicated that reducing the particle size of the drug cannot be expected to result in significant improvement in bioavailability in the fasted state. In the fed state, the same formulation approach can result in a nearly complete absorption of the dose; thereby, further increasing the food effect. Using a "bottom-up" formulation method we improved both the dissolution rate and the apparent solubility of the compound. In beagle dog studies, this resulted in a ≫>10-fold increase in bioavailability in the fasted state when compared to the marketed drug and the elimination of the food effect. Calculated values of fraction dose absorbed were in agreement with the observed relative bioavailability values in beagle dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

Encapsulation of β-carotene within ferritin nanocages greatly increases its water-solubility and thermal stability.

Science.gov (United States)

Chen, Lingli; Bai, Guangling; Yang, Rui; Zang, Jiachen; Zhou, Ting; Zhao, Guanghua

2014-04-15

Carotenoids may play a number of potential health benefits for human. However, their use in food industry is limited mostly because of their poor water-solubility and low thermal stability. Ferritins are widely distributed in nature with a shell-like structure which offers a great opportunity to improve the water-solubility and thermal stability of the carotenoids by encapsulation. In this work, recombinant human H-chain ferritin (rHuHF) was prepared and used to encapsulate β-carotene, a typical compound among carotenoids, by taking advantage of the reversible dissociation and reassembly characteristic of apoferritin in different pH environments. Results from high-performance liquid chromatography (HPLC), UV/Vis spectroscopy and transmission electron microscope (TEM) indicated that β-carotene molecules were successfully encapsulated within protein cages with a β-carotene/protein molar ratio of 12.4-1. Upon such encapsulation, these β-carotene-containing apoferritin nanocomposites were water-soluble. Interestingly, the thermal stability of the β-carotene encapsulated within apoferritin nanocages was markedly improved as compared to free β-carotene. These new properties might be favourable to the utilisation of β-carotene in food industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of gamma irradiation on the change of solubility and anti-inflammation activity of chrysin in macrophage cells and LPS-injected endotoxemic mice

International Nuclear Information System (INIS)

Byun, Eui-Baek; Jang, Beom-Su; Byun, Eui-Hong; Sung, Nak-Yun

2016-01-01

This study evaluated the changes of solubility and anti-inflammatory properties of structurally modified gamma-irradiated chrysin. Chrysin was irradiated at various doses for a physical analysis and determining any structural changes and solubility. As shown through the physical analysis, the main peak of the chrysin was decreased as the irradiation dose increased, and it was concomitant with the appearance of several new peaks, which were highly increased in 50 kGy gamma-irradiated chrysin. The solubility was markedly increased in the gamma-irradiated groups. As shown through a physiological analysis, both gamma-irradiated- (15–50 kGy) and intact-chrysin (0 kGy) did not exert cytotoxicity to bone-marrow derived macrophages. The treatment of LPS-stimulated macrophages with 50 kGy gamma-irradiated chrysin resulted in a dose-dependent decrease in pro-inflammatory mediators, such as iNOS-mediated NO, PGE 2 , COX-2, and cell surface marker (CD80 and CD86), as well as pro-inflammatory cytokines (TNF-α and IL-6), when compared to the intact-chrysin treated group. Mechanically, we found that the inhibition of these pro-inflammatory mediators induced by gamma-irradiated chrysin occurred through an inhibition of MAPKs (ERK1/2 and p38) and the NF-κB signaling pathways. Furthermore, the anti-inflammatory activity remained in the LPS-injected animal model. In this model, gamma-irradiated chrysin treatment highly increased the mouse survival, and significantly decreased the serum cytokine (TNF-α, IL-6 and IL-1β) levels. From these findings, the anti-inflammatory action by gamma-irradiated chrysin may be closely mediated with structural modification. It seems likely that gamma irradiation can be an effective tool for improvement of the physical and physiological properties of polyphenols. - Highlights: • Gamma irradiation leads to the structural modification of chrysin. • Gamma irradiation improved the solubility of chrysin. • Gamma-irradiated chrysin significantly

Daily rhythm of circulating fat soluble vitamin concentration (A, D, E and K in the horse

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Caola Giovanni

2004-07-01

Full Text Available Abstract Background Many physiological processes of mammalian species exhibit daily rhythmicity. An intrinsic relationship exists between fat soluble vitamins (A, D, E and K and several body functions. Few investigations on the rhythmic pattern of vitamins in domestic animals have been carried out. The present study evaluated the circadian rhythmicity of fat soluble vitamins in the horse. Methods Blood samples from 5 Thoroughbred mares were collected at four-hour intervals over a 48-hour period (starting at 8:00 hours on day 1 and finishing at 4:00 on day 2 via an intravenous cannula inserted into the jugular vein. Fat soluble vitamin concentration in the serum (A, D, E and K was measured by HPLC. One-way repeated measures analysis of variance (ANOVA was used to determine significant differences. p values Results ANOVA showed a highly significant effect of time in all the horses for the vitamins studied (p Conclusion Fat soluble vitamins exhibit daily rhythmicity with diurnal peak. Further investigations could help optimize the use of these substances according to their circadian (or other rhythms.

Soluble and cell wall-bound phenolic acids and ferulic acid dehydrodimers in rye flour and five bread model systems: insight into mechanisms of improved availability.

Science.gov (United States)

Dynkowska, Wioletta M; Cyran, Malgorzata R; Ceglińska, Alicja

2015-03-30

The bread-making process influences bread components, including phenolics that significantly contribute to its antioxidant properties. Five bread model systems made from different rye cultivars were investigated to compare their impact on concentration of ethanol-soluble (free and ester-bound) and insoluble phenolics. Breads produced by a straight dough method without acid addition (A) and three-stage sourdough method with 12 h native starter preparation (C) exhibited the highest, genotype-dependent concentrations of free phenolic acids. Dough acidification by direct acid addition (method B) or by gradual production during prolonged starter fermentation (24 and 48 h, for methods D and E) considerably decreased their level. However, breads B were enriched in soluble ester-bound fraction. Both direct methods, despite substantial differences in dough pH, caused a similar increase in the amount of insoluble ester-bound fraction. The contents of phenolic fractions in rye bread were positively related to activity level of feruloyl esterase and negatively to those of arabinoxylan-hydrolysing enzymes in wholemeal flour. The solubility of rye bread phenolics may be enhanced by application of a suitable bread-making procedure with respect to rye cultivar, as the mechanisms of this process are also governed by a response of an individual genotype with specific biochemical profile. © 2014 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Characterization of Soluble Organics in Produced Water

Energy Technology Data Exchange (ETDEWEB)

Bostick, D.T.

2002-01-16

-selective electrodes and inductively coupled plasma (ICP)-atomic emission spectrometry (AES). The WSO found in produced water samples was primarily polar in nature and distributed between the low and midrange carbon ranges. Typical levels of total extractable material (TEM) was about 20 mg/L; that associated with the aromatic fraction was present at 0.2 mg/L and that in the saturated hydrocarbon fraction was present at less than 0.02 mg/L. Formic, acetic, and propionic acids were also found in the produced water, occurring at a total concentration of 30 mg/L. It was estimated that the presence of 30 mg/L organic acids would artificially overstate TEM content by 2 mg/L. Of the five tested parameters, the factor that most controlled the total WSO in produced water was that of aqueous phase pH. Beyond a value of pH7 significant quantities of C{sub 10}-C{sub 20} range material become markedly soluble as they deprotonate in a basic aqueous phase. Both the absolute and relative volumes of GOM brine and crude additionally affected total WSO. Produced water appeared to reach a saturation level of WSO at a.50% water/oil ratio. Pressure slightly enhanced WSO by increasing the relative quantity of C{sub 6}-C{sub 10} range material. Temperature primarily altered the relative ratio of carbon ranges within the WSO without significantly elevating the total WSO in the GOM brine. Salinity had the least affect on the chemical character or the carbon size of WSO in produced water.

Solubility of pllutonium in alkaline salt solutions

International Nuclear Information System (INIS)

Hobbs, D.T.; Edwards, T.B.

