Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000

The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG.

Anion dopant effects on the structure and performance of polyethersulfone membranes

In this work, the effect of various casting solution salt dopants with similar cations, but different anions: (NaPO3)(6), Na2SO4, Na2CO3, NaCl, and NaF, on the morphology and performance of polyethersulfone ultrafiltration membranes was evaluated. The phase inversion process was used to produce all membranes using an 18% polyethersulfone in n-methylpyrrolidone casting solution and water as the non-solvent. Scanning electron microscopy (SEM) images of the membrane cross-section and surface pores were used to determine the specific anion effects on membrane morphology. The SEM images depicted significant changes to the membrane internal structure and pore size with respect to the type and concentration of the casting solution anion dopant. Membrane permeability, molecular weight cut-off, alginate retention, and susceptibility to fouling were evaluated using ultrapure water dead-end and ultrapure water, aqueous polyethylene glycol, aqueous sodium alginate, and natural surface water cross-flow filtration tests. Among the anions evaluated, hexametaphosphate doped at 1% w/w to the polymer resulted in the membrane with highest dead-end permeability at 490 LMH-bar (2- to 3-fold greater than the control), greatest alginate retention at 96.5%, and lowest susceptibility to fouling. The significant increase in membrane performance indicates that the hexametaphosphate anion has great potential to be used as a membrane casting solution dopant. It was also clearly demonstrated that membrane pore morphological characteristics can be effectively used to predict drinking water treatment performance. (C) 2012 Elsevier B.V. All rights reserved.

A stable liquid-liquid extraction system for clavulanic acid using polymer-based aqueous two-phase systems

The partitioning of Clavulanic Acid (CA) in a novel inexpensive and stable aqueous two-phase system (ATPS) composed by poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) has been studied. The aqueous two-phase systems are formed by mixing both polymers with a salt (NaCl or Na2SO4) and an aqueous solution of CA. The stability of CA on the presence of both polymers was investigated and it was observed that these polymers do not degrade the biomolecule. The effect of PEG-molecular size, polymer concentrations on the commercial CA partitioning has been studied, at 25 degrees C. The data showed that commercial CA was preferentially partitioned for the PEG-rich phase with a partition coefficient (K-CA) between 1 and 12 in the PEG/NaPA aqueous two phase systems supplemented with NaCl and Na2SO4. The partition to the PEG phase was increased in the systems with high polymer concentrations. Furthermore, Na2SO4 caused higher CA preference for the PEG-phase than NaCl. The systems having a composition with 10 wt.% of PEG4000, 20 wt.% of NaPA8000 and 6 wt.% of Na2SO4 were selected as the optimal ones in terms of recovery of CA from fermented broth of Streptomyces clavuligerus. The partitioning results (K-CA = 9.15 +/- 1.06) are competitive with commercial extraction methods of CA (K-CA = 11.91 +/- 2.08) which emphasizes that the system PEG/NaPA/Na2SO4 can be used as a new process to CA purification/concentration from fermented broth. (C) 2012 Elsevier B.V. All rights reserved.

Chemical characterization and in vitro biological activity of four tropical legumes, Styzolobium aterrimum L., Styzolobium deeringianum, Leucaena leucocephala, and Mimosa caesalpiniaefolia, as compared with a tropical grass, Cynodon spp. for the use in ruminant diets

Leucaena leucocephala (LEU) and three under-utilized tanniferous legumes, Styzolobium aterrimum L. (STA), Styzolobium deeringianum (STD), and Mimosa caesalpiniaefolia Benth (MIC) were chemically characterized and the biological activity of tannins was evaluated using in vitro simulated ruminal fermentation through tannin-binding polyethylene glycol (PEG) and compared with a non-tanniferous tropical grass hay, Cynodon spp. (CYN). The Hohenheim gas test was used and gas production (GP) was recorded at 4, 8, 12, 24, 32, 48, 56, 72, 80, and 96 h incubation with and without PEG. Kinetic parameters were estimated by an exponential model. STA, STD, and LEU contained higher (P < 0.05) crude protein than MIC, which had greater neutral detergent fibre and acid detergent fibre. Total phenols, total tannins, and condensed tannins (CT) were consistently the highest in MIC. Gas production was the lowest from MIC (P < 0.05) and the highest in LEU and STA. MIC + PEG largely reduced (P < 0.05) the lag phase and the fractional rate of fermentation and increased potential GP. Kinetic parameters of STA + PEG and LEU + PEG were not affected. LEU + PEG produced greater gas increment (P < 0.05) than STD + PEG, although both legumes had the same CT. All legumes except MIC were more extensively degraded than CYN. However, fermentation of the legumes was differently affected by the presence and proportions of CT, indigestible fibre or both.