1993-01-01

Plutonium solubility data from several studies have been evaluated. For each data set, a predictive model has been developed where appropriate. In addition, a statistical model and corresponding prediction intervals for plutonium solubility as a quadratic function of the hydroxide concentration have been developed. Because of the wide range of solution compositions, the solubility of plutonium can vary by as much as three orders of magnitude for any given hydroxide concentration and still remain within the prediction interval. Any nuclear safety assessments that depend on the maximum amount of plutonium dissolved in alkaline salt solutions should use concentrations at least as great as the upper prediction limits developed in this study. To increase the confidence in the prediction model, it is recommended that additional solubility tests be conducted at low hydroxide concentrations and with all of the other solution components involved. To validate the model for application to actual waste solutions, it is recommended that the plutonium solubilities in actual waste solutions be determined and compared to the values predicted by the quadratic model

Core-shell nanofibers of curcumin/cyclodextrin inclusion complex and polylactic acid: Enhanced water solubility and slow release of curcumin.

Science.gov (United States)

Aytac, Zeynep; Uyar, Tamer

2017-02-25

Core-shell nanofibers were designed via electrospinning using inclusion complex (IC) of model hydrophobic drug (curcumin, CUR) with cyclodextrin (CD) in the core and polymer (polylactic acid, PLA) in the shell (cCUR/HPβCD-IC-sPLA-NF). CD-IC of CUR and HPβCD was formed at 1:2 molar ratio. The successful formation of core-shell nanofibers was revealed by TEM and CLSM images. cCUR/HPβCD-IC-sPLA-NF released CUR slowly but much more in total than PLA-CUR-NF at pH 1 and pH 7.4 due to the restriction of CUR in the core of nanofibers and solubility improvement shown in phase solubility diagram, respectively. Improved antioxidant activity of cCUR/HPβCD-IC-sPLA-NF in methanol:water (1:1) is related with the solubility enhancement achieved in water based system. The slow reaction of cCUR/HPβCD-IC-sPLA-NF in methanol is associated with the shell inhibiting the quick release of CUR. On the other hand, cCUR/HPβCD-IC-sPLA-NF exhibited slightly higher rate of antioxidant activity than PLA-CUR-NF in methanol:water (1:1) owing to the enhanced solubility. To conclude, slow release of CUR was achieved by core-shell nanofiber structure and inclusion complexation of CUR with HPβCD provides high solubility. Briefly, electrospinning of core-shell nanofibers with CD-IC core could offer slow release of drugs as well as solubility enhancement for hydrophobic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing the solubility and bioavailability of poorly water-soluble drugs using supercritical antisolvent (SAS) process.

Science.gov (United States)

Abuzar, Sharif Md; Hyun, Sang-Min; Kim, Jun-Hee; Park, Hee Jun; Kim, Min-Soo; Park, Jeong-Sook; Hwang, Sung-Joo

2018-03-01

Poor water solubility and poor bioavailability are problems with many pharmaceuticals. Increasing surface area by micronization is an effective strategy to overcome these problems, but conventional techniques often utilize solvents and harsh processing, which restricts their use. Newer, green technologies, such as supercritical fluid (SCF)-assisted particle formation, can produce solvent-free products under relatively mild conditions, offering many advantages over conventional methods. The antisolvent properties of the SCFs used for microparticle and nanoparticle formation have generated great interest in recent years, because the kinetics of the precipitation process and morphologies of the particles can be accurately controlled. The characteristics of the supercritical antisolvent (SAS) technique make it an ideal tool for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review article focuses on SCFs and their properties, as well as the fundamentals of overcoming poorly water-soluble drug properties by micronization, crystal morphology control, and formation of composite solid dispersion nanoparticles with polymers and/or surfactants. This article also presents an overview of the main aspects of the SAS-assisted particle precipitation process, its mechanism, and parameters, as well as our own experiences, recent advances, and trends in development. Copyright © 2017 Elsevier B.V. All rights reserved.

Intestinal absorption of water-soluble vitamins in health and disease.

Science.gov (United States)

Said, Hamid M

2011-08-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current

Fabrication and Optimization of Self-Microemulsions to Improve the Oral Bioavailability of Total Flavones of Hippophaë rhamnoides L.

Science.gov (United States)

Guo, Ruixue; Guo, Xinbo; Hu, Xiaodan; Abbasi, Arshad Mehmood; Zhou, Lin; Li, Tong; Fu, Xiong; Liu, Rui Hai

2017-12-01

The purpose of this work was to improve the oral bioavailability of a poorly soluble functional food ingredient, the total flavones of Hippophaë rhamnoides L. (TFH). A self-microemulsion drug delivery system (SMEDDS) was developed to overcome the problems of poor absorption of TFH in vivo. The optimal SMEDDS significantly enhanced the solubility of TFH up to 530 times compared to that in water. The mean droplet size was 61.76 nm with uniform distribution. And the loaded system was stable at 25 °C for 3 mo with transparent appearance. The in vitro release of TFH from SMEDDS was faster and more complete than that from suspension. After oral administration of TFH-SMEDDS in rats, the relative bioavailability of TFH was dramatically improved for 3.09 times compared with the unencapsulated form. The investigation indicated the potential application of SMEDDS as a vehicle to improve the oral bioavailability of TFH. The lipid-based nanotechnology, namely self-microemulsion drug delivery system (SMEDDS) was used to improve the bioavailability and oral delivery of total flavones of Hippophaë rhamnoides L. (TFH). The relevant bioavailability of TFH could be remarkably 3-fold improved by the optimized SMEDDS. The SMEDDS produced via a simple one-step process for poorly soluble TFH to achieve a significant improvement in the bioavailability, may endorse the promising utilization of TFH in functional foods as well as pharmaceutical fields with an enhanced absorption in vivo. © 2017 Institute of Food Technologists®.

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

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Abisambra Jose F

2010-11-01

Full Text Available Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB, the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17: Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.

Application of transglycosylated stevia and hesperidin as drug carriers to enhance biopharmaceutical properties of poorly-soluble artemisinin.

Science.gov (United States)

Letchmanan, Kumaran; Shen, Shou-Cang; Ng, Wai Kiong; Tan, Reginald B H

2018-01-01

Biopharmaceutical properties of poorly water-soluble antimalarial drug, Artemisinin (ART), were improved by formulating amorphous solid dispersions with transglycosylated food additives (Hsp-G and Stevia-G) via co-spray drying. Both the formulated ART/Hsp-G and ART/Stevia-G showed superior dissolution properties with a burst release of more than 95% of drug within 5 min, whereas untreated ART dissolved only 4% in 5min. The supersaturation solubility of the formulated ART was enhanced by 2-fold as compared with untreated counterpart. The storage stability tests indicated that these formulations chemically stable at room temperature and under low humidity (water-soluble ART. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and In Vitro Evaluation of a New Nano-Microparticulate System for Enhanced Aqueous-Phase Solubility of Curcumin

OpenAIRE

Guzman-Villanueva, Diana; El-Sherbiny, Ibrahim M.; Herrera-Ruiz, Dea; Smyth, Hugh D. C.

2013-01-01

Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-mi...

pH-metric solubility. 2: correlation between the acid-base titration and the saturation shake-flask solubility-pH methods.

Science.gov (United States)

Avdeef, A; Berger, C M; Brownell, C

2000-01-01

The objective of this study was to compare the results of a normal saturation shake-flask method to a new potentiometric acid-base titration method for determining the intrinsic solubility and the solubility-pH profiles of ionizable molecules, and to report the solubility constants determined by the latter technique. The solubility-pH profiles of twelve generic drugs (atenolol, diclofenac.Na, famotidine, flurbiprofen, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, labetolol.HCl, naproxen, phenytoin, and propranolol.HCl), with solubilities spanning over six orders of magnitude, were determined both by the new pH-metric method and by a traditional approach (24 hr shaking of saturated solutions, followed by filtration, then HPLC assaying with UV detection). The 212 separate saturation shake-flask solubility measurements and those derived from 65 potentiometric titrations agreed well. The analysis produced the correlation equation: log(1/S)titration = -0.063(+/- 0.032) + 1.025(+/- 0.011) log(1/S)shake-flask, s = 0.20, r2 = 0.978. The potentiometrically-derived intrinsic solubilities of the drugs were: atenolol 13.5 mg/mL, diclofenac.Na 0.82 microg/mL, famotidine 1.1 mg/ mL, flurbiprofen 10.6 microg/mL, furosemide 5.9 microg/mL, hydrochlorothiazide 0.70 mg/mL, ibuprofen 49 microg/mL, ketoprofen 118 microg/mL, labetolol.HCl 128 microg/mL, naproxen 14 microg/mL, phenytoin 19 microg/mL, and propranolol.HCl 70 microg/mL. The new potentiometric method was shown to be reliable for determining the solubility-pH profiles of uncharged ionizable drug substances. Its speed compared to conventional equilibrium measurements, its sound theoretical basis, its ability to generate the full solubility-pH profile from a single titration, and its dynamic range (currently estimated to be seven orders of magnitude) make the new pH-metric method an attractive addition to traditional approaches used by preformulation and development scientists. It may be useful even to discovery

Polymer brush hexadecyltrimethylammonium bromide (CTAB) modified poly (propylene-g-styrene sulphonic acid) fiber (ZB-1): CTAB/ZB-1 as a promising strategy for improving the dissolution and physical stability of poorly water-soluble drugs.

Science.gov (United States)

Cao, Jinxu; Yang, Baixue; Wang, Yumei; Wei, Chen; Wang, Hongyu; Li, Sanming

2017-11-01

The feasibility of polymer brush as drug delivery vehicle was demonstrated with the goal of improving the dissolution and physical stability of poorly water-soluble drugs. Polymer brush CTAB/ZB-1 was synthesized by electrostatic interaction using a physical modification method with anionic poly (propylene-g-styrene sulphonic acid) fiber (ZB-1) as the substrate and cationic hexadecyltrimethylammonium bromide (CTAB) as the modifier. The polymer brush structure of CTAB/ZB-1 was validated by atomic force microscopy (AFM) and the channels of brush provided the drug loading sites. Flurbiprofen (FP), a BCS class II representative drug, was selected as the model poorly water-soluble drug to be loaded into this polymer brush. Then the drug loading and release were systematically investigated. Besides, the transformation from crystalline FP to amorphous state was observed by differential scanning calorimeter (DSC). In vitro dissolution in pure water and pH1.2 HCl media with/without 0.1% sodium dodecyl sulfate (SDS) was tested. Moreover, the optimal formulations (namely carrier/drug ratios) were determined. The results demonstrated prominent improvement of dissolution when FP was released from CTAB/ZB-1. After a long time storage, FP remained amorphous in CTAB/ZB-1 according to DSC determinations and performed an approximately equivalent dissolution compared with fresh samples, suggesting the advantage of CTAB/ZB-1 as carrier in enhancing the physical stability of drugs. The study introduced the versatile easily formulated polymer brush CTAB/ZB-1 and demonstrated the potential of polymer brush as an alternative approach for improving the dissolution and physical stability of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Inter-species comparative analysis of components of soluble sugar concentration in fleshy fruits

Directory of Open Access Journals (Sweden)

Zhanwu eDai

2016-05-01

conserved among the three fruit species. These distinct modes appear to be quite species-specific, but the intensity of the effect may significantly vary depending on the genotype and management practices. These results provide novel insights into the drivers of differences in soluble sugar concentration among fleshy fruits.

Use Of Stream Analyzer For Solubility Predictions Of Selected Hanford Tank Waste

International Nuclear Information System (INIS)

Pierson, Kayla; Belsher, Jeremy; Ho, Quynh-dao

2012-01-01

The Hanford Tank Waste Operations Simulator (HTWOS) models the mission to manage, retrieve, treat and vitrify Hanford waste for long-term storage and disposal. HTWOS is a dynamic, flowsheet, mass balance model of waste retrieval and treatment activities. It is used to evaluate the impact of changes on long-term mission planning. The project is to create and evaluate the integrated solubility model (ISM). The ISM is a first step in improving the chemistry basis in HTWOS. On principal the ISM is better than the current HTWOS solubility. ISM solids predictions match the experimental data well, with a few exceptions. ISM predictions are consistent with Stream Analyzer predictions except for chromium. HTWOS is producing more realistic results with the ISM

Temperature and sodium chloride effects on the solubility of anthracene in water

International Nuclear Information System (INIS)

Arias-Gonzalez, Israel; Reza, Joel; Trejo, Arturo

2010-01-01

The solubility of anthracene was measured in pure water and in sodium chloride aqueous solution (salt concentration, m/mol . kg -1 = 0.1006, 0.5056, and 0.6082) at temperatures between (278 and 333) K. Solubility of anthracene in pure water agrees fairly well with values reported in earlier similar studies. Solubility of anthracene in sodium chloride aqueous solutions ranged from (6 . 10 -8 to 143 . 10 -8 ) mol . kg -1 . Sodium chloride had a salting-out effect on the solubility of anthracene. The salting-out coefficients did not vary significantly with temperature over the range studied. The average salting-out coefficient for anthracene was 0.256 kg . mol -1 . The standard molar Gibbs free energies, Δ tr G o , enthalpies, Δ tr H o , and entropies, Δ tr S o , for the transfer of anthracene from pure water to sodium chloride aqueous solutions were also estimated. Most of the estimated Δ tr G o values were positive [(20 to 1230) J . mol -1 ]. The analysis of the thermodynamic parameters shows that the transfer of anthracene from pure water to sodium chloride aqueous solution is thermodynamically unfavorable, and that this unfavorable condition is caused by a decrease in entropy.

Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

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Avital Beig

2016-10-01

Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

Water Soluble Polymers for Pharmaceutical Applications

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Veeran Gowda Kadajji

2011-11-01

Full Text Available Advances in polymer science have led to the development of novel drug delivery systems. Some polymers are obtained from natural resources and then chemically modified for various applications, while others are chemically synthesized and used. A large number of natural and synthetic polymers are available. In the present paper, only water soluble polymers are described. They have been explained in two categories (1 synthetic and (2 natural. Drug polymer conjugates, block copolymers, hydrogels and other water soluble drug polymer complexes have also been explained. The general properties and applications of different water soluble polymers in the formulation of different dosage forms, novel delivery systems and biomedical applications will be discussed.

Solubility of actinides and surrogates in nuclear glasses

International Nuclear Information System (INIS)

Lopez, Ch.

2003-01-01

The nuclear wastes are currently incorporated in borosilicate glass matrices. The resulting glass must be perfectly homogeneous. The work discussed here is a study of actinide (thorium and plutonium) solubility in borosilicate glass, undertaken to assess the extent of actinide solubility in the glass and to understand the mechanisms controlling actinide solubilization. Glass specimens containing; actinide surrogates were used to prepare and optimize the fabrication of radioactive glass samples. These preliminary studies revealed that actinide Surrogates solubility in the glass was enhanced by controlling the processing temperature, the dissolution kinetic of the surrogate precursors, the glass composition and the oxidizing versus reducing conditions. The actinide solubility was investigated in the borosilicate glass. The evolution of thorium solubility in borosilicate glass was determined for temperatures ranging from 1200 deg C to 1400 deg C.Borosilicate glass specimens containing plutonium were fabricated. The experimental result showed that the plutonium solubility limit ranged from 1 to 2.5 wt% PuO 2 at 1200 deg C. A structural approach based on the determination of the local structure around actinides and their surrogates by EXAFS spectroscopy was used to determine their structural role in the glass and the nature of their bonding with the vitreous network. This approach revealed a correlation between the length of these bonds and the solubility of the actinides and their surrogates. (author)

Serum Level of a Soluble Form of Endoglin (CD105 is Decreased after Goeckerman’s Therapy of Psoriasis

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David Pohl

2011-01-01

Full Text Available Background. Goeckerman’s therapy (GT of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. The aim of study was to evaluate the influence of GT of psoriasis on proinflammatory and angiogenic activities expressed as changes in levels of endoglin (CD105. Methods. Serum levels of a soluble form of endoglin were measured in peripheral blood samples of 38 patients with psoriasis before and after therapy. Sixty three otherwise healthy blood donors serve as a control group. The efficacy of GT was expressed as changes in Psoriasis Area and Severity Index (PASI. Results. PASI score was significantly diminished by GT (p<0.001. Serum levels of soluble CD105 were significantly diminished after GT. The serum level of soluble CD105 dropped from 7.85 ± 2.26 ng/ml before therapy to 7.01 ± 1.71 ng/ml after therapy (p= 0.0002. Compared to serum levels of soluble CD105 in healthy blood donors, serum levels of soluble CD105 in patients before GT were significantly higher (p<0.001 and remained elevated after therapy (p<0.001. Angiogenic activity expressed as serum endoglin is diminished in patients with psoriasis treated by GT.

Solubility limited radionuclide transport through geologic media

International Nuclear Information System (INIS)

Muraoka, Susumu; Iwamoto, Fumio; Pigford, T.H.

1980-11-01

Prior analyses for the migration of radionuclides neglect solubility limits of resolved radionuclide in geologic media. But actually some of the actinides may appear in chemical forms of very low solubility. In the present report we have proposed the migration model with no decay parents in which concentration of radionuclide is limited in concentration of solubility in ground water. In addition, the analytical solutions of the space-time-dependent concentration are presented in the case of step release, band release and exponential release. (author)

Molecular Thermodynamic Modeling of Mixed Solvent Solubility

DEFF Research Database (Denmark)

Ellegaard, Martin Dela; Abildskov, Jens; O’Connell, John P.