The Effects of Palmitic Acid on Nitric Oxide Production by Rat Skeletal Muscle: Mechanism via Superoxide and iNOS Activation

Background: Increased plasma concentrations of free fatty acids (FFA) can lead to insulin resistance in skeletal muscle, impaired effects on mitochondrial function, including uncoupling of oxidative phosphorylation and decrease of endogenous antioxidant defenses. Nitric oxide (NO) is a highly diffusible gas that presents a half-life of 5-10 seconds and is involved in several physiological and pathological conditions. The effects of palmitic acid on nitric oxide (NO) production by rat skeletal muscle cells and the possible mechanism involved were investigated. Methods: Primary cultured rat skeletal muscle cells were treated with palmitic acid and NO production was assessed by nitrite measurement (Griess method) and 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Nuclear factor-kappa B (NF-kappa B) activation was evaluated by electrophoretic mobility shift assay and iNOS protein content by western blotting. Results: Palmitic acid treatment increased nitric oxide production. This effect was abolished by treatment with NOS inhibitors, L-nitro-arginine (LNA) and L-nitro-arginine methyl esther (L-NAME). NF-kappa B activation and iNOS content were increased due to palmitic acid treatment. The participation of superoxide on nitric oxide production was investigated by incubating the cells with DAF-2-DA in the presence or absence of palmitic acid, a superoxide generator system (X-XO), a mixture of NOS inhibitors and SOD-PEG (superoxide dismutase linked to polyethylene glycol). Palmitic acid and X-XO system increased NO production and this effect was abolished when cells were treated with NOS inhibitors and also with SOD-PEG. Conclusions: In summary, palmitic acid stimulates NO production in cultured skeletal muscle cells through production of superoxide, nuclear factor-kappa B activation and increase of iNOS protein content. Copyright (C) 2012 S. Karger AG, Basel

Effect of partial preferential orientation and distortions in octahedral clusters on the photoluminescence properties of FeWO4 nanocrystals

This communication is a report of our initial research to obtain iron tungstate (FeWO4) nanocrystals by the microwave-hydrothermal method at 170 degrees C for 45 min. X-ray diffraction patterns showed that the FeWO4 nanocrystals prepared with polyethylene glycol-200 have a partial preferential orientation in the (011) plane in relation to other nanocrystals prepared with sodium bis(2-ethylhexyl) sulfosuccinate and water. Rietveld refinement data indicates that all nanocrystals are monophasic with wolframite-type monoclinic structures and exhibit different distortions on octahedral [FeO6]/[WO6] clusters. High resolution transmission electron microcopy revealed an oriented attachment mechanism for the growth of aggregated FeWO4 nanocrystals. Finally, we observed that the photoluminescence properties of these nanocrystals are affected by partial preferential orientation in the (011) plane and distortions on [FeO6]/[WO6] clusters.

Spray Congealing of Pharmaceuticals: Study on Production of Solid Dispersions Using Box-Behnken Design

This work aimed at evaluating the spray congealing method for the production of microparticles of carbamazepine combined with a polyoxylglyceride carrier. In addition, the influence of the spray congealing conditions on the improvement of drug solubility was investigated using a three-factor, three-level Box-Behnken design. The factors studied were the cooling air flow rate, atomizing pressure, and molten dispersion feed rate. Dependent variables were the yield, solubility, encapsulation efficiency, particle size, water activity, and flow properties. Statistical analysis showed that only the yield was affected by the factors studied. The characteristics of the microparticles were evaluated using X-ray powder diffraction, scanning electron microscopy, differential scanning calorimetry, and hot-stage microscopy. The results showed a spherical morphology and changes in the crystalline state of the drug. The microparticles were obtained with good yields and encapsulation efficiencies, which ranged from 50 to 80% and 99.5 to 112%, respectively. The average size of the microparticles ranged from 17.7 to 39.4 mu m, the water activities were always below 0.5, and flowability was good to moderate. Both the solubility and dissolution rate of carbamazepine from the spray congealed microparticles were remarkably improved. The carbamazepine solubility showed a threefold increase and dissolution profile showed a twofold increase after 60 min compared to the raw drug. The Box-Behnken fractional factorial design proved to be a powerful tool to identify the best conditions for the manufacture of solid dispersion microparticles by spray congealing.