2010-01-01

A method based on statistical mechanical fluctuation solution theory for composition derivatives of activity coefficients is employed for estimating dilute solubilities of 11 solid pharmaceutical solutes in nearly 70 mixed aqueous and nonaqueous solvent systems. The solvent mixtures range from...... nearly ideal to strongly nonideal. The database covers a temperature range from 293 to 323 K. Comparisons with available data and other existing solubility methods show that the method successfully describes a variety of observed mixed solvent solubility behaviors using solute−solvent parameters from...

Solubility Products of M(II) - Carbonates

International Nuclear Information System (INIS)

Grauer, Rolf; Berner, Urs

1999-01-01

Many solubility data for M(II) carbonates commonly compiled in tables are contradictory and sometimes obviously wrong. The quality of such data has been evaluated based on the original publications and reliable solubility constants have been selected for the carbonates of Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb with the help of cross-comparisons. (author)

Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.

Science.gov (United States)

Lukyanov, Anatoly N; Torchilin, Vladimir P

2004-05-07

Polymeric micelles have a whole set of unique characteristics, which make them very promising drug carriers, in particular, for poorly soluble drugs. Our review article focuses on micelles prepared from conjugates of water-soluble polymers, such as polyethylene glycol (PEG) or polyvinyl pyrrolidone (PVP), with phospholipids or long-chain fatty acids. The preparation of micelles from certain polymer-lipid conjugates and the loading of these micelles with various poorly soluble anticancer agents are discussed. The data on the characterization of micellar preparations in terms of their morphology, stability, longevity in circulation, and ability to spontaneously accumulate in experimental tumors via the enhanced permeability and retention (EPR) effect are presented. The review also considers the preparation of targeted immunomicelles with specific antibodies attached to their surface. Available in vivo results on the efficiency of anticancer drugs incorporated into plain micelles and immunomicelles in animal models are also discussed.

Boron solubility in Fe-Cr-B cast irons

International Nuclear Information System (INIS)

Guo Changqing; Kelly, P.M.

2003-01-01

Boron solubility in the as-cast and solution treated martensite of Fe-Cr-B cast irons, containing approximately 1.35 wt.% of boron, 12 wt.% of chromium, as well as other alloying elements, has been investigated using conventional microanalysis. The significant microstructural variations after tempering at 750 deg. C for 0.5-4 h, compared with the original as-cast and solution treated microstructures, indicated that the matrix consisted of boron and carbon supersaturated solid solutions. The boron solubility detected by electron microprobe was between 0.185-0.515 wt.% for the as-cast martensite and 0.015-0.0589 wt.% for the solution treated martensite, much higher than the accepted value of 0.005 wt.% in pure iron. These remarkable increases are thought to be associated with some metallic alloying element addition, such as chromium, vanadium and molybdenum, which have atomic diameters larger than iron, and expand the iron lattice to sufficiently allow boron atoms to occupy the interstitial sites in iron lattice

Solubility of lithium deuteride in liquid lithium

International Nuclear Information System (INIS)

Veleckis, E.; Yonco, R.M.; Maroni, V.A.

1977-01-01

The solubility of LiD in liquid lithium between the eutectic and monotectic temperatures was measured using a direct sampling method. Solubilities were found to range from 0.0154 mol.% LiD at 199 0 C to 3.32 mol.% LiD at 498 0 C. The data were used in the derivation of an expression for the activity coefficient of LiD as a function of temperature and composition and an equation relating deuteride solubility and temperature, thus defining the liquidus curve. Similar equations were also derived for the Li-LiH system using the existing solubility data. Extrapolation of the liquidus curves yielded the eutectic concentrations (0.040 mol.% LiH and 0.035 mol.% LiD) and the freezing point depressions (0.23 0 C for Li-LiH and 0.20 0 C for Li-LiD) at the eutectic point. The results are compared with the literature data for hydrogen and deuterium. The implications of the relatively high solubility of hydrogen isotopes in lithium just above the melting point are discussed with respect to the cold trapping of tritium in fusion reactor blankets. (Auth.)

Stability and solubility improvement of Sompoi (Acacia concinna Linn. pod extract by topical microemulsion

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Worrapan Poomanee

2017-07-01

Full Text Available The aim of this study was to enhance the solubility and stability of Acacia concinna extract by loading in a microemulsion for topical application. Both physical appearance and biological activities of the extract-loaded microemulsion were determined in comparison with the extract solution. Pseudoternary phase diagrams of three oil types including tea seed oil, grape seed oil, and sesame oil, together with polysorbate 85 or the mixture of polysorbate 85 and sorbitan oleate as surfactants, and absolute ethanol as a co-surfactant were constructed to optimize the microemulsion area. The selected microemulsion was then characterized for droplet size, polydispersity index, and viscosity. Tea seed oil exhibited the highest microemulsion area in the phase diagram because it had the highest unsaturated fatty acid content. The microemulsion composed of tea seed oil (5%, polysorbate 85 (40%, ethanol (20%, and water (35% exhibited Newtonian flow behavior with the droplet size and polydispersity index of 68.03 ± 1.09 nm and 0.44 ± 0.04, respectively. After 4% w/w of the extract was incorporated into the microemulsion, larger droplets size was observed (239.77 ± 12.69 nm with a lower polydispersity index (0.37 ± 0.02. After storage in various conditions, both physical appearances and the stability of biological activity of the extract-loaded microemulsion were improved compared to the solution. Therefore, the A. concinna loaded microemulsion may be a promising carrier for further development into a topical formulation and clinical trials for pharmaceutical and cosmeceutical applications are also suggested.

Thorium oxalate solubility and morphology

International Nuclear Information System (INIS)

Monson, P.R. Jr.; Hall, R.

1981-10-01

Thorium was used as a stand-in for studying the solubility and precipitation of neptunium and plutonium oxalates. Thorium oxalate solubility was determined over a range of 0.001 to 10.0 in the concentration parameter [H 2 C 2 O 4 ]/[HNO 3 ] 2 . Morphology of thorium oxide made from the oxalate precipitates was characterized by scanning electron microscopy. The different morphologies found for oxalate-lean and oxalate-rich precipitations were in agreement with predictions based on precipitation theory

The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility

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Frank KJ

2012-11-01

Full Text Available Kerstin J Frank,1,3 Ulrich Westedt,2 Karin M Rosenblatt,2 Peter Hölig,2 Jörg Rosenberg,2 Markus Mägerlein,2 Gert Fricker,3 Martin Brandl11Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark; 2Abbott GmbH and Co. KG, Ludwigshafen, Germany; 3Department of Pharmaceutical Technology, University of Heidelberg, Heidelberg, GermanyAbstract: Amorphous solid dispersions (ASDs are a promising formulation approach for poorly soluble active pharmaceutical ingredients (APIs, because they ideally enhance both dissolution rate and solubility. However, the mechanism behind this is not understood in detail. In the present study, we investigated the supramolecular and the nano/microparticulate structures that emerge spontaneously upon dispersion of an ASD in aqueous medium and elucidated their influence on solubility. The ASD, prepared by hot melt extrusion, contained the poorly soluble ABT-102 (solubility in buffer, 0.05 µg/mL, a hydrophilic polymer, and three surfactants. The apparent solubility of ABT-102 from the ASD-formulation was enhanced up to 200 times in comparison to crystalline ABT-102. At the same time, the molecular solubility, as assessed by inverse equilibrium dialysis, was enhanced two times. Asymmetrical flow field-flow fractionation in combination with a multiangle light-scattering detector, an ultraviolet detector, and a refractometer enabled us to separate and identify the various supramolecular assemblies that were present in the aqueous dispersions of the API-free ASD (placebo and of binary/ternary blends of the ingredients. Thus, the supramolecular assemblies with a molar mass between 20,000 and 90,000 could be assigned to the polyvinylpyrrolidone/vinyl acetate 64, while two other kinds of assemblies were assigned to different surfactant assemblies (micelles. The amount of ABT-102 remaining associated with each of the assemblies upon fractionation was quantified offline with high

Polyelectrolyte microcapsules for sustained delivery of water-soluble drugs

Energy Technology Data Exchange (ETDEWEB)

Anandhakumar, S.; Debapriya, M. [Department of Materials Engineering, Indian Institute of Science, Bangalore, 560012 (India); Nagaraja, V. [Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012 (India); Raichur, Ashok M., E-mail: amr@materials.iisc.ernet.in [Department of Materials Engineering, Indian Institute of Science, Bangalore, 560012 (India)

2011-03-12

Polyelectrolyte capsules composed of weak polyelectrolytes are introduced as a simple and efficient system for spontaneous encapsulation of low molecular weight water-soluble drugs. Polyelectrolyte capsules were prepared by layer-by-layer (LbL) assembling of weak polyelectrolytes, poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) on polystyrene sulfonate (PSS) doped CaCO{sub 3} particles followed by core removal with ethylene-diaminetetraacetic acid (EDTA). The loading process was observed by confocal laser scanning microscopy (CLSM) using tetramethylrhodamineisothiocyanate labeled dextran (TRITC-dextran) as a fluorescent probe. The intensity of fluorescent probe inside the capsule decreased with increase in cross-linking time. Ciprofloxacin hydrochloride (a model water-soluble drug) was spontaneously deposited into PAH/PMA capsules and their morphological changes were investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The quantitative study of drug loading was also elucidated which showed that drug loading increased with initial drug concentration, but decreased with increase in pH. The loaded drug was released in a sustained manner for 6 h, which could be further extended by cross-linking the capsule wall. The released drug showed significant antibacterial activity against E. coli. These findings indicate that such capsules can be potential carriers for water-soluble drugs in sustained/controlled drug delivery applications.

Polyelectrolyte microcapsules for sustained delivery of water-soluble drugs

International Nuclear Information System (INIS)

Anandhakumar, S.; Debapriya, M.; Nagaraja, V.; Raichur, Ashok M.

2011-01-01

Polyelectrolyte capsules composed of weak polyelectrolytes are introduced as a simple and efficient system for spontaneous encapsulation of low molecular weight water-soluble drugs. Polyelectrolyte capsules were prepared by layer-by-layer (LbL) assembling of weak polyelectrolytes, poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) on polystyrene sulfonate (PSS) doped CaCO 3 particles followed by core removal with ethylene-diaminetetraacetic acid (EDTA). The loading process was observed by confocal laser scanning microscopy (CLSM) using tetramethylrhodamineisothiocyanate labeled dextran (TRITC-dextran) as a fluorescent probe. The intensity of fluorescent probe inside the capsule decreased with increase in cross-linking time. Ciprofloxacin hydrochloride (a model water-soluble drug) was spontaneously deposited into PAH/PMA capsules and their morphological changes were investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The quantitative study of drug loading was also elucidated which showed that drug loading increased with initial drug concentration, but decreased with increase in pH. The loaded drug was released in a sustained manner for 6 h, which could be further extended by cross-linking the capsule wall. The released drug showed significant antibacterial activity against E. coli. These findings indicate that such capsules can be potential carriers for water-soluble drugs in sustained/controlled drug delivery applications.

Effect of fasting on the urinary excretion of water-soluble vitamins in humans and rats.

Science.gov (United States)

Fukuwatari, Tsutomu; Yoshida, Erina; Takahashi, Kei; Shibata, Katsumi

2010-01-01

Recent studies showed that the urinary excretion of the water-soluble vitamins can be useful as a nutritional index. To determine how fasting affects urinary excretion of water-soluble vitamins, a human study and an animal experiment were conducted. In the human study, the 24-h urinary excretion of water-soluble vitamins in 12 healthy Japanese adults fasting for a day was measured. One-day fasting drastically decreased urinary thiamin content to 30%, and increased urinary riboflavin content by 3-fold. Other water-soluble vitamin contents did not show significant change by fasting. To further investigate the alterations of water-soluble vitamin status by starvation, rats were starved for 3 d, and water-soluble vitamin contents in the liver, blood and urine were measured during starvation. Urinary excretion of thiamin, riboflavin, vitamin B(6) metabolite 4-pyridoxic acid, nicotinamide metabolites and folate decreased during starvation, but that of vitamin B(12), pantothenic acid and biotin did not. As for blood vitamin levels, only blood vitamin B(1), plasma PLP and plasma folate levels decreased with starvation. All water-soluble vitamin contents in the liver decreased during starvation, whereas vitamin concentrations in the liver did not decrease. Starvation decreased only concentrations of vitamin B(12) and folate in the skeletal muscle. These results suggest that water-soluble vitamins were released from the liver, and supplied to the peripheral tissues to maintain vitamin nutrition. Our human study also suggested that the effect of fasting should be taken into consideration for subjects showing low urinary thiamin and high urinary riboflavin.

Tetraphenylborate Solubility in High Ionic Strength Salt Solutions

International Nuclear Information System (INIS)

Serkiz, S.M.; Ginn, J.D.; Jurgensen, A.R.

1998-04-01

Solubility of sodium and potassium salts of the tetraphenylborate ion (TPB) in simulated Savannah River Site High Level Waste was investigated. Data generated from this study allow more accurate predictions of TPB solubility at the In-Tank Precipitation (ITP) facility. Because previous research showed large deviations in the observed solubility of TPB salts when compared with model predictions, additional data were generated to better understand the solubility of TPB in more complex systems of high ionic strength and those containing both potassium and sodium. These data allow evaluation of the ability of current models to accurately predict equilibrium TPB concentrations over the range of experimental conditions investigated in this study

Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

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Dudhipala, Narendar; Veerabrahma, Kishan

2017-02-01

Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

Investigation of Changes in Solubility Values of Some Non Impregnated Pine Species used in Water Cooling Towers

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Murat ÖZALP

2007-01-01

Full Text Available Scotch pine (Pinus sylvestris L., Austrian black pine (Pinus nigra L. and Cyprus pine (Pinus brutia L. specimens were prepared and settled to water return system on water cooling tower. For every 3 months period’s specimens were tested solubility of hot and could water, 1% NaOH, alcohol-benzene and ethyl alcohol values were determined. For the control specimens significant color change, odour and surface softening was observed. For chemical analysis, all the solubility values were changed significantly.

Utilization of water soluble plastics for radiological control within nuclear power plants

International Nuclear Information System (INIS)

Smith, R.J.; Deltete, C.P.; Homyk, W.A.; Kasprzak, L.; Robinson, P.J.

1989-01-01

The utilization of plastic products for radioactive contamination control within nuclear power facilities currently results in relatively large volumes of waste requiring disposal as low-level radioactive waste. The utilization of a polymer resin product that possesses comparable physical attributes to currently utilized plastic materials, but which is water soluble, has significant potential to reduce the volume of plastic waste requiring disposal as radwaste. Such a volume reduction will reduce overall plant )ampersand M costs, reduce the overall waste volume allocation utilization, and improve the regulatory perception of any plant realizing a volume reduction through plastic source minimization. This potential reduction in waste volume (and associated availability of the Low-level Waste Policy Amendments Act disposal allocation for other purposes), combined with potential economic benefits summarized above, has led to the undertaking of a detailed evaluation, presented in this paper

Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

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Dajun D. Sun

2014-02-01

Full Text Available Water-insoluble materials containing amorphous solid dispersions (ASD are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate (PHEMA can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

Science.gov (United States)

Sun, Dajun D; Lee, Ping I

2014-02-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

Modeling carbon dioxide sequestration in saline aquifers: Significance of elevated pressures and salinities

International Nuclear Information System (INIS)

Allen, D.E.; Strazisar, B.R.; Soong, Y.; Hedges, S.W.

2005-01-01

The ultimate capacity of saline formations to sequester carbon dioxide by solubility and mineral trapping must be determined by simulating sequestration with geochemical models. These models, however, are only as reliable as the data and reaction scheme on which they are based. Several models have been used to make estimates of carbon dioxide solubility and mineral formation as a function of pressure and fluid composition. Intercomparison of modeling results indicates that failure to adjust all equilibrium constants to account for elevated carbon dioxide pressures results in significant errors in both solubility and mineral formation estimates. Absence of experimental data at high carbon dioxide pressures and high salinities make verification of model results difficult. Results indicate standalone solubility models that do not take mineral reactions into account will underestimate the total capacity of aquifers to sequester carbon dioxide in the long term through enhanced solubility and mineral trapping mechanisms. Overall, it is difficult to confidently predict the ultimate sequestration capacity of deep saline aquifers using geochemical models. (author)

Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods

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Hadidi N

2011-04-01

Full Text Available Naghmeh Hadidi1, Farzad Kobarfard2, Nastaran Nafissi-Varcheh3, Reza Aboofazeli11Department of Pharmaceutics, 2Department of Pharmaceutical Chemistry, 3Department of Pharmaceutical Biotechnology, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, IranAbstract: In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs with phospholipid-polyethylene glycols (Pl-PEGs was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution.Keywords: phospholipid-PEG, D-optimal design, loading efficiency, Raman spectroscopy, scanning electron microscopy, theromogravimetric analysis, carbon nanotubes

Analysis of chemical concepts as the basic of virtual laboratory development and process science skills in solubility and solubility product subject

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Syafrina, R.; Rohman, I.; Yuliani, G.