Solid Dispersion of Ursolic Acid in Gelucire 50/13: a Strategy to Enhance Drug Release and Trypanocidal Activity

Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 mu g/mL in PMs to 293.43 mu g/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.

Microstructured ternary solid dispersions to improve carbamazepine solubility

The aim of this study was to investigate the improvement of the aqueous solubility of carbamazepine by preparing microstructured ternary solid dispersions using polyoxylglycerides and colloidal silicon dioxide. Microstructured solid dispersions were obtained in a spray dryer. The influence of the spray drying conditions on the properties of the microparticles was investigated using a full 3(2) factorial design in which the factors studied were the silicon dioxide content and the air outlet temperature. The microparticles were thoroughly characterized in terms of yield, solubility, angle of repose, particle size, drug content, moisture content, sorption isotherms, morphology, thermal behavior, infrared spectroscopy and crystallinity. The dissolution rates of carbamazepine and of the microparticles in water were also determined. In general, the microstructured solid dispersions demonstrated good yield, adequate flow and moisture content (<3%), drug recovery (91.98 to 100.22%) and particle size (<142.90 mu m). Thermal and infrared analysis showed that there was no drug interaction during the process. On the other hand, the results of X-ray diffraction evidenced a partial polymorphic modification of carbamazepine. The solubility and dissolution rates of carbamazepine were remarkably improved. Therefore, the results confirm the high potential of the spray drying technique to obtain microstructured ternary solid dispersions. (C) 2011 Elsevier B.V. All rights reserved.

Hydric restriction as vigor assessment method of soybean seeds

The objective of this study was to investigate the possibility of using hydric restriction as a method for evaluating vigor of soybean seeds. The soybean seeds, cultivar BRS 245RR, represented by four different seed lots, were characterized by germination and vigor. For the treatment of hydric restriction and temperature, the combination of substrate water potential and temperature were the following: deionized water (0.0 MPa); polyethylene glycol (PEG 6000) aqueous solution (-0.1, -0.3 and -0.5 MPa); and four temperatures (20 ºC, 25 ºC, 30 ºC, and 35 ºC), respectively. A completely randomized experimental design was used, with four replications per treatment, and the ANOVA was performed individually for each combination of temperature and water potential of substrate. According to results obtained, the test of hydric restriction has the same efficiency of the accelerated aging test in estimating vigor of soybean seeds, cv. BRS 245RR, when water potentials of -0.1 MPa or -0.3 MPa at a temperature of 25 ºC, or -0.3 MPa at a temperature of 30 ºC are used.

The impact of the alkali cation on the mechanism of the electro-oxidation of ethylene glycol on Pt

By means of in situ IR spectroscopy we investigate the effect of dissolved alkali cations on the electro-oxidation of ethylene glycol on platinum in alkaline media. The results revealed that the increase in the oxidation currents (Li(+) < Na(+) < K(+)) is reflected in the increase in the ratio between carbonate and oxalate produced.

Plasmid DNA partitioning and separation using poly(ethylene glycol)/poly(acrylate)/salt aqueous two-phase systems

Phase diagrams of poly(ethylene glycol)/polyacrylate/Na2SO4 systems have been investigated with respect to polymer size and pH. Plasmid DNA from Escherichia coil can depending on pH and polymer molecular weight be directed to a poly(ethylene glycol) or to a polyacrylate-rich phase in an aqueous two-phase system formed by these polymers. Bovine serum albumin (BSA) and E. coil homogenate proteins can be directed opposite to the plasmid partitioning in these systems. Two bioseparation processes have been developed where in the final step the pDNA is partitioned to a salt-rich phase giving a total process yield of 60-70%. In one of them the pDNA is partitioned between the polyacrylate and PEG-phases in order to remove proteins. In a more simplified process the plasmid is partitioned to a PEG-phase and back-extracted into a Na2SO4-rich phase. The novel polyacrylate/PEG system allows a strong change of the partitioning between the phases with relatively small changes in composition or pH. (C) 2012 Elsevier B.V. All rights reserved.