2018-05-01

This study aims to analyze the concept characteristics of solubility and solubility products that will serve as the basis for the development of virtual laboratory and students' science process skills. Characteristics of the analyzed concepts include concept definitions, concept attributes, and types of concepts. The concept analysis method uses concept analysis according to Herron. The results of the concept analysis show that there are twelve chemical concepts that become the prerequisite concept before studying the solubility and solubility and five core concepts that students must understand in the solubility and Solubility product. As many as 58.3% of the definitions of the concepts contained in high school textbooks support students' science process skills, the rest of the definition of the concept is memorized. Concept attributes that meet three levels of chemical representation and can be poured into a virtual laboratory have a percentage of 66.6%. Type of concept, 83.3% is a concept based on principle; and 16.6% concepts that state the process. Meanwhile, the science process skills that can be developed based on concept analysis are the ability to observe, calculate, measure, predict, interpret, hypothesize, apply, classify, and inference.

Solubility and stability of inorganic carbonates

International Nuclear Information System (INIS)

Taylor, P.

1987-01-01

The chemistry of inorganic carbonates is reviewed, with emphasis on solubility and hydrolytic stability, in order to identify candidate waste forms for immobilization and disposal of 14 C. At present, CaCO 3 and BaCO 3 are the two most widely favoured wasted forms, primarily because they are the products of proven CO 2 -scrubbing technology. However, they have relatively high solubilities in non-alkaline solutions, necessitating care in selecting and assessing an appropriate disposal environment. Three compounds with better solubility characteristics in near-neutral waters are identified: bismutite, (BiO) 2 CO 3 ; hydrocerussite, Pb 3 (OH) 2 (CO 3 ) 2 ; and rhodochrosite, MnCO 3 . Some of the limitations of each of these alternative waste forms are discussed

Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

International Nuclear Information System (INIS)

Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

1991-01-01

Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

Membrane and Soluble Apo-1 as a Marker of Apoptosis in Patients with Acute Leukaemia

International Nuclear Information System (INIS)

Abu Taleb, F.M.; El-Nemr, D.M.; Shawky, N.M.; Esh, S.S.

2002-01-01

We have planned this work to evaluate the significance and prognostic values of both membrane and soluble APO- 1 as markers of apoptosis in patients with acute leukaemia before and after chemotherapy. Methods and Materials: For that, 30 patients suffering from acute leukaemia (15 patients with ALL and 15 patients with AML) and 10 apparently healthy individuals serving as control group, were selected and subjected to the following: thorough history and clinical examination, routine investigations including: complete blood picture, bone marrow examination, cytochemistry, immuno phenotyping of the blast cells and specific investigations including: detection of mAPO-1 (CD95) on surface of blast cells by flow cytometry, detection of DNA fragmentation by agarose gel electrophoresis and measurement of soluble APO- 1 by ELISA technique before and after chemotherapy. Results: Surface membrane CD95 was found to be expressed on the majority of ALL blast cells (86.6%) and in only 60% of AML blast cells. The degree of surface membrane expression was variable ranging from 23-86% in ALL and from 43-89% in AML. In both ALL and AML patients, a significant relationship was detected between surface CD95 expression and response to initial induction chemotherapy. Ninety-one percent of ALL patients and 84% of AML patients who had surface CD95 expression> 20% on their blast cells showed complete hematological remission after initial induction chemotherapy. This was confirmed by finding that DNA extracted from patients under chemotherapy, whose blast cells CD95 expression was > 20%, showed DNA fragmentation (DNA laddering) by agarose gel electrophoresis (characteristic of apoptosis). As regards soluble CD95 (SCD95) before starting chemotherapy, no statistically significant difference was observed between the level of soluble CD95 in both ALL and AML patients and the control group ((ρ > 0.05). But, in AML patients, the level of soluble CD95 tended to be elevated (not significantly) in

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

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Sun J

2012-11-01

Full Text Available Jiao Sun,1 Fan Wang,1,2 Yue Sui,1 Zhennan She,1 Wenjun Zhai,1 Chunling Wang,1 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 2Beijing Zhijianjinrui Applied Pharmaceutical Science Inc, Beijing, ChinaAbstract: In this paper work, four naked nanocrystals (size range 80–700 nm were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.Keywords: particle size, solubility, dissolution, nanocrystal, bioavailability, coenzyme Q10

Mineral contents and their solubility on calcium carbonat calcite nanocrystals from cockle shell powder (Anadara granosa Linn)

Science.gov (United States)

Widyastuti, S.; Pramushinta, I. A.

2018-03-01

Prepared and characterized calcium carbonat calcite nanocrystals improves solubility. Calcium carbonat calcite nanocrystals were synthesized using precipitation method from the waste of blood clam cockle shells (Anadara granosa Linn). This study was conducted to analyze mineral composition of nanocrystals calcium carbonat calcite cockle (Anadara granosa) shell for calcium fortification of food applications and to evaluate the solubilities of Calsium and Phospor. The sample of nanocrystals from cockle shells was evaluated to determine the content of 11 macro-and micro-elements. These elements are Calcium (Ca), Magnesium (Mg), Sodium (Na), Phosphorus (P), Potassium (K), Ferrum (Fe), Copper (Cu), Nickel (Ni), Zink (Zn), Boron (B) and Silica (Si)). Cockleshell powders were found to contain toxic elements below detectable levels. The solubilities of Calcium and Phospor were p<0.05.

Plasma soluble prion protein, a potential biomarker for sport-related concussions: a pilot study.

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Pham, Nam; Akonasu, Hungbo; Shishkin, Rhonda; Taghibiglou, Changiz

2015-01-01

Sport-related mild traumatic brain injury (mTBI) or concussion is a significant health concern to athletes with potential long-term consequences. The diagnosis of sport concussion and return to sport decision making is one of the greatest challenges facing health care clinicians working in sports. Blood biomarkers have recently demonstrated their potential in assisting the detection of brain injury particularly, in those cases with no obvious physical injury. We have recently discovered plasma soluble cellular prion protein (PrP(C)) as a potential reliable biomarker for blast induced TBI (bTBI) in a rodent animal model. In order to explore the application of this novel TBI biomarker to sport-related concussion, we conducted a pilot study at the University of Saskatchewan (U of S) by recruiting athlete and non-athlete 18 to 30 year-old students. Using a modified quantitative ELISA method, we first established normal values for the plasma soluble PrP(C) in male and female students. The measured plasma soluble PrP(C) in confirmed concussion cases demonstrated a significant elevation of this analyte in post-concussion samples. Data collected from our pilot study indicates that the plasma soluble PrP(C) is a potential biomarker for sport-related concussion, which may be further developed into a clinical diagnostic tool to assist clinicians in the assessment of sport concussion and return-to-play decision making.

Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.

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Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Servadio, Michela; Melancia, Francesca; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Cortesi, Rita; Nastruzzi, Claudio

2017-09-01

This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.

Noble gas solubility in silicate melts:a review of experimentation and theory, and implications regarding magma degassing processes

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A. Paonita

2005-06-01

Full Text Available Noble gas solubility in silicate melts and glasses has gained a crucial role in Earth Sciences investigations and in the studies of non-crystalline materials on a micro to a macro-scale. Due to their special geochemical features, noble gases are in fact ideal tracers of magma degassing. Their inert nature also allows them to be used to probe the structure of silicate melts. Owing to the development of modern high pressure and temperature technologies, a large number of experimental investigations have been performed on this subject in recent times. This paper reviews the related literature, and tries to define our present state of knowledge, the problems encountered in the experimental procedures and the theoretical questions which remain unresolved. Throughout the manuscript I will also try to show how the thermodynamic and structural interpretations of the growing experimental dataset are greatly improving our understanding of the dissolution mechanisms, although there are still several points under discussion. Our improved capability of predicting noble gas solubilities in conditions closer to those found in magma has allowed scientists to develop quantitative models of magma degassing, which provide constraints on a number of questions of geological impact. Despite these recent improvements, noble gas solubility in more complex systems involving the main volatiles in magmas, is poorly known and a lot of work must be done. Expertise from other fields would be extremely valuable to upcoming research, thus focus should be placed on the structural aspects and the practical and commercial interests of the study of noble gas solubility.

Rehearsal significantly improves immediate and delayed recall on the Rey Auditory Verbal Learning Test.

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Hessen, Erik

2011-10-01

A repeated observation during memory assessment with the Rey Auditory Verbal Learning Test (RAVLT) is that patients who spontaneously employ a memory rehearsal strategy by repeating the word list more than once achieve better scores than patients who only repeat the word list once. This observation led to concern about the ability of the standard test procedure of RAVLT and similar tests in eliciting the best possible recall scores. The purpose of the present study was to test the hypothesis that a rehearsal recall strategy of repeating the word list more than once would result in improved scores of recall on the RAVLT. We report on differences in outcome after standard administration and after experimental administration on Immediate and Delayed Recall measures from the RAVLT of 50 patients. The experimental administration resulted in significantly improved scores for all the variables employed. Additionally, it was found that patients who failed effort screening showed significantly poorer improvement on Delayed Recall compared with those who passed the effort screening. The general clear improvement both in raw scores and T-scores demonstrates that recall performance can be significantly influenced by the strategy of the patient or by small variations in instructions by the examiner.

Water-soluble resorcin[4]arene based cavitands

NARCIS (Netherlands)

Grote gansey, M.H.B.; Grote Gansey, Marcel H.B.; Bakker, Frank K.G.; Feiters, Martinus C.; Geurts, Hubertus P.M.; Verboom, Willem; Reinhoudt, David

1998-01-01

Water-soluble resorcin[4]arene based cavitands were obtained in good yields by reaction of bromomethylcavitands with pyridine. Their solubility was determined by conductometry. The behaviour in water depends on the alkyl chain length; the methylcavitand does not aggregate, whereas the pentyl- and

Efficient protein production method for NMR using soluble protein tags with cold shock expression vector

International Nuclear Information System (INIS)

Hayashi, Kokoro; Kojima, Chojiro

2010-01-01

The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To address these problems, a modified cold-shock expression system containing a glutathione S-transferase (GST) tag, the pCold-GST system, was investigated. The pCold-GST system successfully expressed 9 out of 10 proteins that otherwise could not be expressed using a conventional E. coli expression system. Here, we applied the pCold-GST system to 84 proteins and 78 proteins were successfully expressed in the soluble fraction. Three other cold-shock expression systems containing a maltose binding protein tag (pCold-MBP), protein G B1 domain tag (pCold-GB1) or thioredoxin tag (pCold-Trx) were also developed to improve the yield. Additionally, we show that a C-terminal proline tag, which is invisible in 1 H- 15 N HSQC spectra, inhibits protein degradation and increases the final yield of unstable proteins. The purified proteins were amenable to NMR analyses. These data suggest that pCold expression systems combined with soluble protein tags can be utilized to improve the expression and purification of various proteins for NMR analysis.

Encapsulation of solid dispersion in solid lipid particles for dissolution enhancement of poorly water-soluble drug.

Science.gov (United States)

Tran, Khanh Thi My; Vo, Toi Van; Tran, Phuong Ha-Lien; Lee, Beom-Jin; Duan, Wei; Tran, Thao Truong-Dinh

2017-06-05

The aim of this research was to engineer solid dispersion lipid particles (SD-SLs) in which a solid dispersion (SD) was encapsulated to form the core of solid lipid particles (SLs), thereby achieving an efficient enhancement in the dissolution of a poorly water-soluble drug. Ultrasonication was introduced into the process to obtain micro/nanoscale SLs. The mechanism of dissolution enhancement was investigated by analysing the crystalline structure, molecular interactions, and particle size of the formulations. The drug release from the SD-SLs was significantly greater than that from the SD or SLs alone. This enhancement in drug release was dependent on the preparation method and the drug-to-polymer ratio of the SD. With an appropriate amount of polymer in the SD, the solidification method had the potential to alter the drug crystallinity to an amorphous state, resulting in particle uniformity and molecular interactions in the SD-SLs. The proposed system provides a new strategy for enhancing the dissolution rate of poorly water-soluble drugs and further improving their bioavailability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Determination of water-soluble vitamins using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium salts.

Science.gov (United States)

Tsukatani, Tadayuki; Suenaga, Hikaru; Ishiyama, Munetaka; Ezoe, Takatoshi; Matsumoto, Kiyoshi

2011-07-15

A method for the determination of water-soluble vitamins using a colorimetric microbial viability assay based on the reduction of the tetrazolium salt {2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8)} via 2-methyl-1,4-napthoquinone (NQ) was developed. Measurement conditions were optimized for the microbiological determination of water-soluble vitamins, such as vitamin B(6), biotin, folic acid, niacin, and pantothenic acid, using microorganisms that have a water-soluble vitamin requirement. A linear relationship between absorbance and water-soluble vitamin concentration was obtained. The proposed method was applied to determine the concentration of vitamin B(6) in various foodstuffs. There was good agreement between vitamin B(6) concentrations determined after 24h using the WST-8 colorimetric method and those obtained after 48h using a conventional method. The results suggest that the WST-8 colorimetric assay is a useful method for the rapid determination of water-soluble vitamins in a 96-well microtiter plate. Copyright © 2011 Elsevier Ltd. All rights reserved.

The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

Science.gov (United States)

Brasil, Girlandia Alexandre; Silva-Cutini, Mirian de Almeida; Moraes, Flávia de Souza Andrade; Pereira, Thiago de Melo Costa; Vasquez, Elisardo Corral; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Lima, Ewelyne Miranda; Biancardi, Vinícia Campana; Maia, June Ferreira; de Andrade, Tadeu Uggere

We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP 50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP 50 , the lower plateau, and HR range. In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio. Copyright © 2018 Elsevier Inc. All rights reserved.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

Science.gov (United States)

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone.

Science.gov (United States)

Piras, Anna Maria; Zambito, Ylenia; Burgalassi, Susi; Monti, Daniela; Tampucci, Silvia; Terreni, Eleonora; Fabiano, Angela; Balzano, Federica; Uccello-Barretta, Gloria; Chetoni, Patrizia

2018-03-30

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

Role of alkaline endonucleases in the release of soluble chromatin from thymus, spleen and liver nuclei of normal and irradiated mice

International Nuclear Information System (INIS)

Suciu, D.

1979-01-01

Thymus, spleen and liver nuclei released a large fraction of soluble chromatin in vitro when incubation was carried out in sucrose media containing low concentrations of CaCl 2 and/or MgCl 2 . A significant fraction of deoxyribopolynucleotides (DPN) was also extracted from nuclei. After 30 min of incubation at 37 0 C, the maximum release of soluble chromatin was observed near a pH of 8, which corresponds to the optimum pH of the alkaline endonuclease activity from thymus, spleen and liver. The soluble chromatin and DPN were precipitated by increasing the bivalent ion concentration of the medium. The protein/DNA ratio and the molecular weight of DNA suggest that the soluble chromatin and DPN represent nucleosome-like particles. The release of soluble chromatin in the first 4 hours of incubation was significantly increased if the nuclear fraction was isolated from the thymus and spleen of whole-body irradiated mice (1000 rad). This effect was absent in the liver nuclei. (author)

Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement.

Science.gov (United States)

Li, Xin; Yuan, Huiling; Zhang, Caiyun; Chen, Weidong; Cheng, Weiye; Chen, Xin; Ye, Xi

2016-08-01

We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur. Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated. Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution. The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application. © 2016 Royal Pharmaceutical Society.

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

40 CFR Table 7 to Subpart Vvvvvv... - Partially Soluble HAP

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 14 2010-07-01 2010-07-01 false Partially Soluble HAP 7 Table 7 to... Pt. 63, Subpt. VVVVVV, Table 7 Table 7 to Subpart VVVVVV of Part 63—Partially Soluble HAP As required... partially soluble HAP listed in the following table. Partially soluble HAP name CAS No. 1. 1,1,1...