Production of Fructooligosaccharides by Aspergillus phoenicis Biofilm on Polyethylene as Inert Support

Aspergillus phoenicis biofilms on polyethylene as inert support were used to produce fructooligosaccharides (FOS) in media containing 25% (m/V) of sucrose as a carbon source. The maximum production of total FOS (122 mg/mL), with 68% of 1-kestose and 32% of nystose, was obtained in Khanna medium maintained at 30 degrees C for 48 h under orbital agitation (100 rpm). At high concentrations of sucrose (30%, m/V), the recovery of FOS was higher than that observed at a low concentration (5%, m/V). High levels of FOS (242 mg/mL) were also recovered when using the biofilm in sodium acetate buffer with high sucrose concentration (50%, m/V) for 10 h. When the dried biofilm was reused in a fresh culture medium, there was a recovery of approx. 13.7% of total FOS after 72 h of cultivation at 30 C, and 10% corresponded to 1-kestose. The biofilm morphology, analyzed by scanning electron microscope, revealed a noncompact mycelium structure, with unfilled spaces and channels present among the hyphae. The results obtained in this study show that A. phoenicis biofilms may find application for FOS production in a single-step fermentation process, which is cost-effective in terms of reusability, downstream processing and efficiency.

Effect of pulse repetition rate and number of pulses in the analysis of polypropylene and high density polyethylene by nanosecond infrared laser induced breakdown spectroscopy

Pulse repetition rates and the number of laser pulses are among the most important parameters that do affect the analysis of solid materials by laser induced breakdown spectroscopy, and the knowledge of their effects is of fundamental importance for suggesting analytical strategies when dealing with laser ablation processes of polymers. In this contribution, the influence of these parameters in the ablated mass and in the features of craters was evaluated in polypropylene and high density polyethylene plates containing pigment-based PbCrO4. Surface characterization and craters profile were carried out by perfilometry and scanning electron microscopy. Area, volume and profile of craters were obtained using Taylor Map software. A laser induced breakdown spectroscopy system consisted of a Q-Switched Nd:YAG laser (1064 nm, 5 ns) and an Echelle spectrometer equipped with ICCD detector were used. The evaluated operating conditions consisted of 10, 25 and 50 laser pulses at 1, 5 and 10 Hz, 250 mJ/pulse (85 J cm(-2)), 2 mu s delay time and 6 mu s integration time gate. Differences in the topographical features among craters of both polymers were observed. The decrease in the repetition rate resulted in irregular craters and formation of edges, especially in polypropylene sample. The differences in the topographical features and ablated masses were attributed to the influence of the degree of crystallinity, crystalline melting temperature and glass transition temperature in the ablation process of the high density polyethylene and polypropylene. It was also observed that the intensities of chromium and lead emission signals obtained at 10 Hz were two times higher than at 5 Hz by keeping the number of laser pulses constant. (C) 2011 Elsevier B. V. All rights reserved.

Evaluation of the propylene glycol association on some physical and chemical properties of mineral trioxide aggregate

Duarte MAH, Alves de Aguiar K, Zeferino MA, Vivan RR, Ordinola-Zapata R, Tanomaru-Filho M, Weckwerth PH, Kuga MC. Evaluation of the propylene glycol association on some physical and chemical properties of mineral trioxide aggregate. International Endodontic Journal, 45, 565570, 2012. Abstract Aim To evaluate the influence of propylene glycol (PG) on the flowability, setting time, pH and calcium ion release of mineral trioxide aggregate (MTA). Methodology Mineral trioxide aggregate was mixed with different proportions of PG, as follows: group 1: MTA + 100% distilled water (DW); group 2: MTA + 80% DW and 20% PG; group 3: MTA + 50% DW and 50% PG; group 4: MTA + 20% DW and 80% PG; group 5: MTA + 100% PG. The ANSI/ADA No. 57 was followed for evaluating the flowability and the setting time was measured by using ASTM C266-08. For pH and calcium release analyses, 50 acrylic teeth with root-end cavities were filled with the materials (n = 10) and individually immersed in flasks containing 10 mL deionized water. After 3 h, 24 h, 72 h and 168 h, teeth were placed in new flasks and the water in which each specimen was immersed had its pH determined by a pH metre and the calcium release measured by an atomic absorption spectrophotometer with a calcium-specific hollow cathode lamp. Data were analysed by using one-way anova test for global comparison and by using Tukeys test for individual comparisons. Results The highest value of flowability was observed with MTA + 20% DW and 80% PG and the lowest values were found with MTA + 100% DW. They were significantly different compared to the other groups (P < 0.05). The presence of PG did not affect the pH and calcium release. The MTA + 100% PG favoured the highest (P < 0.05) pH and calcium release after 3 h. Increasing the PG proportion interfered (P < 0.05) with the setting time; when used at the volume of 100% setting did not occur. Conclusion The addition of PG to MTA-Angelus increased its setting time, improved flowability and increased the pH and calcium ion release during the initial post-mixing periods. The ratio of 80% DW 20% PG is recommended.