Enhanced Iron Solubility at Low pH in Global Aerosols

Directory of Open Access Journals (Sweden)

Ellery D. Ingall

2018-05-01

Full Text Available The composition and oxidation state of aerosol iron were examined using synchrotron-based iron near-edge X-ray absorption spectroscopy. By combining synchrotron-based techniques with water leachate analysis, impacts of oxidation state and mineralogy on aerosol iron solubility were assessed for samples taken from multiple locations in the Southern and the Atlantic Oceans; and also from Noida (India, Bermuda, and the Eastern Mediterranean (Crete. These sampling locations capture iron-containing aerosols from different source regions with varying marine, mineral dust, and anthropogenic influences. Across all locations, pH had the dominating influence on aerosol iron solubility. When aerosol samples were approximately neutral pH, iron solubility was on average 3.4%; when samples were below pH 4, the iron solubility increased to 35%. This observed aerosol iron solubility profile is consistent with thermodynamic predictions for the solubility of Fe(III oxides, the major iron containing phase in the aerosol samples. Source regions and transport paths were also important factors affecting iron solubility, as samples originating from or passing over populated regions tended to contain more soluble iron. Although the acidity appears to affect aerosol iron solubility globally, a direct relationship for all samples is confounded by factors such as anthropogenic influence, aerosol buffer capacity, mineralogy and physical processes.

Solubility of Gliclazide and Ion-Molecular Interactions with Aminopropanol in Aqueous Solutions

Science.gov (United States)

Hamdan, Imad I.; El-Sabawi, Dina; Abu-Dahab, Rana

2018-01-01

A new salt of gliclazide (GZD) was prepared and was shown to have a significantly higher aqueous solubility at physiological pH together with superior dissolution profiles in comparison to GZD employing an organic amino-alcohol base. Characterization by NMR, IR, DSC, conductometry and HPLC techniques concluded that an ion pair salt is formed between acidic GZD and basic aminopropanol (AMP). In addition to the presence of about 5% tightly bound water, hydrogen bonds appeared to form extensively between GZD, AMP and water molecules. Unlike many of solubility enhancing approaches, the salt did not hamper the permeability of GZD as shown by transport through Caco-2 cells model. In vivo studies on rats confirmed that the blood glucose lowering effect of GZD-AMP was significantly higher and more rapid compared to parent GZD indicating an enhanced overall performance of the prepared salt.

Spider Silk Fibers Spun from Soluble Recombinant Silk Produced in Mammalian Cells

Science.gov (United States)

Lazaris, Anthoula; Arcidiacono, Steven; Huang, Yue; Zhou, Jiang-Feng; Duguay, François; Chretien, Nathalie; Welsh, Elizabeth A.; Soares, Jason W.; Karatzas, Costas N.

2002-01-01

Spider silks are protein-based ``biopolymer'' filaments or threads secreted by specialized epithelial cells as concentrated soluble precursors of highly repetitive primary sequences. Spider dragline silk is a flexible, lightweight fiber of extraordinary strength and toughness comparable to that of synthetic high-performance fibers. We sought to ``biomimic'' the process of spider silk production by expressing in mammalian cells the dragline silk genes (ADF-3/MaSpII and MaSpI) of two spider species. We produced soluble recombinant (rc)-dragline silk proteins with molecular masses of 60 to 140 kilodaltons. We demonstrated the wet spinning of silk monofilaments spun from a concentrated aqueous solution of soluble rc-spider silk protein (ADF-3; 60 kilodaltons) under modest shear and coagulation conditions. The spun fibers were water insoluble with a fine diameter (10 to 40 micrometers) and exhibited toughness and modulus values comparable to those of native dragline silks but with lower tenacity. Dope solutions with rc-silk protein concentrations >20% and postspinning draw were necessary to achieve improved mechanical properties of the spun fibers. Fiber properties correlated with finer fiber diameter and increased birefringence.

Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates.

Science.gov (United States)

Alam, Mohd Aftab; Ali, Raisuddin; Al-Jenoobi, Fahad Ibrahim; Al-Mohizea, Abdullah M

2012-11-01

Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs. The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize(™), closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug-carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, Solumer(TM) used to prepare stable amorphous SD. Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.

PEPTIDE SOLUBILITY, STRUCTURE AND CHARGE POSITION EFFECT ON ADSORPTION BY ALUMINIUM HYDROXIDE

Directory of Open Access Journals (Sweden)

Mary Trujillo

2008-04-01

Full Text Available Solubility, structure and position of charges in a peptide antigen sequence can be mentioned as being amongst the basic features of adsorption. In order to study their effect on adsorption, seven analogue series were synthesized from a MSP-1 peptide sequence by systematically replacing each one of the positions in the peptide sequence by aspartic acid, glutamic acid, serine, alanine, asparagine, glutamine or lysine. Such modifications in analogue peptide sequences showed a non-regular tendency regarding solubility and adsorption data. Aspartic acid and Glutamic acid analogue series showed great improvements in adsorption, especially in peptides where Lysine in position 6 and Arginine in position 13 were replaced. Solubility of position 5 analogue was greater than the position 6 analogue in Aspartic acid series; however, the position 6 analogue showed best adsorption results whilst the Aspartic acid in position 5 analogue showed no adsorption in the same conditions. Nuclear Magnetic Resonance structural analysis revealed differences in the -helical structureextension between these analogues. The Aspartic acid in position 6, located in the polar side of the helix, may allow this analogueto fit better onto the adsorption regions suggesting that the local electrostatic charge is responsible for this behavior.

Effect of supplementation of water-soluble vitamins on oxidative stress and blood pressure in prehypertensives.

Science.gov (United States)

Talikoti, Prashanth; Bobby, Zachariah; Hamide, Abdoul

2015-01-01

The objective of the study was to evaluate the effect of water-soluble vitamins on oxidative stress and blood pressure in prehypertensives. Sixty prehypertensives were recruited and randomized into 2 groups of 30 each. One group received water-soluble vitamins and the other placebo for 4 months. Further increase in blood pressure was not observed in the vitamin group which increased significantly in the placebo group at the end of 4 months. Malonedialdehyde and protein carbonylation were reduced during the course of treatment with vitamins whereas in the placebo group there was an increase in the level of malondialdehyde. In conclusion, supplementation of water-soluble vitamins in prehypertension reduces oxidative stress and its progression to hypertension.

Solubility Part 1

NARCIS (Netherlands)

Tantra, Ratna; Bolea, Eduardo; Bouwmeester, H.; Rey-Castro, Carlos; David, C.A.A.; Dogné, Jean Michel; Laborda, Francisco; Laloy, Julie; Robinson, Kenneth N.; Undas, A.K.; Zande, van der M.

2016-01-01

This chapter gives an overview of different methods that can potentially be used to determine the solubility of nanomaterials. In general, the methods presented can be broadly divided into four categories: separation methods, methods to quantify free ions, methods to quantify total dissolved

Molybdenum solubility in aluminium nitrate solutions

Energy Technology Data Exchange (ETDEWEB)

Heres, X.; Sans, D.; Bertrand, M.; Eysseric, C. [CEA, Centre de Marcoule, Nuclear Energy Division, DRCP, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Brackx, E.; Domenger, R.; Excoffier, E. [CEA, Centre de Marcoule, Nuclear Energy Division, DTEC, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Valery, J.F. [AREVA-NC, DOR/RDP, Paris - La Defense (France)

2016-07-01

For over 60 years, research reactors (RR or RTR for research testing reactors) have been used as neutron sources for research, radioisotope production ({sup 99}Mo/{sup 99m}Tc), nuclear medicine, materials characterization, etc... Currently, over 240 of these reactors are in operation in 56 countries. They are simpler than power reactors and operate at lower temperature (cooled to below 100 C. degrees). The fuel assemblies are typically plates or cylinders of uranium alloy and aluminium (U-Al) coated with pure aluminium. These fuels can be processed in AREVA La Hague plant after batch dissolution in concentrated nitric acid and mixing with UOX fuel streams. The aim of this study is to accurately measure the solubility of molybdenum in nitric acid solution containing high concentrations of aluminium. The higher the molybdenum solubility is, the more flexible reprocessing operations are, especially when the spent fuels contain high amounts of molybdenum. To be most representative of the dissolution process, uranium-molybdenum alloy and molybdenum metal powder were dissolved in solutions of aluminium nitrate at the nominal dissolution temperature. The experiments showed complete dissolution of metallic elements after 30 minutes long stirring, even if molybdenum metal was added in excess. After an induction period, a slow precipitation of molybdic acid occurs for about 15 hours. The data obtained show the molybdenum solubility decreases with increasing aluminium concentration. The solubility law follows an exponential relation around 40 g/L of aluminium with a high determination coefficient. Molybdenum solubility is not impacted by the presence of gadolinium, or by an increasing concentration of uranium. (authors)